A Study to Evaluate the Safety, Tolerability, and Efficacy of Long-Term Gantenerumab Administration in Participants With Alzheimer's Disease (AD)

Alzheimer Disease Clinical Trial

Official title:

An Open-Label, Multicenter, Rollover Study to Evaluate the Safety, Tolerability, and Efficacy of Long-Term Gantenerumab Administration in Participants With Alzheimer's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04374253
• Other study ID #: WN42171
• Secondary ID: 2020-000766-42
• Status: Terminated
• Phase: Phase 3
• Start date: January 26, 2021
• Est. completion date: March 6, 2023

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter, rollover study to evaluate the safety, tolerability, and efficacy of long-term administration of open-label gantenerumab in participants with AD who completed Study WN29922 or WN39658, either the double-blind or open-label extension (OLE) part.

Description:

Participants who were in the active arm in the double blind part and those who have completed OLE part in the parent study, will continue receive open-label gantenerumab 510 mg sub-cutaneously (SC) every 2 weeks (Q2W). Participants who are naive to gantenerumab treatment will be required to undergo the 3 step uptitration scheme as in the parent study before receiving target dose of open label gantenerumab.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1382
• Est. completion date: March 6, 2023
• Est. primary completion date: March 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Completed Study WN29922 or WN39658, either its double-blind part or OLE part, and did not discontinue study drug early

• The participant should be capable of completing assessments either alone or with the help of the caregiver

• Availability of a person (referred to as the "caregiver")

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception methods with a failure rate of <1% per year (bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices) during the treatment period and for at least 16 weeks after the final dose of gantenerumab

• Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug

Exclusion Criteria:

• Pregnant or breastfeeding, or intending to become pregnant during the study or within at least 16 weeks after the final dose of study drug

• Prematurely discontinued from Study WN29922 or WN39658

• Any medical condition that may jeopardize the participant's safety if he or she continues to receive study treatment

• Received any investigational treatment other than gantenerumab during or since completion of Study WN29922 or WN39658, either its double-blind or OLE part

• Evidence of disseminated leptomeningeal hemosiderosis

• Evidence of intracerebral macrohemorrhage

• Use of prohibited medication

• Evidence of ARIA-E on the last MRI scan report in Study WN29922 or WN39658, either its double-blind or OLE part

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Gantenerumab
Group 1 participants who were in the active arm in the double blind part in the parent study (WN29922 or WN39658), will continue to receive open-label gantenerumab 510 mg SC, Q2W. Participants who are naive to gantenerumab treatment will be required to undergo the 3 step uptitration scheme before receiving target dose of open label gantenerumab, 510 mg SC, Q2W.
• Gantenerumab
Group 2 participants who have completed OLE part in the parent study (WN29922 or WN39658), will continue to receive open-label gantenerumab 510 mg SC, Q2W

Locations

Country	Name	City	State
Argentina	Hospital Italiano	Caba
Argentina	Universidad Maimonides	Caba
Argentina	Instituto Geriatrico Nuestra Señora de las Nieves	Capital Federal
Argentina	CEN Centro Especializado en Neurociencias	Cordoba
Argentina	Instituto Kremer	Córdoba
Argentina	Instituto de Neurociencias San Agustín S.A.	La Plata
Argentina	Fundación Scherbovsky; General Department	Mendoza
Australia	St Vincent's Hospital Sydney; Neurology	Darlinghurst	New South Wales
Australia	Central Coast Neurosciences Research	Erina	New South Wales
Australia	Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre	Heidelberg West	Victoria
Australia	Southern Neurology	Kogarah	New South Wales
Australia	Australian Alzheimer's Research Foundation	Nedlands	Western Australia
Australia	The Queen Elizabeth Hospital; Neurology	Woodville	South Australia
Belgium	AZ Sint Blasius (Dendermonde)	Dendermonde
Belgium	UZ Gent	Gent
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Brazil	Hospital Nossa Senhora das Graças; Setor de Pesquisa em Neurologia	Curitiba	PR
Brazil	Instituto de Neurologia de Curitiba	Curitiba	PR
Brazil	Clinica Clinilive ltda	Maringa	PR
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital das Clinicas - FMUSP_X; Neurologia	Sao Paulo	SP
Canada	Center for Diagnosis and Research on Alzheimer's disease	Greenfield Park	Quebec
Canada	Parkwood Hospital; Geriatric Medicine	London	Ontario
Canada	Alpha Recherche Clinique	Quebec
Canada	Baycrest Health Sciences	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	The Medical Arts Health Research Group - West Vancouver	Vancouver	British Columbia
Canada	Devonshire Clinical Research	Woodstock	Ontario
Chile	Psicomed Estudios Médicos	Antofagasta
Chile	Biomedica Research Group	Santiago
Chile	Especialidades Medicas LYS	Santiago
China	Beijing Tian Tan Hospital,Capital Medical University	Beijing City
Denmark	Aarhus Universitetshospital; Neurologisk Afd. F, Demensklinikken	Aarhus N
Denmark	Rigshospitalet, Hukommelsesklinikken	København Ø
Denmark	Svendborg Sygehus; Neurologisk afdeling N, Demensklinik Fyn	Svendborg
Finland	Terveystalo Ruoholahti	Helsinki
Finland	Itä-Suomen yliopisto, Kuopion kampus	Kuopio
France	CHU Amiens Hopital Sud; Neurologie	Amiens Cedex1
France	Hôpital Avicenne; Centre de Recherche Clinique	Bobigny Cedex
France	Groupement Hospitalier Est - Hôpital Neurologique; Neurologie A (U502)	Bron cedex
France	CHU de la Timone - Hopital d Adultes; Service de Neurologie	Marseille
France	Hôpital Lariboisière	Paris
France	CHU Poitiers - Hopital La Miletrie	Poitiers
France	CHU Strasbourg Hôpital Hautepierre	Strasbourg
France	Gerontopole; Centre de Recherche clinique	Toulouse
France	Hopital des Charpennes	Villeurbanne
Germany	Ambulates Gesundheitszentrum der Charité GmbH; MVZ Neurologie Campus Benjamin Franklin	Berlin
Germany	ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic	Berlin
Germany	Universitätsklinikum Köln; Klinik und Poliklinik für Psychiatrie und Psychotherapie	Köln
Germany	PANAKEIA - Arzneimittelforschung Leipzig GmbH	Leipzig
Germany	Universitätsmedizin derJohannes Gutenberg-Universität Mainz;Klinik für Psychiatrie und Psychotherapi	Mainz
Germany	Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie	München
Germany	Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie	Münster
Germany	Universitätsklinikum Rostock Zentrum für Nervenheilkunde	Rostock
Germany	Universitätsklinikum Ulm; Klinik für Neurologie	Ulm
Germany	Studienzentrum Nordwest Dr med Joachim Springub Herr Wolfgang Schwarz	Westerstede
Germany	Forschungszentrum Ruhr	Witten
Hungary	Semmelweis University; Department of Neurology	Budapest
Italy	IRCCS ?Centro S. Giovanni di Dio? Fatebenefratelli -UO Alzheimer	Brescia	Lombardia
Italy	IRCCS Ospedale San Raffaele; Centro Disturbi della Memoria	Milano	Lombardia
Italy	Nuovo Ospedale Civile S. Agostino-Estense; Clinica Neurologica ? Dipartimento di Neuroscienze	Modena	Emilia-Romagna
Italy	ASST DI MONZA; Neurologia	Monza	Lombardia
Italy	Dipartimento delle Patologie Emergenti; Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo	Sicilia
Italy	IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA	Pozzilli	Molise
Italy	Fondazione Santa Lucia IRCCS; Neurologia e Riabilitazione Neurologica	Roma	Lazio
Italy	Ospedale San Giovanni Calibita Fatebenefratell;Neurologia	Roma	Lazio
Italy	Umberto I Policlinico di Roma-Università di Roma La Sapienza	Roma	Lazio
Italy	AO Città della Salute e della Scienza Osp.S.Giov.Battista Molinette; SC Geriatria	Torino	Piemonte
Japan	Nagoya Ekisaikai Hospital	Aichi
Japan	National Center for Geriatrics and Gerontology	Aichi
Japan	Yachiyo Hospital	Aichi
Japan	Inage Neurology and Memory Clinic	Chiba
Japan	Juntendo University Urayasu Hospital	Chiba
Japan	Medical Corporation Hakuyokai Kashiwado Hospital	Chiba
Japan	Tokyo Bay Advanced Medical and Makuhari Clinic	Chiba
Japan	Fukuoka University Hospital	Fukuoka
Japan	Southern Tohoku Medical Clinic	Fukushima
Japan	National Hospital Organization Hiroshima-Nishi Medical Center	Hiroshima
Japan	Hyogo Prefectural HarimaHimeji General Medical Center	Hyogo
Japan	Kobe University Hospital	Hyogo
Japan	Matsui Dietary and Dementia Clinic	Hyogo
Japan	Tsukazaki Hospital	Hyogo
Japan	Kagawa Prefectural Central Hospital	Kagawa
Japan	Shonan Kamakura General Hospital	Kanagawa
Japan	Rakuwakai Otowa Hospital	Kyoto
Japan	Uji Takeda Hospital	Kyoto
Japan	Okayama Kyokuto Hospital	Okayama
Japan	Rijikai Medical Corporation Katayama Medical Clinic	Okayama
Japan	Kishiwada Tokushukai Hospital	Osaka
Japan	MI Clinic	Osaka
Japan	National Hospital Organization Hizen Psychiatric Medical Center	Saga
Japan	NHO Shizuoka Institute of Epilepsy and Neurological Disorders	Shizuoka
Japan	Shizuoka City Shimizu Hospital	Shizuoka
Japan	Jichiidai Station Brain Clinic	Tochigi
Japan	Medical corporation Ichiekai Itsuki Hospital	Tokushima
Japan	Tokushima Hospital	Tokushima
Japan	National Center of Neurology and Psychiatry	Tokyo
Japan	Nozomi Memory Clinic	Tokyo
Japan	P-One Clinic	Tokyo
Japan	Tokyo Medical and Dental University Hospital	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Japan	Yamagata Tokusyukai Hospital	Yamagata
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Myongji Hospital	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Ewha Womans University Hospital (Seoul)	Seoul
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Lithuania	Vilnius University Hospital Santariskiu Clinics; Neurology	Vilnius
Mexico	Mexico Centre for Clinical Research	Ciudad de México	Mexico CITY (federal District)
Mexico	Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC	Culiacán	Sinaloa
Mexico	AVIX Investigación Clínica S.C	Monterrey	Nuevo LEON
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez UANL; Depto.de NeurologíaPta.BajaConsulta	Monterrey	Nuevo LEON
Netherlands	Brain Research Center B.V	Amsterdam
Peru	Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion	Bellavista
Peru	Clinica Internacional; Unidad De Investigacion	Lima
Peru	Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia	Lima
Poland	O?rodek Badawczo-Naukowo-Dydaktyczny Chorób Ot?piennych w ?cinawie	?cinawa
Poland	Podlaskie Centrum Psychogeriatrii	Bia?ystok
Poland	NZOZ Vitamed	Bydgoszcz
Poland	NEURO-CARE Sp. z o.o. Sp. Komandytowa	Katowice
Poland	KO-MED Centra Kliniczne Lublin II	Lublin
Poland	Neurologiczny NZOZ Centrum Leczenia SM; Osrodek Badan Klinicznych	Plewiska
Poland	Senior Sp. Z O.O. Poradnia Psychogeriatryczna	Sopot
Poland	mMED Maciej Czarnecki	Warszawa
Poland	Pratia S.A.	Warszawa
Poland	NZOZ WCA	Wroc?aw
Portugal	Hospital de Braga; Servico de Neurologia	Braga
Portugal	HUC; Servico de Neurologia	Coimbra
Portugal	Hospital da Senhora da Oliveira-Guimarães; Serviço de Neurologia	Guimarães
Portugal	Hospital Geral de Santo Antonio; Servico de Neurologia	Porto
Puerto Rico	Santa Cruz Behavioral PSC	Bayamon
Puerto Rico	University of Puerto Rico - Medical Science Campus; Internal Medicine	San Juan
Russian Federation	State autonomous institution of healthcare Inter-regional clinical and diagnostic center	Kazan	Tatarstan
Russian Federation	Vertebronevrologiya LLC	Kazan	Tatarstan
Russian Federation	FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency	Krasnoyarsk	Krasnojarsk
Russian Federation	City Clin Hosp n.a. S.P.Botkin	Moscow	Moskovskaja Oblast
Russian Federation	University ?linic of headaches	Moscow	Moskovskaja Oblast
Russian Federation	City Polyclinic No. 2 of the Department of Healthcare of the City of Moscow	Moskva	Moskovskaja Oblast
Russian Federation	FSBMEI HPE "Military Medical Academy n.a. S.M. Kirov" of the MoD of the RF	Sankt-peterburg	Sankt Petersburg
Russian Federation	MHI City Clinical Hospital #2 named after V.I. Razumovsky; Psychiatric	Saratov
Russian Federation	Nebbiolo Center for Clinical Trials	Tomsk
Spain	Hospital General Universitario de Albacete; Servicio de Neurología	Albacete
Spain	Fundación ACE; Servicio de Neurología	Barcelona
Spain	Hospital Clinic i Provincial; Servicio de Neurologia	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia	Barcelona
Spain	Hospital del Mar; Servicio de Neurologia	Barcelona
Spain	Hospital Vall d'Hebron; Servicio de Neurología	Barcelona
Spain	Hospital Universitario Reina Sofia; Servicio de Neurologia	Cordoba
Spain	Policlínica Guipuzcoa; Servicio de Neurología	Donostia-san Sebastian	Guipuzcoa
Spain	Hospital General Universitario de Elche; Servicio de Neurología	Elche	Alicante
Spain	CAE OROITU; Servicio de Neurología	Getxo	Vizcaya
Spain	Hospital Universitari de Bellvitge; Servicio de Neurologia	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario de Santa Maria; Servicio de Neurología	Lleida	Lerida
Spain	Hospital San Pedro; Servicio de Neurología	Logroño	LA Rioja
Spain	Hospital Ramon y Cajal; Servicio de Neurologia	Madrid
Spain	Hospital Ruber Internacional; Servicio de Neurología	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Neurologia	Madrid
Spain	Universitario de La Princesa; Servicio de Neurología	Madrid
Spain	HM Universitario Puerta del Sur CINAC (C.Integ.Neuroc);; Servicio de Psiquiatría	Móstoles	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
Spain	Clinica Universitaria de Navarra; Servicio de Neurología	Pamplona	Navarra
Spain	Hospital Virgen del Puerto. Servicio de Neurología	Plasencia	Caceres
Spain	Hospital Quiron de Madrid; Servicio de Neurologia	Pozuelo de Alarcon	Madrid
Spain	Complejo Asistencial Universitario de Salamanca; Servicio de Psiquiatría	Salamanca
Spain	Hospital General De Catalunya; Servicio de Neurologia	Sant Cugat del Valles	Barcelona
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Neurología	SANtander	Cantabria
Spain	Hospital Victoria Eugenia; Servico Neurología	Sevilla
Spain	Hospital Virgen del Rocío; Servicio de Neurología	Sevilla
Spain	Hospital Mutua De Terrasa; Servicio de Neurologia	Terrassa	Barcelona
Spain	Hospital Universitario Dr. Peset; Servicio de Neurologia	Valencia
Spain	Hospital Universitario la Fe; Servicio de Neurologia	Valencia
Spain	Complejo Asistencial de Zamora; Servicio Psiquiatria	Zamora
Spain	Servicio de Neurología Hospital Viamed Montecanal.	Zaragoza
Sweden	Skånes Universitetssjukhus Malmö, Minneskliniken	Malmö
Sweden	Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry	Mölndal
Sweden	KAROLINSKA UNI HOSPITAL, HUDDINGE; Mottagning Kognitiv Forskning, M54	Stockholm
Taiwan	Changhua Christian Hospital; Neurology	Changhua County
Taiwan	Kaohsiung Medical University Hospital; Neurology	Kaohsiung
Taiwan	Chang Gung Memorial Foundation - Kaohsiung - Neurology	Niaosong Dist.
Taiwan	China Medical University Hospital; Neurology	North Dist.
Taiwan	National Taiwan University Hospital; Neurology	Taipei
Taiwan	Chang Gung Memorial Foundation - Linkou - Neurology	Taoyuan
Turkey	Ondokuz Mayis Univ. Med. Fac.; Neurology	Samsun
United Kingdom	The Rice Centre; Royal United Hospital	Bath
United Kingdom	Re:Cognition Health Birmingham	Birmingham
United Kingdom	The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre	Cheltenham
United Kingdom	Surrey and Borders NHS Foundation Trust; Research and Development Department	Chertsey
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Queen Elizabeth University Hospital - PPDS	Glasgow
United Kingdom	Charing Cross Hospital	London
United Kingdom	Re:Cognition Health London	London
United Kingdom	St George?s Hospital	London
United Kingdom	Campus for Ageing and Vitality	Newcastle
United Kingdom	Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	University Southampton NHS Foundation Trust; Wessex Neurologica Centre	Southampton
United States	Abington Neurological Associates	Abington	Pennsylvania
United States	Emory University	Atlanta	Georgia
United States	JEM Research LLC	Atlantis	Florida
United States	Senior Adults Specialty Research	Austin	Texas
United States	American Health Network Institute, LLC	Avon	Indiana
United States	Missouri Memory Center	Bolivar	Missouri
United States	Brigham and Womens Hospital; Center for Alzheimer Research & Treatment	Boston	Massachusetts
United States	Accel Research Sites - CRU Tampa	Bradenton	Florida
United States	Bradenton Research Center	Bradenton	Florida
United States	Behavioral Health Research	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Cleveland Clinic; Cleveland Lou Ruvo Center for Brain Health ? Neurological Institute	Cleveland	Ohio
United States	Ohio State University; College of Medicine	Columbus	Ohio
United States	Kerwin Medical Center	Dallas	Texas
United States	Neurology Consultants of Dallas; Research Department	Dallas	Texas
United States	Brain Matters Research, Inc.	Delray Beach	Florida
United States	Health Initiatives Research, PLLC	Fayetteville	Arkansas
United States	Precise Research Centers	Flowood	Mississippi
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	Fullerton Neurology and Headache Center	Fullerton	California
United States	Neurology Center of North Orange County	Fullerton	California
United States	Center for Advanced Research & Education	Gainesville	Georgia
United States	Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine	Houston	Texas
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Irvine Center for Clinical Research	Irvine	California
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania
United States	Neurological Associates of Long Island, PC	Lake Success	New York
United States	Cleveland Clinic Lou Ruvo; Center for Brain Research	Las Vegas	Nevada
United States	UW Wisconsin-Madison	Madison	Wisconsin
United States	ClinCloud, LLC	Maitland	Florida
United States	Alzheimer's Memory Center	Matthews	North Carolina
United States	Allied Biomedical Research Institute, Inc	Miami	Florida
United States	Optimus U Corp	Miami	Florida
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Boston Center for Memory	Newton	Massachusetts
United States	Sentara Neurology Specialists	Norfolk	Virginia
United States	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut
United States	Renstar Medical Research	Ocala	Florida
United States	University of Nebraska Medical Center; Dept of Neurological Sciences	Omaha	Nebraska
United States	Banner Alzheimer?s Institute	Phoenix	Arizona
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Summit Research Network Inc.	Portland	Oregon
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Desert Valley Research	Redlands	California
United States	National Clinical Research Inc.-Richmond	Richmond	Virginia
United States	AD-CARE, University of Rochester Medical Center	Rochester	New York
United States	Sutter Medical Group, Neurology	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Wasatch Clinical Research, LLC	Salt Lake City	Utah
United States	Syrentis Clinical Research	Santa Ana	California
United States	Intercoastal Medical Group	Sarasota	Florida
United States	California Neuroscience Research Medical Group, Inc	Sherman Oaks	California
United States	Southern California Research LLC	Simi Valley	California
United States	Southern Illinois University, School of Medicine	Springfield	Illinois
United States	The Cognitive and Research Center of New Jersey	Springfield	New Jersey
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Banner Sun Health Research Insitute	Sun City	Arizona
United States	Infinity Clinical Research, LLC	Sunrise	Florida
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	Advanced Memory Research Institute of NJ	Toms River	New Jersey
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Alzheimer?s Research and Treatment Center	Wellington	Florida
United States	Via Christi Research	Wichita	Kansas
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  Denmark,  Finland,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Lithuania,  Mexico,  Netherlands,  Peru,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With at Least One Adverse Event (AE) and Serious Adverse Event (SAE)	An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of casual attribution. A SAE is any AE that is fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug or a significant medical event in the investigator's judgment. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Primary	Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) Score	C-SSRS= assesses lifetime suicidality of participant (at baseline) & any new instances of suicidality (since last visit). Structured interview prompts recollection of suicidal ideation (intensity of ideation, behavior, & attempts with actual/potential lethality). Categories have yes/no responses, include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted/Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior= "yes" to any of listed categories. Score of 0= no suicide risk. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here. First dosing visit in OLE (first dosing in current study or OLE period of parent GRADUATE studies)=baseline (OLE Day 1).	From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Primary	Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by MRI	ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. In ARIA-E, (E for oedema or effusion), oedema can be seen in different areas of the brain on MRI, representing fluid leakage into the brain parenchyma or sulcal spaces. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Primary	Number of Participants With at Least One Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by MRI	ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. ARIA-H (H for hemosiderosis) are small foci of signal loss observed on MRI sequences sensitive for paramagnetic tissue properties and comprise cerebral microbleeds (small foci of bleeding in the brain parenchyma) and leptomeningeal hemosiderosis (small foci of bleeding on the surface of the brain). These changes also occur sporadically in AD. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Primary	Number of Participants With Injection-Site Reactions (ISRs)	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, regardless of casual attribution. Local injection reactions (or injection site reactions) are defined as AEs related to the injection site that occur during or within 24 hours after study drug administration that are judged to be related to the study drug injection. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Primary	Number of Participants Who Discontinued the Study Due an AE	An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of casual attribution. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Primary	Number of Participants With at Least One Adverse Event of Special Interest (AESI)	An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of casual attribution. AEs that were considered to be of special interest for this study included cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law and suspected transmission of an infectious agent by the study drug. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)
Secondary	Change From Baseline Over Time in Clinical Dementia Rating - Global Score (CDR-GS)	CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=normal, 0.5=very mild dementia, 1=mild dementia, 2=moderate dementia, and 3= severe dementia. The score range for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Secondary	Change From Baseline Over Time in Clinical Dementia Rating (CDR) - Sum of Boxes (SB)	CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=no impairment, 0.5=questionable impairment, and 1, 2, and 3=mild, moderate, and severe impairment, respectively. The CDR-SB is based on summing each of the domain box scores with total score ranging from 0-18 with higher scores reflecting greater cognitive and functional impairment. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Secondary	Change From Baseline Over Time in Mini-Mental State Examination (MMSE) Score	MMSE is a rater-administered performance-based outcome (PerfO) that includes a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. The questions target six areas: orientation, registration, attention, short-term recall, language, and constructional praxis/visuospatial abilities. Total score ranges from 0-30, with lower scores indicating greater impairment. A positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Secondary	Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 11 (ADAS-Cog11) Score	ADAS-Cog11 was designed to measure cognitive symptom change in participants with Alzheimer's Disease (AD) and consisted of 11 tasks. The standard 11 items (and corresponding score range) were: word recall (0-10), commands (0-5), constructional praxis (0-5), naming objects and fingers (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), spoken language ability (0-5), comprehension of spoken language (0-5), word-finding difficulty (0-5), and remembering test instructions (0-5). The test included 7 performance items and 4 clinician-rated items. The ADAS-Cog11 total score was the sum of all 11 individual items, with a total score ranging from 0 (no impairment) to 70 (severe impairment). Higher scores indicated more severe cognitive impairment. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Secondary	Change From Baseline Over Time in Alzheimer Disease Assessment Scale-Cognition, Subscale 13 (ADAS-Cog13) Score	The ADAS-Cog13 total score includes all of the items in the ADAS-Cog11 in addition to delayed word recall and the number cancellation. For the ADAS-cog 13 the range is 0-85 (score range for Delayed Word Recall [DWR] score is 0-10 and for Number Cancellation [NC] is 0-5, thus the score is ADAS-cog 11[0-70] plus the scores for DWR and NC). A higher score indicates worse performance. A negative change from baseline indicates improvement in cognitive function. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Secondary	Change From Baseline Over Time in Verbal Fluency Task Score	VFT is a rater administered PerfO that measures speed and flexibility of verbal thought with a total score that ranges from 0-99 (lower scores indicating lower performance). A positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Secondary	Change From Baseline Over Time in Coding (Digit Symbol Substitution Test [DSST]) Subset	Coding, also called DSST is a rater administered PerfO that measures speed of processing and associative memory with a total score that ranges from 0-135 (lower scores indicating lower performance). The DSST was adapted from the Wechsler Adult Intelligence Scale. The 120-second version of the test was used in this study. Positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Secondary	Change in Functional Activities Questionnaire (FAQ) Score	FAQ is a rater-administered observer-reported outcome (ObsRO) (informant-based measure) that measures a participant's functional ability to perform complex higher-order activities. The observer provides performance ratings of the target person on ten complex higher-order activities. Total score that ranges from 0-30, with higher scores reflecting greater functional impairment. A negative change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Secondary	Change in Alzheimer Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) Score	ADCS-ADL is a 23-item rater-administered, ObsRO that captures a participant's ability to perform basic activities of daily living (e.g., eating and toileting) and more complex ADL or instrumental activities of daily living (iADL, e.g., using the telephone, managing finances, preparing a meal). Total score ranges from 0-78, with higher scores reflecting better functioning. A positive change from baseline indicates improvement. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	Baseline (OLE Day 1), Weeks 24, 36, 52, 76 and 104
Secondary	Number of Participants With Anti-drug Antibody (ADA) to Gantenerumab	The number of participants with positive results for ADA against gantenerumab at any of the post-baseline assessment time-points were reported. Evaluable participant during OLE was participant with an ADA assay result from at least one sample during OLE. Treatment Emergent ADA = A participant with a negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. The first dosing visit in the OLE (first dosing in current study or first dosing in the OLE period of the parent GRADUATE studies) was considered as baseline (OLE Day 1).	From Baseline (OLE Day 1) up to 14 weeks after the last dose (up to 134 weeks)