A Long-Term Safety And Tolerability Extension Study Of Bapineuzumab In Alzheimer Disease Patients

Alzheimer Disease Clinical Trial

Official title:

A Phase 3 Extension, Multicenter, Long Term Safety And Tolerability Trial Of Bapineuzumab (Aab 001, Eln115727) In Subjects With Alzheimer Disease Who Are Apolipoprotein E 4 Carriers And Participated In Study 3133k1-3001-us Or Study 3133k1-3001-ww.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00998764
• Other study ID #: 3133K1-3003
• Secondary ID: B25210042009-015
• Status: Terminated
• Phase: Phase 3
• First received: October 16, 2009
• Last updated: November 30, 2015
• Start date: December 2009
• Est. completion date: November 2012

Study information

• Verified date: November 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the long-term safety and tolerability of bapineuzumab in subjects with Alzheimer Disease who participated in study 3133K1-3001(NCT00676143). Over 250 sites will participate in over 26 countries. Subjects will receive bapineuzumab. Each subject's participation will last approximately 4 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 494
• Est. completion date: November 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 51 Years to 90 Years

Eligibility

Inclusion Criteria:

• Subject has completed study 3133K1-3001 (Week 78) and brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of Alzheimer Disease

• Mini-Mental Status Examination (MMSE) >=10 at screening

• Caregiver able to attend all clinic visits with subject

Exclusion Criteria:

• Any medical or psychiatric contraindication or clinically significant abnormality that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of the study or could preclude the evaluation of the subject's response.

• Any significant brain MRI abnormality.

• Use of any investigational drugs or devices, other than bapineuzumab within the last 60 days prior to screening

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Bapineuzumab 0.5 mg/kg
I.V., 0.5 mg/kg, infusion every 13 weeks for a total of 16 infusions.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Australia	Royal Adelaide Memory Trials Centre	Adelaide	South Australia
Australia	Gosford Hospital; Pharmacy Dept	Gosford	New South Wales
Australia	Heidelberg Repatriation Hospital	Heidelberg West	Victoria
Australia	Hornsby Hospital	Hornsby	New South Wales
Australia	Hollywood Hospital; Pharmacy Dept	Nedlands	Western Australia
Australia	The McCusker Foundation for Alzheimer's Disease Research	Nedlands	Western Australia
Australia	Memory Unit 5C, Department of Neurology	Woodville South	South Australia
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Belgium	ZNA Middelheim	Antwerpen
Belgium	AZ Sint-Jan Brugge-Oostende AV	Brugge
Belgium	Cliniques Universitaires St Luc	Brussels
Belgium	Universitair Ziekenhuis Gasthuisberg	Leuven
Belgium	H.-Hartziekenhuis Roeselare-Menen	Roeselare
Chile	Psicomedica Research Group	Santiago
Finland	Ita-Suomen Yliopisto	Kuopio
Finland	University of Turku/CRST	Turku
France	CHU Hôpital Pellegrin-Tripode	Bordeaux
France	Hopital Neurologique	Bron
France	CHU de Caen	Caen
France	Hôpitaux Civils de Colmar	Colmar
France	CHU de Dijon	Dijon
France	Hôpital Roger Salengro	Lille
France	Hôpital la Timone	Marseille
France	Hôpital la Timone	Marseille cedex 5
France	CHU Hôpital Gui de Chaulliac	Montpellier
France	CHU Nord - Hôpital Guillaume et René Laënnec	Nantes - Saint Herblain
France	Hôpital Cimiez	Nice
France	Hôpital Pitié-Salpétrière	Paris
France	CHU La Milétrie	Poitiers
France	C.H.U de Reims	Reims
France	CHRU Hôtel Dieu	Rennes
France	Department de Radiologie et d'Imagerie Medicale, Hopital Pontchaillou	Rennes Cedex 9
France	Centre Hospitalier Universitaire Charles Nicolle	Rouen Cedex
France	CHU Purpan - Hôpital Casselardit	Toulouse
France	Hôpital Purpan	Toulouse
Italy	Sezione di Neurologia - Dipartimento di Neuroscienze	Ancona
Italy	Dipartimento di Neuroscienze,	Catania
Italy	Fondazione IRCCS- Istituto Neurologico Carlo Besta	Milano
Italy	Unita' Operativa C - Riabilitazione Neurologica	Roma
Japan	Yachiyo Hospital	Aichi
Japan	Kashiwado Hospital	Chiba
Japan	Nippon Medical School Chiba Hokusoh Hospital	Chiba
Japan	National Hospital Organization Chiba-East Hospital	Chiba-shi
Japan	National Hospital Organization Kokura Medical Center	Fukuoka
Japan	Gunma University Hospital	Gunma
Japan	Maebashi Red Cross Hospital	Gunma
Japan	Shinozuka Hospital	Gunma
Japan	National Hospital Organization Hiroshima-nishi Medical Ctr.	Hiroshima
Japan	Kobe University Hospital	Hyogo
Japan	Kagawa University Hospital	Kagawa
Japan	Nippon Medical School Musashi Kosugi Hospital	Kanagawa
Japan	National Hospital Organization Maizuru Medical Center	Kyoto
Japan	National Hospital Organization Minami-Kyoto Hospital	Kyoto
Japan	Rakuwakai Otowa Hospital	Kyoto
Japan	National Hospital Organization Matsumoto Medical Center	Nagano
Japan	Nagoya City University Hospital	Nagoya	Aichi,
Japan	National Hospital Organization Niigata National Hospital	Niigata
Japan	National Hospital Organization Minami-Okayama Medical Center	Okayama
Japan	Okayama University Hospital	Okayama
Japan	Kansai Medical University Takii Hospital	Osaka
Japan	Osaka City University Hospital	Osaka
Japan	Juntendo Tokyo Koto Geriatric Medical Center	Tokyo
Japan	Juntendo University Hospital	Tokyo
Japan	National Hospital Organization Tokyo National Hospital	Tokyo
Japan	Tokyo Medical University Hachioji Medical Center	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Japan	Tokyo Metropolitan Health and Med. Treatment Co. Ebara Hosp	Tokyo
Netherlands	Geriatry	's-HERTOGENBOSCH
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
New Zealand	The Memory Clinic Limited	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Signet Research	Christchurch
Poland	Pallmed Spolka z o.o.	Bydgoszcz
Poland	MCD Voxel	Poznan
Poland	NZOZ Neuro-kard	Poznan
Poland	Pracownia Rezonansu Magnetycznego	Warszawa
Poland	Samodzielny Publiczny Centralny Szpital Kliniczny	Warszawa
Poland	SP ZOZ Szpital Wolski	Warszawa
Portugal	Hospital Fernando da Fonseca	Amadora	Lisboa
Portugal	Hospitais Da Universidade De Coimbra	Coimbra
Portugal	Hospital Santa Maria	Lisboa
Slovakia	Univerzitna nemocnica Bratislava	Bratislava
Slovakia	Vseobecna nemocnica Rimavska Sobota	Rimavska Sobota
South Africa	St Augustine's Medical Centre 2	Durban	Kwa Zulu Natal
South Africa	Boithuso Caregivers	Johannesburg	Gauteng
South Africa	The Osteoporosis and Memory Centre	Johannesburg	Gauteng
Spain	Clinica CIMA	Barcelona
Spain	Fundacio ACE Institut Catala de Neurociences Aplicades	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Divino Valles	Burgos
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital de la Princesa	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	CLONUS	Palma de Mallorca	Islas Baleares
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Islas Baleares
Spain	Hospital Virgen del Puerto	Plasencia	Caceres
Spain	Hospital Mutua de Terrasa	Terrasa	Barcelona
Sweden	Malmo University Hospital	Malmo
Sweden	Minnes- och geriatrikmottagningen	Uppsala
Switzerland	Memory Clinic Neuro-Psychologie Zentrum	Basel	BS
United Kingdom	MAC UK Neuroscience Ltd.	Bradford
United Kingdom	Clinical Investigation and Research Unit (CIRU)	Brighton
United Kingdom	Llandough Hospital, Universtity Hospital of Wales	Cardiff	Wales
United Kingdom	Glasgow Memory Clinic	Glasgow
United Kingdom	Memory Service North, Grenoside Grange Hospital	Grenoside	Sheffield
United Kingdom	Dept. of Neurosciences Charing Cross Hospital	London
United Kingdom	The Doctors Laboratory Ltd.	London
United Kingdom	Newcastle General Hospital	Newcastle upon Tyne
United Kingdom	Northampton General Hospital	Northampton
United Kingdom	Royal Hallamshire Hospital	Sheffield
United Kingdom	Victoria Hospital	Swindon
United Kingdom	Alliance Medical	Wakefield
United States	Abington Neurological Assoc	Abington	Pennsylvania
United States	Abington Neurological Associates	Abington	Pennsylvania
United States	Bington Memorial Hospital	Abington	Pennsylvania
United States	JEM Research LLC	Atlantis	Florida
United States	Medical Specialists of the Palm Beaches	Atlantis	Florida
United States	UAB Center for Psychiatric Medicine	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University Of Alabama at Birmingham	Birmingham	Alabama
United States	University of Alabama-Birmingham	Birmingham	Alabama
United States	Alpine Clinical Research Center, Inc.	Boulder	Colorado
United States	Associated Neurologist, PC	Boulder	Colorado
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Medical University of South Carolina Hospitals and Clinics	Charleston	South Carolina
United States	Ohio State Unviersity	Columbus	Ohio
United States	Texas Neurology, P.A.	Dallas	Texas
United States	Brain Matters Research	Delray Beach	Florida
United States	Mile High Research Center	Denver	Colorado
United States	Michigan State University	East Lansing	Michigan
United States	Michigan State University	East Lansing	Michigan
United States	Rhode Island Mood and Memory Research Institute	East Providence	Rhode Island
United States	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey
United States	Alexian Brothers Neurosciences Institute Clinical Research	Elk Grove Village	Illinois
United States	Associated Neurologists of Southern Connecticut, P.C.	Fairfield	Connecticut
United States	Dedicated Clinical Research	Goodyear	Arizona
United States	Bendheim Infusion Center, Greenwich Hospital	Greenwich	Connecticut
United States	Center for Healthy Aging, Greenwich Hospital	Greenwich	Connecticut
United States	Neurological Research Center of Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Clinical Trial Center, LLC	Jenkintown	Pennsylvania
United States	The Center for Pharmaceutical Research, P.C.	Kansas City	Missouri
United States	Lake Charles Clinical Trials	Lake Charles	Louisiana
United States	Neuroscience Research Institute, LLC	Lawrenceville	Georgia
United States	Neurostudies.net	Lawrenceville	Georgia
United States	Clinical Trials, Inc.	Little Rock	Arkansas
United States	MDR	LiverPool	New York
United States	Neurological Care of Central New York	Liverpool	New York
United States	Alzheimer's Research Corp./Merician Institute for Aging	Manchester	New Jersey
United States	Medical University of South Carolina	North Charleston	South Carolina
United States	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut
United States	Compass Research, LLC	Orlando	Florida
United States	Palm Beach Neurological Center, Advanced Research Consultants, Inc.	Palm Beach Gardens	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	Banner Good Samaritan Medical Center (Imaging	Phoenix	Arizona
United States	Hope Research Institute	Phoenix	Arizona
United States	Jeffrey S. Gitt	Phoenix	Arizona
United States	Neuroscience Research of the Berkshires	Pittsfield	Massachusetts
United States	Neurostudies, Inc	Port Charlotte	Florida
United States	Southwest Florida Infusion Care, Inc.	Port Charlotte	Florida
United States	Providence Brain Institute	Portland	Oregon
United States	Providence Brain Institute-Cognitive Assessment Clinic	Portland	Oregon
United States	Summit Research Network(Oregon) Inc.	Portland	Oregon
United States	Carolina Neuropsychological Services, Inc.	Raleigh	North Carolina
United States	Healthsouth Blue Ridge Surgery Center	Raleigh	North Carolina
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Wake Radiology Associates	Raleigh	North Carolina
United States	Innovative Clinical Trials	San Antonio	Texas
United States	Integra Clinical Research, LLC	San Antonio	Texas
United States	Inventive Infusion Solutions	San Antonio	Texas
United States	Vista Infusions	San Antonio	Texas
United States	San Francisco Clinical Research Center	San Francisco	California
United States	Roskamp Institute	Sarasota	Florida
United States	Southern Illinois University School of Medicine Department	Springfield	Illinois
United States	Springfield Neurology Associates, LLC	Springfield	Massachusetts
United States	USF Health Byrd Alzheimer's Institute	Tampa	Florida
United States	Toms River X-Ray, CT & MRI	Toms River	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Chile,  Finland,  France,  Italy,  Japan,  Netherlands,  New Zealand,  Poland,  Portugal,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Reporting a Serious Adverse Event	Safety was measured according to standard adverse event collection as described in the Adverse Event Section of the Results. Complete tables of events are provided there.	Up to Week 195	No
Secondary	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78	The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8 remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.	Base Study Baseline, Weeks 13, 26, 39, 52 and 78	No
Secondary	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8)remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.	Base Study Baseline, Weeks 13, 26, 39, 52 and 78	No
Secondary	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is "yes" and a zero score was assigned if the answer is "no". For questions answered as "not applicable", no score will be assigned. The DAD total score was calculated as the total number of questions answered as "yes" divided by the total number of questions answered as "yes" or "no", times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.	Base Study Baseline, Weeks 13, 26, 39, 52 and 78	No
Secondary	Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is "yes" and a zero score was assigned if the answer is "no". For questions answered as "not applicable", no score will be assigned. The DAD total score was calculated as the total number of questions answered as "yes" divided by the total number of questions answered as "yes" or "no", times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.	Base Study Baseline, Weeks 13, 26, 39, 52 and 78	No
Secondary	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.	Base Study Baseline, Weeks 26, 52 and 78	No
Secondary	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.	Base Study Baseline, Weeks 26, 52 and 78	No
Secondary	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.	Base Study Baseline, Weeks 6, 19, 32, 45 and 78	No
Secondary	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.	Base Study Baseline, Weeks 6, 19, 32, 45 and 78	No

External Links

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