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

• Register: EUCTR
• Last refreshed on: 14 November 2016
• Main ID: EUCTR2014-001295-65-AT
• Date of registration: 19/11/2014
• Prospective Registration: Yes
• Primary sponsor: TxCell
• Public title: Phase II study evaluating Ovasave, a cell therapy, in patient with active Crohn's Disease
• Scientific title: A phase IIb, multicentre, randomised, double-blinded (DB), placebo-controlled, single-dose and multi-injection, parallel groups study to evaluate the efficacy and the safety of Ovasave (ovalbumin-specific autologous Treg cells (ova-Treg)) in patients with active refractory Crohn’s Disease (Crohn’s And Treg Study: CATS29) - CATS29
• Date of first enrolment: 01/12/2014
• Target sample size: 170
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001295-65
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Germany, Italy

Contacts

• Name: Clinical Department
• Affiliation: TxCell

• Name: Clinical Department
• Affiliation: TxCell

Key inclusion & exclusion criteria

Inclusion criteria:
Patients with active refractory Crohn's Disease, 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 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 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 (Refer to Appendix 17.6 for the definition of refractoriness);
8) Total white cell count between 4.0.10e9 /L and 10.10e6 /L;
9) Platelets between 150.10e9 and 600.10e9 /L (included);
10) Hemoglobin between 8.5 g/dL and 16 g/dL;
11) Full Blood Count (FBC) and biochemistry without any clinically significant abnormalities except if CD-related, at Investigator's discretion;
12) Prothrombin Time (PT) between 70-100% (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, or no clinically significant abnormality in the electrocardiogram (ECG) at Investigator's discretion;
14) Patients willing and able to observe an intake of ovalbumin through the ingestion of a meringue (cooked pasteurized egg white with sugar) daily after the first administration until the end of the DB-phase and during the OL-phase if the patient receives additional administration.

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;
- Clinically active infection.

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

- Concomitant abdominal, perianal or anal undrained abscess;
- Presence of actively draining fistula;
- Clinically active infection.

At each subsequent administration visits (V7, V9, V11): Absence of clinically active infection.
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 157
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

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 or any signs or history of major immune deficiency disorder;
5) First degree family or personal history of clinically significant venous, arterial or pulmonary 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 in the 12 weeks prior to V1;
8) Concomitant clinically active infection;
9) Serious infection (as per definition of 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 or 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 or pyoderma gangrenosum;
16) History of intestinal resection or intra-abdominal surgery within 6 months (26 weeks) prior to V1;
17) Patients with ileostomy or colostomy;
18) Patients with short bowel syndrome with less than 1.5 m of small bowel;
19) Complication of Crohn's Disease such as strictures, stenosis, short gut syndrome, 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;
20) Intestinal functional fibrotic stricture responsible for the patient's symptoms or previous major gastrointestinal (GI) resection;
21) Parenteral nutrition if not compatible with the meringue intake;
22) History of documented hypersensitivity or intolerance to chicken eggs;
23) History of known hypersensitivity or intolerance to any component of the IMP (Refer to Appendix 17.7 for the composition of the IMP);
24) Females of childbearing potential who are either pregnant, breastfeeding or without the use of birth control. 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 12 weeks 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,

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderately to severely active Crohn's Disease
MedDRA version: 18.1 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: Ovasave
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Ova-Treg
CAS Number: -
Current Sponsor code: Ova-Treg
Other descriptive name: Autologous ovalbumin-specific type 1 regulatory T lymphocytes expanded population
Concentration unit: Other
Concentration type: equal
Concentration number: 10e6-
Pharmaceutical form of the placebo: Suspension for injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): The primary clinical efficacy endpoint is the percentage of patients with a CDAI response (CDAI decrease from baseline = 100 points) in the active group of 10^6 Ova-Treg cells, 6 weeks after 1 Ovasave administration (Week 6= V6) compared to placebo.

Timepoint(s) of evaluation of this end point: 6 Weeks after 1 Ovasave administration (Visit 6)

Main Objective: Controlled versus placebo confirmation of the ability of a single intravenous (i.v.) injection of 1.10^6 cells dose of Ovasave (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 first and second i.v. injection of Ovasave (CATS29-DB) and of a 3rd and 4th i.v. injection of Ovasave (CATS29-OL).
- Assessment of the efficacy and the safety of the dose 1.10e6 cells compared to Placebo.
- Assessment at V8 (Week 14) of the safety and efficacy (response and remission) of a second injection of 1.10e6 cells (performed at V7 (Week 8)).
- Reduction of steroids treatment at V8 (Week 14).
- Assessment of safety during the 3-year Long-Term Safety Follow-Up after first dose.

Secondary Outcome(s)

Secondary end point(s): - CDAI:

• Percentage of patients with a CDAI remission (CDAI < 150 points) and response (CDAI decrease from baseline = 100 points) 6 weeks after the second administration (V8=Week 14),
• Percentage of patients with a CDAI response at each other postbaseline visit,
• Percentage of patients achieving a CDAI remission (CDAI < 150 points) at each post-baseline visit,
• Raw value in CDAI total score at each post-baseline visit,
• Raw value in each CDAI sub-score at each post-baseline visit,
• Change from baseline in CDAI total score at each post-baseline visit.

- Steroids sparing effect:

• Steroid decrease from Visit 7 (Week 8) will be recorded at Visit 8 (Week 14) (including the daily dose taken between V7 and V8),
• Percentage of patient by decrease steroids dose (decrease in total of 20, 15, 10, 5 or 0 mg/day) at Week 14.

- Inflammatory markers:

• Raw value in hs-CRP at each post-baseline visit,
• Change from baseline in hs-CRP at each post-baseline visit,
• Raw value in Calprotectin at each post-baseline visit,
• Change from baseline in Calprotectin at each post-baseline visit.

- Investigator's opinion on the investigational product:

• Qualify the investigational product,
• Would you like to test the investigational product again?

Timepoint(s) of evaluation of this end point: - CDAI:

• At Visit 8 (Week 14)
• At each other post-baseline visit
• At each post-baseline visit
• At each post-baseline visit
• At each post-baseline visit
• At each post-baseline visit

- Steroids sparing effect:

• At Visit 8 (Week 14)
• At Visit 8 (Week 14)

- Inflammatory markers:

• At each post-baseline visit
• At each post-baseline visit
• At each post-baseline visit
• At each post-baseline visit

- Investigator's opinion on the investigational product:

• At Visit 9 (Week 16) and Visit 13 (Week 32), and at Early Termination Visit (ET)
• At Visit 9 (Week 16) and Visit 13 (Week 32), and at Early Termination Visit (ET)

Secondary ID(s)

2014-001295-65-BE

NCT02327221

TXC-CD-002-2011

Source(s) of Monetary Support

TxCell