A phase II, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety and immunogenicity of Neovacs’TNFa-Kinoid in adult subjects with Crohn’s Disease

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2010-019996-32-BE
• Date of registration: 04/10/2010
• Prospective Registration: Yes
• Primary sponsor: Neovacs SA
• Public title: A phase II, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety and immunogenicity of Neovacs’TNFa-Kinoid in adult subjects with Crohn’s Disease
• Scientific title: A phase II, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety and immunogenicity of Neovacs’TNFa-Kinoid in adult subjects with Crohn’s Disease
• Date of first enrolment: 12/01/2011
• Target sample size: 132
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019996-32
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bulgaria, Croatia, Czech Republic, France, Germany, Hungary, Netherlands, Romania

Contacts

• Name: Chief Medical Officer
• Affiliation: Neovacs

• Name: Chief Medical Officer
• Affiliation: Neovacs

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female aged 18 to 65 years, inclusive.
2. Have had a diagnosis of Crohn’s disease for at least 6 months.
3. Moderate to severe active Crohn’s disease defined as a Crohn’s Disease Activity Index (CDAI) score = 220 and = 450, and presence of mucosal ulcerations in at least 2 segments, or ulcerations on = 10% of the mucosal surface if only one segment is involved.
4. Either have developed secondary resistance to one or two anti-TNFa therapy. Secondary resistance must have followed at least 6 months of continuous anti-TNFa therapy during which a positive clinical response has been observed, according to the Investigator.
and/or
Have developed intolerance to one or two anti-TNFa treatment, provided that the observed adverse events are thought to be unrelated to the primary pharmacological effect of these agents (i.e. TNFa blockade).

Subjects can have received one or more anti-TNFa agent, and must have discontinued this treatment as follows:
•Infliximab: a wash-out period of 8 weeks prior to the first administration of study drug;
•Adalimumab: a wash-out period of 4 weeks prior to the first administration of study drug;
•Certolizumab: a wash-out period of 8 weeks prior to the first administration of study drug;
5. If receiving the medications listed below, must meet the outlined criteria:
•Systemic corticosteroids: up to 25 mg/day of prednisone or equivalent, ongoing for at least 8 weeks, and with a stable dose for at least 2 weeks prior to the first administration of study drug;
•Budesonide: up to 6 mg/day, ongoing for at least 8 weeks, and with a stable dose for at least 2 weeks prior to the first administration of study drug;
•Methotrexate: up to 25 mg/week, ongoing for at least 8 weeks, and with a stable dose for at least 4 weeks prior to the first administration of study drug;
•Azathioprine: up to 2.5 mg/kg/day, ongoing for at least 8 weeks, and with a stable dose for at least 4 weeks prior to the first administration of study drug;
•Mercaptopurine: up to 1.5 mg/kg/day, ongoing for at least 8 weeks, and with a stable dose for at least 4 weeks prior to the first administration of study drug;
•Antibiotics (metronidazole at 15-20 mg/kg per day and/or ciprofloxacin 500 mg bid) are allowed if ongoing for at least 4 weeks, and with a stable dose for at least 2 weeks prior to the first administration of study drug;
•Sulfasalazine and mesalazine ongoing for at least 8 weeks, and with a stable dose of maximum 4g per day for at least 4 weeks prior to the first administration of study drug

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 132
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Primary non-response to a previously received treatment directed against TNFa
Or
Intolerance related to the primary pharmacological effect of anti-TNFa such as for instance, but not limited to, severe or opportunistic infections and demyelinating or autoimmune diseases.
2. History of severe systemic bacterial, fungal, viral, or parasitic infections within the 3 months prior to screening; or the occurrence of any acute infection within 2 weeks of the first administration of study drug.
3. Treatment with more than 2 doses over 30 mg of rectally administered corticosteroids in the 14 days preceding the first administration of study drug.
4. Treatment with immunosuppressive or immunomodulatory drugs, including, but not limited to:
•B-cell depleting therapy (e.g., anti-CD20, anti-CD22) within 1 year of the first administration of study drug;
•Cyclophosphamide within 12 weeks of the first administration of study drug;
•Cyclosporine within 12 weeks of the first administration of study drug;
•TNFa blockers other than infliximab, adalimumab or certolizumab within 12 weeks or 5 half lives of the first administration of study drug, whichever is longer;
•Biological agents other than TNFa blockers within 12 weeks or 5 half lives of the first administration of study drug, whichever is longer.



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

Health Condition(s) or Problem(s) studied

Crohn’s Disease
MedDRA version: 14.0 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: TNF-Kinoid
Product Code: TNF-K
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: Not assigned yet
Current Sponsor code: TNFa-Kinoid or TNFa-K or Kinoid
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Emulsion for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Main Objective: The primary objective of the study is to assess the clinical efficacy of TNF-K in adult subjects with moderate to severe active CD. Specifically, the study will assess the induction of clinical remission (CDAI=150)

Primary end point(s): Efficacy
The same primary efficacy endpoint will be used for the interim and primary analyses, i.e., clinical remission, defined as a CDAI score = 150 points at week 8.

Secondary Objective: • To assess clinical response by CDAI (CDAI-70 and CDAI-100)
• To assess mucosal improvement and healing by ileocolonoscopy
• To assess changes in biological markers of disease activity
• To assess microscopic and biological changes in ileocolonic mucosal tissue
• To evaluate the safety of TNF-K treatment in subjects with moderate to severe active CD
• To evaluate the anti-TNF-a and anti-Keyhole Limpet Hemocyanin (anti-KLH) antibody responses induced by TNF K
• To evaluate the neutralizing anti-TNF-a antibody response induced by TNF-K

Timepoint(s) of evaluation of this end point: Week 8

Secondary Outcome(s)

Secondary end point(s): 1. Clinical responses, defined as a decrease of at least 70 points (CDAI-
70)and at least 100 points (CDAI-100) in the CDAI score at week 8 vs
baseline
2. Endoscopic response, defined as a reduction of at least 50% in the
Crohn's Disease Endoscopic Index of Severity (CDEIS) score or in the
Simple Endoscopic Score for Crohn's Disease (SES-CD) at week 12 vs
baseline
3. Mucosal healing defined as the disappearance of all ulcerations at
week 12
4. Steroid sparing and steroid-free clinical remission by week 28
5. Biological response as defined by a decrease or normalization of
calprotectin levels in stool
6. Biological response as defined by a decrease or normalization of CRP
levels in serum
7. Time to first occurence of clinical response and of clinical remission
8. Changes in the Quality of Life, as measured by the Inflammatory
Bowel Disease Questionnaire (IBDQ).
9. Association between anti-TNFa antibody levels and changes in the
CDAI and the endoscopic scores
10. Association between anti-drug-antibodies (ADA) at baseline and
changes in the CDAI and the endoscopic scores.

Timepoint(s) of evaluation of this end point: 1. week 8
2. week 12
3. week 12
4. week 28
8. 4 and 8 weeks after each study product administration.

Secondary ID(s)

TNF-K-005

Source(s) of Monetary Support

Neovacs