Phase II study evaluating Ovasave, a cell therapy, in patient with active Crohn's Disease

Phase 1

• Conditions: Moderately to severely active Crohn's Disease; MedDRA version: 19.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2014-001295-65-BE
• Lead Sponsor: TxCell

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-11-17
• Last Update Posted: 31 October 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 117

Inclusion Criteria

Patients meeting the following criteria:

1) Willing and able to provide written Informed Consent (IC);
2) Male or Female aged between 18 and 70 (inclusive) years of age;
3) Crohn's Disease diagnosis defined as patients with medical history of signs, symptoms and biological evidence of active bowel inflammation:
- Documented Magnetic Resonance Imaging (MRI) or endoscopic evidence of inflammatory bowel disease (IBD), compatible with Crohn's diagnosis at least 1 year prior to V1;
AND
- Available endoscopy or MRI, performed within 1 year prior to V1. If the one available has more than 1 year at V1, a new exam (endoscopy or MRI) needs to be performed prior to V2;
4) Documented CDAI (Crohn's Disease Activity Index) = 250 at V1 or within 12 weeks prior to V1;
5) Elevated High sensitive C-reactive protein (hs-CRP) > 10 mg/L at V1;
6) Calprotectin = 250 µg/g at V1;
7) Failure (primary or secondary) or intolerance to conventional treatments including corticosteroid, immunosuppressant and at least one biologics at a dose indicated for CD (Refer to Appendix 17.6 for the definition of refractoriness);
8) Total white cell count between 4.0.10e9 /L and 15.10e9 /L (included);
9) Platelets between 150.10e9 and 600.10e9 /L (included);
10) Hemoglobin between 8.5 g/dL and 16 g/dL (included);
11) Full Blood Count (FBC) and biochemistry without any clinically significant abnormality except if CD-related, at Investigator's discretion;
12) Prothrombin Time (PT) between 70% and 100% (or International Normalized Ratio (INR) between 0.8 and 1.2) and activated Partial Thromboplastin Time (aPTT) between 0.8 and 1.2 (Ratio);
13) Normal electrocardiogram (ECG) or without any clinically significant abnormality at Investigator's discretion;
14) Patients willing and able to observe an intake of ovalbumin through the daily ingestion of a meringue (cooked pasteurized egg white with sugar) after the first IMP administration until the end of the Double- Blind phase and during the Open-Label phase.

Additional eligibility criteria for IMP administration:

At the Visit 3 (Week -4):

1) CDAI = 250;
2) Evidence of inflammation by an elevated hs-CRP value (> 5 mg/L);
OR elevated calprotectin (= 250 µg/g);
OR endoscopic / MRI evidence of local intestinal inflammation (to be confirmed before V4);
3) Absence of any of the following conditions:
- Concomitant abdominal, perianal or anal undrained abscess;
- Actively draining fistula;
- Anal or rectal stricture/stenosis;
- Clinically active infection (the study visit should be postponed until the infection is resolved).

At Visit 4 (Week 0): Absence of any of the following conditions:

- Concomitant abdominal, perianal or anal undrained abscess;
- Actively draining fistula;
- Clinically active infection (the study visit should be postponed until the infection is resolved).

At each subsequent administration visits (V7, V10, V12): Absence of clinically active infection (the study visit should be postponed until the infection is resolved).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 108
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion Criteria

Patients presenting with any of the following will not be included in the study:

1) Current or recent history (within 1 year prior to V1) of major organ or system failure or condition, acute or chronic that in the opinion of the Investigator should preclude enrolment, except Crohn's Disease;
2) Current or previous history of malignancy except a local basal cell carcinoma without metastases;
3) History of major immune deficiency disorder, except Crohn's Disease;
4) Gamma immunoglobulinaemia < 6 g/L at V1;
5) First degree family or personal history of clinically significant venous or arterial thromboembolism events;
6) History of thrombocytosis over 600.10e9 / L within 1 year prior to V1;
7) History of tuberculosis (TB) except if documentation of adequate compliance to treatment is provided. Test to be performed at V1 if not already done within 12 weeks prior to V1;
8) Concomitant clinically active infection;
9) Serious infection (as per definition of severe sepsis) within 12 weeks prior to V1;
10) Opportunistic infections within 6 months (26 weeks) prior to V1;
11) Infectious enteritis within 4 weeks prior to V1;
12) Evidence of Clostridium difficile at V1;
13) History of Human Immunodeficiency Virus (HIV);
14) Recent history of contamination by the Epstein-Barr virus (EBV), Cytomegalovirus (CMV) and/or toxoplasma within 6 months (26 weeks) prior to V1. If EBV or CMV positive at V1, virus load will be performed at V2. If positive at V2, virus load will be assessed again at V3. If decrease, and upon discussion with the medical monitor, the patient could
continue the study;
15) Inflammatory eye disease;
16) Pyoderma gangrenosum;
17) History of intestinal resection or intra-abdominal surgery within 6 months (26 weeks) prior to V1 or any previous major gastrointestinal (GI) resection;
18) Patients with ileostomy or colostomy;
19) Patients with short bowel syndrome with less than 1.5 m of small bowel;
20) Complication of Crohn's Disease such as strictures/stenosis, penetrating disease, or any other manifestation that might require surgery, could preclude the use of CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with Ovasave;
21) Intestinal functional fibrotic stricture/stenosis responsible for the patient's symptoms;
22) Parenteral nutrition if not compatible with the meringue intake;
23) Documented history of hypersensitivity or intolerance to chicken eggs;
24) History of known hypersensitivity or intolerance to any component of the IMP (refer to Appendix 17.7 for the composition of the IMP);
25) Females of childbearing potential who are either pregnant, breastfeeding or not using any birth control method. Female patients of childbearing potential must have a negative pregnancy test at Screening and must agree to use an acceptable method of birth control with a low failure rate (i.e. less than 1% per year) in a consistent and correct manner for the whole duration of the study treatment period and during 20 weeks following the last IMP administration. Abstinence, oral birth control pills administered for at least 2 monthly cycles prior to IMP administration, a contraceptive vaginal ring (e.g. NuvaRing or equivalent) or a contraceptive transdermal patch (e.g. EVRA or equivalent) administered for at least 2 monthly cycles prior to IMP administration, an IUD, or medroxyprogesterone acetate administered intramuscularly or a subcutaneous implant of etonogestrel (e.g.
Implanon or equivalent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Confirmation of the ability of a single intravenous (i.v.) administration of Ovasave at 1.10e6 cells (Ova-Treg cells) to induce a CDAI response (CDAI decrease = 100 points) 6 weeks post administration compared to placebo.;Secondary Objective: - Safety assessment of a single and multiple i.v. administrations of Ovasave.<br>- Assessment of the efficacy of the dose 1.10e6 cells compared to placebo on CDAI, steroid sparing effect, inflammatory markers and Investigator's and patient's opinion on the IMP.<br>- Assessment of safety during the 3-year Long-Term Safety Follow-Up after first administration.;Primary end point(s): The primary clinical efficacy endpoint is the percentage of patients with a CDAI response in the active group of Ovasave at 1.10e6 cells, 6 weeks after 1 administration (V6=Week 6) compared to placebo.;Timepoint(s) of evaluation of this end point: 6 weeks after 1 Ovasave administration (Visit 6)