The Efficacy and Safety of Cobitolimod in Participants With Moderate to Severe Active Left-Sided Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— CONCLUDE  

Official title:

A Randomised Double-Blind Placebo-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of Cobitolimod as an Induction and Maintenance Therapy in Participants With Moderate to Severe Active Left-Sided Ulcerative Colitis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04985968
• Other study ID #: CSUC-01/21
• Status: Terminated
• Phase: Phase 3
• Start date: November 24, 2021
• Est. completion date: December 20, 2023

Study information

• Verified date: December 2023
• Source: InDex Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the efficacy of cobitolimod treatment compared to placebo in inducing clinical remission, in participants with moderate to severe active left-sided UC and to evaluate the efficacy of cobitolimod maintenance treatment compared to placebo in inducing or maintaining clinical remission at week 52, in participants with clinical response at week 6 after induction treatment with cobitolimod.

Description:

This phase III study protocol includes an induction study for 6 weeks and a maintenance study for an additional 45 weeks.

In the induction study there will be an initial phase to explore the best dose, between cobitolimod 250 mg and cobitolimod 500 mg using adaptive design.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 171
• Est. completion date: December 20, 2023
• Est. primary completion date: December 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria Induction:

• Male or female = 18 years of age.

• Established diagnosis of UC.

• Moderate to severe active left-sided UC assessed by central reading.

• Have inadequate response, loss of response or be intolerant of at least one of the following treatments: Oral GCS, AZA/6-MP, Biologics, JAK-inhibitors, or other approved advanced therapies for UC.

• Allowed to receive a therapeutic dose of the following UC drugs during the study: Oral GCS therapy (=20 mg prednisone or equivalent/day) , Oral 5-ASA/SP compounds, AZA/6-MP.

• Ability to understand the treatment, willingness to comply with all study requirements, and ability to provide informed consent.

Exclusion Criteria Induction:

• Suspicion of differential diagnosis.

• Acute fulminant UC and/or signs of systemic toxicity.

• UC limited to the rectum or extending beyond the splenic flexure.

• Have failed treatment with more than three advanced therapies of two different therapeutic classes.

• Have had surgery for treatment of UC.

• History of malignancy, unless treated with no relapse of the disease and = 5 years since last treatment (cured).

• History or presence of any clinically significant disorder.

• Concomitant treatment with cyclosporine, methotrexate, tacrolimus, or advanced therapies or similar immunosuppressants and immunomodulators.

• Treatment with rectal GCS, 5-ASA/SP or tacrolimus.

• Long-term treatment (>14 days) with antibiotics or NSAIDs .

• Serious known active infection including history of latent or active tuberculosis.

• Gastrointestinal infections including positive Clostridium difficile stool assay.

• Females who are lactating or have a positive serum pregnancy test.

• Women of childbearing potential not using highly effective contraceptive methods.

• Concurrent participation in another clinical study.

• Previous exposure to cobitolimod.

Inclusion Criteria Maintenance:

• Participants are eligible to be included in the maintenance study if they have achieved clinical response at week 6 and have adhered to the protocol procedures of the induction study.

Exclusion Criteria Maintenance:

• Participants will not be eligible for the maintenance study if they are not willing to comply with all further study requirements.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Cobitolimod 250 mg
Rectal administration
• Cobitolimod 500 mg
Rectal administration
• Placebo
Rectal administration

Locations

Country	Name	City	State
Australia	Monash Health	Clayton
Australia	St Vincent's Hospital Melbourne	Fitzroy
Australia	The Alfred Hospital	Melbourne
Australia	Royal Melbourne Hospital	Parkville
Australia	Mater Health Services	South Brisbane
Australia	Princess Alexandra Hospital	Woolloongabba
Austria	MedUn Innsbruck	Innsbruck
Austria	LKH Klagenfurt	Klagenfurt
Austria	Universitätsklinikum Salzburg	Salzburg
Austria	Akh Wien	Wien
Belgium	UZ Antwerpen	Antwerpen
Belgium	Imelda Ziekenhuis	Bonheiden
Belgium	Erasme University Hospital	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	AZ Groeninge - Campus Kennedylaan	Kortrijk
Belgium	AZ Delta	Roeselare
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska - Gastroenterology	Banja Luka
Bosnia and Herzegovina	The University Hospital Foca	Foca
Bosnia and Herzegovina	Clinical Center University of Sarajevo - Gastroenterology	Sarajevo
Bosnia and Herzegovina	General Hospital "Prim.dr.Abdulah Nakas"	Sarajevo
Bosnia and Herzegovina	Polyclinic Dr. Al-Tawil	Sarajevo
Bosnia and Herzegovina	Opca Bolnica Tesanj	Tesanj
Bosnia and Herzegovina	Plava Medical Group	Tuzla
Bosnia and Herzegovina	Cantonal Hospital Zenica	Zenica
Brazil	Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda	Goiania
Brazil	Hospital de Clinicas de Porto Alegre - Centro de Pesquisa Clinica	Porto Alegre
Brazil	Ufrj - Hospital Universitario Clementino Fraga Filho	Rio De Janeiro
Brazil	Praxis Pesquisa Medica	Santo Andre
Brazil	CEMEC - Centro Multidisciplinar de Estudos Clinicos	São Bernardo do Campo
Brazil	Kaiser Clinica	Sao Jose do Rio Preto
Canada	MUMC - Hamilton Health Sciences	Hamilton
Canada	Installation Hospital Maisonneuve-Rosemont	Montréal
Canada	Royal University Hospital	Saskatoon
Croatia	Opca bolnica Bjelovar	Bjelovar
Croatia	Clinical Hospital Osijek	Osijek
Croatia	Opca bolnica Pula	Pula
Croatia	Zadar General Hospital	Zadar
Croatia	Poliklinika Solmed	Zagreb
Croatia	University Hospital Centre Zagreb	Zagreb
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Herlev Hospital	Herlev
Denmark	Hillerod Hospital	Hillerød
Denmark	Lillebælt Hospital Vejle	Vejle
France	CHRU de Lille - Hôpital Claude Huriez	Lille
France	CHRU Montpellier-Hopital Saint Eloi - Hepato-gastro-enterologie	Montpellier
France	CHU de Nancy Brabois	Nancy
France	CHU de Nice - Hôpital de l'Archet II - Gastro-Entérologie, Hépatologie	Nice
France	Hopital Bichat - Gastroenterology	Paris
France	Hopital Saint Antoine	Paris Cedex 12
France	Centre Hospitalier Lyon Sud	Pierre Benite Cedex
France	Centre Hospitalier Universitaire de Poitiers	Poitiers
France	CHU de Saint Etienne, Hôpital Nord - Service de Gastroentérologie	Saint-Étienne
France	CHU Amiens - Hopital Sud - Service Hepato-Gastroenterolog	Salouel
France	Centre Hospitalier Universitaire de Toulouse - Hopital Rangueil	Toulouse
Georgia	JSC " Evex Hospitals"	Batumi
Georgia	LTD Israel-Georgian Medical Research Clinic Helsicore	Tiflis
Germany	Universitätsklinikum Augsburg	Augsburg
Germany	Charité - Universitätsmedizin Berlin KöR	Berlin
Germany	University Hospital Cologne AöR	Cologne
Germany	MVZ Sanaklinikum Duisburg	Duisburg
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Agaplesion Markus Krankenhaus	Frankfurt am main
Germany	Klinikum der Johann Wolfgang Goethe-Universität - Medizinische Klinik I	Frankfurt am Main
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Uniklinik Halle (Saale)	Halle
Germany	Gastroenterology Outpatient Clinic Prof. Dr. med. Ehehalt	Heidelberg
Germany	University Hospital Schleswig-Holstein	Kiel
Germany	Universitätsmedizin Mannheim	Mannheim
Germany	Medius Klinik Nürtingen	Nürtingen
Germany	Universitätsklinikum Rostock	Rostock
Germany	Universitätsklinikum Ulm	Ulm
Germany	Internistische Praxis Weyhe	Weyhe
Hungary	Clinexpert Egészségügyi Szolgáltató És Kereskedelmi Kft.	Budapest
Hungary	Pannónia Magánorvosi Centrum Kft	Budapest
Hungary	Semmelweis Egyetem Altalanos Orvostudomanyi Kar	Budapest
Hungary	Semmelweis Egyetem Altalanos Orvostudomanyi Kar Sebeszeti, Transzplantacios es Gasztroenterologiai Klinika	Budapest
Hungary	SzTE Szt-Gy A Orvostud Kar Bel Klin	Szeged
Israel	The Barzilai Medical Center	Ashkelon
Israel	The Edith Wolfson Medical Center	H_olon
Israel	Hadassah Medical Organization, Hadassah Medical Center, Ein-	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Galilee Medical Center (Western Galilee Hospital)	Nahariya
Israel	Kaplan Medical Center	Rehovot
Italy	ASST Papa Giovanni XXIII - Cardiologia - Bergamo	Bergamo
Italy	AO Brotzu	Cagliari
Italy	Universita degli Studi di Firenze - Azienda Ospedaliero - Un	Firenze
Italy	IRCCS Ospedale San Raffaele	Milan
Italy	Azienda Ospedaliera San Gerardo	Monza
Italy	AOU di Padova	Padova
Italy	Policlinico Universitario Campus Biomedico	Rom
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata (P	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	A.O. Ordine Mauriziano Di Torino	Torino
Italy	AOU S. Maria della Misericordia	Udine
Italy	Universita degli Studi dell'Insubria - Ospedale di Circolo e	Varese
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Hanyang University Guri Hospital	Guri-Si
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Seoul National University Bundang Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital	Soeul
Korea, Republic of	Kyung Hee University Hospital - Internal Medicine	Soeul
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon-Si
Korea, Republic of	Yonsei University, Wonju Severance Christian Hospital	Wonju
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno Klinikos	Kaunas
Lithuania	Klaipeda Seamen's Hospital	Klaipeda
Lithuania	Republic Klaipeda Hospital	Klaipeda
Lithuania	Panevezio ligonine	Panevezys
Lithuania	Vilniaus Universiteto ligonines Santariskiu Klinikos	Vilnius
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango
Mexico	Medical Care and Research S. A. de C. V	Merida
Mexico	Clinicos Asociados Bocm, S.C.	Mexico City
Mexico	Centro Regiomontano de Estudios Clinicos Roma SC	Monterrey
Mexico	Clinical Research Institute S.C.	Tlalnepantla
Netherlands	Radboud University Medical Center	Nijmegen
Norway	Ålesund Hospital, Møre & Romsdal Hospital trust, Dept. of Medicine, div of Gastroenterology and the Clinical research unit HMR	Ålesund
Norway	Akershus Universitetssykehus	Lørenskog
Norway	Vestfold Hjertesenter As	Tønsberg
Norway	Universitetssykehuset Nord-Norge Tromsø, Gastrolab, Medisinsk poliklinikk, B8	Tromsø
Poland	MPS - MED sp. z o.o.	Grudziadz
Poland	MZ Badania Slowik Zymla Spolka jawna	Knurow
Poland	Centrum Medyczne PROMED	Krakow
Poland	Krakowskie Centrum Medyczne Sp. z o.o.	Krakow
Poland	Centrum Medyczne Plejady	Kraków
Poland	Szpital Zakonu Bonifratrow Sw. Jana Bozego w Lodzi	Lodz
Poland	Klinika Badawcza Centrum Badawcze Panaceum Agnieszka Brzezicka, Magdalena Lenkiewicz Sp. z o.o.	Malbork
Poland	Twoja Przychodnia - Opolskie Centrum Medyczne	Opole
Poland	Medicome Sp. z o.o.	Oswiecim
Poland	Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu	Poznan
Poland	ETG Skierniewice	Skierniewice
Poland	KO-MED Centra Kliniczne Staszow	Staszow
Poland	Twoja Przychodnia - SCM	Szczecin
Poland	GASTROMED Kopon, Zmudzinski i Wspólnicy spólka jawna, Specjalistyczne Centrum Gastrologii i Endoskopii, Specjalistyczne Gabinety Lekarskie	Torun
Poland	Centrum Zdrowia Matki, Dziecka i Mlodziezy	Warsaw
Poland	Bodyclinic sp. z o.o. sp.k.	Warszawa
Poland	Centralny Szpital Kliniczny MSWiA w Warszawie	Warszawa
Poland	PlanetMed	Wroclaw
Poland	ETG Zamosc	Zamosc
Portugal	Hospital Prof. Doutor Fernando Fonseca (HFF) (Hospital Amadora Sintra)	Amadora
Portugal	Hospital de Braga	Braga
Portugal	Hospital Beatriz Angelo (HBA)	Loures
Portugal	Centro Hospitalar de Entre o Douro e Vouga (CHEDV)- Hospital São Sebastião	Santa Maria da Feira
Romania	Spitalul Clinic Colentina	Bucharest
Romania	Sana Monitoring	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta Cluj-Napoca	Cluj-Napoca
Romania	Spitalul Clinic Judetean de Urgenta "Sf. Spiridon" Iasi	Iasi
Romania	Spitalul Clinic Judetean Mures	Târgu Mure?
Romania	Cabinet Particular Policlinic Algomed	Timisoara
Serbia	Zvezdara University Medical Center	Belgrad
Serbia	Clinic Center of Serbia	Belgrade
Serbia	Clinical Hospital Center "Dr. Dragisa Misovic"	Belgrade
Serbia	Euromedik Hospital	Belgrade
Serbia	Clinical Center Kragujevac - Center for Gastroenterohepatology	Kragujevac
Serbia	General Hospital Dr Djordje Joanovic	Zrenjanin
Serbia	General hospital Zrenjanin	Zrenjanin
Slovakia	FNsP F.D.R. Banska Bystrica	Banska Bystrica
Slovakia	CLINIQ s.r.o.	Bratislava
Slovakia	ENDOMED s.r.o.	Košice
Slovakia	GASTROMEDIC, s.r.o.	Nove Zamky
Slovakia	Accout Center s.r.o.	Sahy
Sweden	Örebro Univ. Hospital	Örebro
Sweden	Karolinska Universitetssjukhuset - Gastroenterology	Stockholm
Sweden	Uppsala University Hospital, Akademiska	Uppsala
Turkey	Hacettepe University Medical Faculty - Hematology	Ankara
Turkey	Istanbul University Medical Faculty	Istanbul
Turkey	Mersin Universtiy Medical Faculty	Mersin
United Kingdom	Northern Care Alliance NHS Foundation Trust-Fairfield General Hospital - Gastroenterology	Bury
United Kingdom	Accellacare Warwickshire Quality Research Site	Coventry
United Kingdom	County Durham and Darlington NHS Foundation Trust (CDDFT) - Darlington Memorial Hospital	Darlington
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	North West London Hospitals NHS Trust	Harrow
United Kingdom	Central Middlesex Hospital	London
United Kingdom	Kings College Hospital	London
United Kingdom	Accellacare North London	Northwood
United Kingdom	Accellacare Limited/Accellacare of South London	Orpington
United Kingdom	Royal Berkshire Hospital	Reading
United States	Dayton Gastroenterology	Beavercreek	Ohio
United States	RecioMed Clinical Research Network, Inc.	Boynton Beach	Florida
United States	Digestive Health Associates of Texas, PA	Carrollton	Texas
United States	Carolina Digestive Health Associates, PA	Charlotte	North Carolina
United States	MB & V Medical Research	Doral	Florida
United States	Gastroenterology Associates of Northern Virginia	Fairfax	Virginia
United States	Amicis Research Center	Granada Hills	California
United States	Carolina Research	Greenville	North Carolina
United States	Peters Medical Research	High Point	North Carolina
United States	Baylor College of Medicine - Gastroeneterology	Houston	Texas
United States	Clinical Research Solution: Digestive Health Associates	Houston	Texas
United States	A+ Research, Inc.	Miami	Florida
United States	D&H National Research Centers, Inc.	Miami	Florida
United States	I.V.A.M. Clinical & Investigational Center LLC	Miami	Florida
United States	Medical Professionals Clinical Research Center	Miami	Florida
United States	SouthCoast Research Center, Inc	Miami	Florida
United States	Wisconsin Center For Advanced Research	Milwaukee	Wisconsin
United States	Allameh Medical Corporation	Mission Viejo	California
United States	Gastroenterology Group Of Naples	Naples	Florida
United States	Lenox Hill Hospital	New York	New York
United States	Prospective Research Innovations Inc.	Rancho Cucamonga	California
United States	Alliance Clinical Research - Gastroenterology	Tampa	Florida
United States	Valiance Clinical Research	Tarzana	California
United States	Cotton O'Neil Clinical Research Center	Topeka	Kansas
United States	Clinical Research Institute of Michigan	Troy	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
InDex Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bosnia and Herzegovina,  Brazil,  Canada,  Croatia,  Denmark,  France,  Georgia,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Lithuania,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Romania,  Serbia,  Slovakia,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Induction - Proportion of participants with clinical remission.	Clinical remission defined by the 3-component Mayo score.	Week 6
Primary	Maintenance - Proportion of participants with clinical remission.	Clinical remission defined by the 3-component Mayo score.	Week 52
Secondary	Induction - Proportion of participants with endoscopic improvement.	Endoscopic improvement defined by the Mayo Endoscopic score.	Week 6
Secondary	Induction - Proportion of participants with symptomatic remission.	Symptomatic remission defined by the 2-component Mayo score.	Week 6
Secondary	Induction - Proportion of participants with clinical response.	Clinical remission defined by the 3-component Mayo score.	Week 6
Secondary	Induction - Proportion of participants with normalisation of stool frequency.	Stool frequency defined by the Mayo score for Stool Frequency.	Week 6
Secondary	Induction - Proportion of participants with absence of rectal bleeding.	Rectal bleeding defined by the Mayo score for Rectal Bleeding.	Week 6
Secondary	Induction - Mean stool frequency.	Mean stool frequency defined by the Mayo score for Stool Frequency.	Week 6
Secondary	Induction - Proportion of participants with histologic improvement.	Defined by the Robarts Histologic Index.	Week 6
Secondary	Induction - Proportion of participants with histologic remission.	Histologic remission defined by the Robarts Histologic Index.	Week 6
Secondary	Induction - Proportion of participants with mucosal healing.	Mucosal healing defined by the Mayo Endoscopic score and Robarts Histologic Index.	Week 6
Secondary	Induction - Mean ln-transformed faecal calprotectin.	Mean ln-transformed faecal calprotectin defined by faecal calprotectin values.	Week 6
Secondary	Induction - Mean 3-component and 4-component Mayo scores.	Defined by 3-component and 4-component Mayo scores.	Week 6
Secondary	Induction - Mean IBDQ total score.	Defined by the Inflammatory Bowel Disease Questionnaire (IBDQ).	Week 6
Secondary	Induction - Proportion of participants with an improvement in IBDQ total score.	Defined by the IBDQ.	Week 6
Secondary	Maintenance - Proportion of participants with endoscopic improvement.	Endoscopic improvement defined by the Mayo Endoscopic score.	Week 52
Secondary	Maintenance - Proportion of participants with clinical remission and steroid-free.	Defined by the 3-component Mayo score and use of glucocorticosteroids.	Week 52
Secondary	Maintenance - Proportion of participants with clinical remission among those who achieved clinical remission	Defined by the 3-component Mayo score.	Week 52
Secondary	Maintenance - Proportion of participants with symptomatic remission.	Symptomatic remission defined by the 2-component Mayo score.	Week 52
Secondary	Maintenance - Proportion of participants with histologic improvement.	Histologic improvement defined by the Robarts Histologic Index.	Week 52
Secondary	Maintenance - Proportion of participants with histologic remission.	Histologic remission defined by the Robarts Histologic Index.	Week 52
Secondary	Maintenance - Proportion of participants with mucosal healing.	Mucosal healing defined by the Mayo Endoscopic score and Robarts Histologic Index.	Week 52
Secondary	Maintenance - Proportion of participants with clinical response.	Clinical response defined by the 3-component Mayo score.	Week 52
Secondary	Maintenance - Proportion of participants with absence of rectal bleeding.	Rectal bleeding defined by the Mayo score for Rectal Bleeding.	Week 52
Secondary	Maintenance - Proportion of participants with normalisation of stool frequency.	Stool frequency defined by the Mayo score for Stool Frequency.	Week 52
Secondary	Maintenance - Mean stool frequency.	Mean stool frequency defined by the Mayo score for Stool Frequency.	Week 52
Secondary	Maintenance - Mean ln-transformed faecal calprotectin.	Mean ln-transformed faecal calprotectin.	Week 52
Secondary	Maintenance - Mean 3-component and 4-component Mayo scores.	Defined by 3-component and 4-component Mayo scores.	Week 52
Secondary	Maintenance - Mean IBDQ total score.	Defined by the use of the Inflammatory Bowel Disease Questionnaire (IBDQ).	Week 52
Secondary	Maintenance - Proportion of participants with an improvement in IBDQ total score.	Defined by the IBDQ.	Week 52