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: 17.1Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-11-27
• Last Update Posted: 14 November 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

At the screening visit (V1):

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 endoscopic evidence of Crohn's diagnosis at least 1 year prior to V1 (an endoscopy will be perform if the one available has more than 1 year at V1);
4) Elevated High sensitive C-reactive protein (hs-CRP) > 10 mg/L at V1;
5) Calprotectin = 250 µg/g;
6) Failure or intolerance to conventional treatments including corticosteroid, immunosuppressant and at least one biologic; 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 (Refer to Appendix 17.6 for the definition of refractoriness);
7) Documented CDAI (Crohn's Disease Activity Index) = 250 at V1 or within the past 3 months prior to V1;
8) Total white cell count = 4.0.10^9 / L;
9) Platelets between 150.10^9 and 600.10^9 / L (included);
10) Hemoglobin > 8.5 g/dL;
11) Full blood count (FBC) and biochemistry without any clinically significant abnormalities except if CD-related, at Investigator's discretion;
12) Normal, or no clinically significant abnormality in the electrocardiogram (ECG) at Investigator's discretion;
13) Patients willing and able to observe an intake of ovalbumin through the ingestion of a meringue daily after the first administration until the end of the Double-blind phase and during the OL-phase if the patient receives additional administration;

At the Visit 3 (week-4):

1) CDAI = 250;
2) Evidence of inflammation by an elevated hs-CRP value (> 5 mg/L) OR endoscopic / MRI evidence of local intestinal inflammation, OR elevated calprotectin (= 250µg/g) to be confirmed before V4 (first administration);

Between visit 8 (week14) and visit 9 (week16):

1) Upon Investigator recommendation, patient qualification will be based on acceptable safety and tolerability profile of the IMP before continuing to receive intravenous administrations of Ovasave at a dose of 10^6 cells.
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 185
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1) Current or recent history (12 preceding months before 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) First degree family or personal history of clinically significant venous, arterial or pulmonary thromboembolism events;
4) History of thrombocytosis over 600.10^9 / L in the previous 12 months prior to V1;
5) History of major immune deficiency disorder, except Crohn’s Disease;
6) Concomitant clinically active infection at V1 or V2 or V3 or V4 or V7 or V9 CATS29-OL or V11 CATS29-OL;
7) History of intestinal resection or intra-abdominal surgery within 6 months prior to V1;
8) Have complication of Crohn’s Disease such as strictures, stenosis, short gut syndrome, 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;
9) Patients with intestinal functional fibrotic structuring responsible for the patient’s symptoms or previous major Gastro Intestinal (GI) resection;
10) Patients with short bowel syndrome or with less than 1.5 m of small bowel;
11) Presence of actively draining fistula at V3 or V4;
12) Concomitant abdominal or anal undrained abscess at V3 or V4;
13) History of documented hypersensitivity or intolerance to chicken eggs;
14) Parenteral nutrition if not compatible with the meringue intake;
15) History of known hypersensitivity or intolerance to any component of the IMP (Refer to Appendix 17.7 of the Protocol for the composition of the Drug Product);
16) Patients with ileostomia or colostomy;
17) History of tuberculosis (TB) except if documentation of adequate compliance to treatment is provided,
18) Gamma immunoglobulinaemia < 6 g/L at Screening visit (V1) or Pre-entry visit (V3) or any signs or history of major immune deficiency disorder;
19) Recent history of contamination by the Epstein-Barr virus (EBV), Cytomegalovirus (CMV) and/or toxoplasma within 6 months prior to V1;
20) History of human immunodeficiency virus (HIV);
21) Females of childbearing potential who are either pregnant, breast-feeding or without the use of birth control. Female patients of child-bearing 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 the 3 months following the end of the study treatment period (V13/week 32). Abstinence, oral birth control pills administered for at least 2 monthly cycles prior to study drug 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 study drug administration, an IUD, or medroxyprogesterone acetate administered intramuscularly or a subcutaneous implant of etonogestrel (Implanon or equivalent) for a minimum of one month prior to study drug administration are acceptable methods of birth control for inclusion into the study. Female subjects are considered of childbearing potential unless they are postmenopausal (absence of menstrual bleeding for 1 year - or 6 months if laboratory confirmation o

Study & Design

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