Study Evaluating Ovasave, an Autologous Cell Therapy, in Patients With Active Crohn's Disease (CATS29)

A Phase IIb, Multicentre, Randomised, Double-blinded, Placebo-controlled, Multi-dose and Multi-injection, Parallel Groups Study to Evaluate the Efficacy and the Safety of Ovasave in Patients With Active Refractory Crohn's Disease

The investigational product, named Ovasave (Ova-Treg), is a cell-based therapy, consisting of an autologous antigen-specific regulatory type 1 T lymphocyte expanded population administered via the intravenous route as an infusion.

The study is a multicenter, randomised, double-blinded, placebo-controlled, multi-dose and multi-injection study; followed with a 16-week phase with either the possibility for an open-label treatment part or a safety follow-up part with no injection.

Then, the patients will be followed in an additional long-term safety follow-up, of maximum duration of 3 years from the first administration.

Study Overview

• Status: Terminated
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Ovasave; Drug: Placebo

Detailed Description

During double-blinded phase, the treatment consists of 2 intravenous (i.v.) administrations of antigen-specific autologous T regulatory cells or placebo:

• Group A: 1.10e4 cells and 1.10e4 cells
• Group B: 1.10e6 cells and 1.10e6 cells
• Group C: 1.10e7 cells and 1.10e7 cells
• Group D: Placebo and Placebo

During double-blinded phase, two i.v. administrations of study drug (Ova-Treg) will be administered, one at week 0 and another one at week 8 for the group A, B and C. Two injections of Placebo will be administered, one at week 0 (V4) and another one at week 8 for the group D. During double-blinded phase, all the patients will be followed during 16 weeks. This will be followed by an additional period of 16 weeks when the patient is expected to receive two additional administrations of Ovasave at 10e6 cells dose (Open-label phase), except if refused by the patient or not recommended by the Investigator, representing the follow-up phase. These third and fourth administrations will be performed for all groups (A, B, C and D) with an injection of Ovasave at 1.10e6 cells administered at week 16 and week 24. A patient who didn't receive the 2 first administrations during the double-blinded phase cannot receive the third and the fourth administration during Open-label phase.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Medical University Innsbruck
  • Vienna, Austria
    • Medical University of Vienna
• Belgium
  • Bruxelles, Belgium
    • Cliniques Universitaires Saint-Luc
  • Gent, Belgium
    • UZ Gent
  • Leuven, Belgium
    • UZ Gasthuisberg
  • Liege, Belgium
    • CHU Liege
• France
  • Amiens, France
    • CHU d'Amiens Sud
  • Besançon, France
    • CHU de Besancon, Hopital Jean Minjoz
  • Clichy, France
    • Hopital Beaujon
  • Créteil, France
    • Hôpital Henri Mondor
  • Lille, France
    • CHRU de Lille, Hopital Claude Huriez
  • Nancy, France
    • CHU de Nancy, Hôpital de Brabois Adulte
  • Nice, France
    • CHU de Nice, Hôpital de l'Archet 2
  • Paris, France
    • Hôpital Saint-Louis
  • Paris, France
    • Hôpital St-Antoine
  • Pessac, France
    • CHU de Bordeaux, Hôpital Haut-Lévêque
  • Toulouse, France
    • CHU de Toulouse, Hôpital Rangueil
• Germany
  • Berlin, Germany
    • Krankenhaus Waldfriede e.V.
  • Frankfurt am Main, Germany
    • Markus Hospital
  • Hannover, Germany
    • Hannover Medical School
  • Kiel, Germany
    • University Hospital Schleswig-Holstein
  • Minden, Germany
    • Gastroenterologische Gemeinschaftpraxis
  • Ulm, Germany
    • Universitätsklinik Ulm
• Italy
  • Firenze, Italy
    • Azienda Ospedaliero-Universitaria Careggi
  • Milano, Italy
    • Istituto Clinico Humanitas
  • Roma, Italy
    • Complesso Integrato Columbus
  • Roma, Italy
    • Ospedale San Camillo-Forlanini
• United Kingdom
  • London, United Kingdom
    • Guy'S and St Thomas' Nhs Foundation Trust
  • Southampton, United Kingdom
    • Southampton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Active Crohn's Disease diagnosis defined as patients with medical history of signs, symptoms and biological evidence of active bowel inflammation:

   • Documented endoscopic evidence of inflammatory bowel disease (IBD), compatible with Crohn's diagnosis at least 1 year prior to screening and
   • High sensitive C-reactive protein (hs-CRP) > 10 mg/L at V1.
2. Failure or intolerance to conventional treatments including corticosteroid, immunosuppressant and at least one biologics; and had not responded (primarily failure) or responded and then lost response completely (no response or need to increase the dose / secondary failure) or were intolerant to this therapy at a dose indicated for CD
3. Documented CDAI (Crohn's Disease Activity Index) above 250 points (CDAI ≥ 250) at screening or within the past 3 months;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; During CATS29-Double blind phase, two intravenous administrations of study drug will be administered, one at week 0 and another one at week 8.
Active Comparator: Ovasave - Dose 10e4	Drug: Ovasave; During CATS29-Double blind phase, two intravenous administrations of study drug will be administered, one at week 0 and another one at week 8.
Active Comparator: Ovasave - Dose 10e6	Drug: Ovasave; During CATS29-Double blind phase, two intravenous administrations of study drug will be administered, one at week 0 and another one at week 8.
Active Comparator: Ovasave - Dose 10e7	Drug: Ovasave; During CATS29-Double blind phase, two intravenous administrations of study drug will be administered, one at week 0 and another one at week 8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CDAI response	Controlled versus placebo confirmation of the ability of a single intravenous (i.v.) injection of 1.10e6 cells dose of Ovasave (Ova-Treg cells) to induce a CDAI response (CDAI decrease ≥ 100 points)	6 weeks post administration

Collaborators and Investigators

• Sponsor: TxCell
• Investigators: Principal Investigator: Severine VERMEIRE, MD, UZ Gasthuisberg, Gent (Belgium)

Publications and helpful links

General Publications

• Desreumaux P, Foussat A, Allez M, Beaugerie L, Hebuterne X, Bouhnik Y, Nachury M, Brun V, Bastian H, Belmonte N, Ticchioni M, Duchange A, Morel-Mandrino P, Neveu V, Clerget-Chossat N, Forte M, Colombel JF. Safety and efficacy of antigen-specific regulatory T-cell therapy for patients with refractory Crohn's disease. Gastroenterology. 2012 Nov;143(5):1207-1217.e2. doi: 10.1053/j.gastro.2012.07.116. Epub 2012 Aug 8.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: December 23, 2014
• First Submitted That Met QC Criteria: December 29, 2014
• First Posted (Estimate): December 30, 2014

Study Record Updates

• Last Update Posted (Actual): April 25, 2017
• Last Update Submitted That Met QC Criteria: April 24, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Autologous; Cell therapy; Crohn Disease; Treg; Regulatory T lymphocytes; Antigen specific T regulatory lymphocytes
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: TXC-CD-002-2011; 2014-001295-65 (EudraCT Number)