Clinical trial NCT02327221: Study Evaluating Ovasave, an Autologous Cell Therapy, in Patients With Active Crohn's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn Disease
Keywords: Crohn Disease
Cell therapy
Regulatory T lymphocytes
Treg
Autologous
Antigen specific T regulatory lymphocytes
Lead sponsor: TxCell
Sponsor class: INDUSTRY
First posted: 2014-12-30
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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;

Primary outcomes:
measure: CDAI response
timeFrame: 6 weeks post administration
Secondary outcomes:
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Liege
country: Belgium
facility: CHU Liege
city: Amiens
country: France
facility: CHU d'Amiens Sud
city: Besançon
country: France
facility: CHU de Besançon, Hôpital Jean Minjoz
city: Clichy
country: France
facility: Hôpital Beaujon
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Lille
country: France
facility: CHRU de Lille, Hôpital Claude Huriez
city: Nancy
country: France
facility: CHU de Nancy, Hôpital de Brabois Adulte
city: Nice
country: France
facility: CHU de Nice, Hôpital de l'Archet 2
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital St-Antoine
city: Pessac
country: France
facility: CHU de Bordeaux, Hôpital Haut-Lévêque
city: Toulouse
country: France
facility: CHU de Toulouse, Hôpital Rangueil
city: Berlin
country: Germany
facility: Krankenhaus Waldfriede e.V.
city: Frankfurt am Main
country: Germany
facility: Markus Hospital
city: Hannover
country: Germany
facility: Hannover Medical School
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein
city: Minden
country: Germany
facility: Gastroenterologische Gemeinschaftpraxis
city: Ulm
country: Germany
facility: Universitätsklinik Ulm
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Milano
country: Italy
facility: Istituto Clinico Humanitas
city: Roma
country: Italy
facility: Complesso Integrato Columbus
city: Roma
country: Italy
facility: Ospedale San Camillo-Forlanini
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: UZ Gasthuisberg, Gent (Belgium)
name: Severine VERMEIRE, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.