Study to Evaluate the Efficacy and Safety of Oral VB-201 in Subjects with Mild to Moderate Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2012-003974-18-HU
• Date of registration: 28/09/2012
• Prospective Registration: Yes
• Primary sponsor: Vascular Biogenics Ltd.
• Public title: Study to Evaluate the Efficacy and Safety of Oral VB-201 in Subjects with Mild to Moderate Ulcerative Colitis
• Scientific title: A Randomized, Double-Blind, 12-Week, Placebo-Controlled Study Followed by a 12-Week Extension Phase Without Placebo to Evaluate the Efficacy and Safety of Oral VB-201 in Subjects with Mild to Moderate Ulcerative Colitis
• Date of first enrolment: 10/12/2012
• Target sample size: 110
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003974-18
• 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: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Bulgaria, Hungary

Contacts

• Name: VBL
• Affiliation: Vascular Biogenics Ltd.

• Name: VBL
• Affiliation: Vascular Biogenics Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
Fully understand all elements of and have signed and dated the written Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent before initiation of protocol-specified procedures;
2. Male or female, =18 years of age, who has a diagnosis of active UC for at least 6 months prior to screening;
3. A rectal/colonic biopsy obtained previously and consistent with a diagnosis of UC (if not previously obtained, biopsies should be done as part of screening endoscopy);
4. Endoscopy (flexible sigmoidoscopy unless surveillance colonoscopy is clinically indicated) confirming diagnosis of UC within 2 weeks prior to randomization;
5. Modified Mayo score of 4 to 10 points (mild to moderate) and Mayo endoscopic score of at least 2 to be confirmed by Central Reader endoscopy video;
6. Active UC despite previous treatment with at least one 5-aminosalicylic acid (5-ASA) compound at a dose of =2000 mg/day for at least 4 weeks or documented intolerance to such therapy;
7. For a female subject; either: - subject is of non-childbearing potential, defined as: menopause with amenorrhea >2 years, hysterectomy, or bilateral oophorectomy
OR
- agrees to continue to use adequate contraception (implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], sexual abstinence or vasectomised partner
Male subject must use at least one method of contraception (e.g., condom) throughout the study; ) throughout the study and for at least one month following termination and have a negative pregnancy test at screening and before the first dose of study drug;
8. In the opinion of the Investigator, the subject will be compliant and have a high probability of completing the study and all required procedures.
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 104
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion criteria:
1.Diagnosis of indeterminate colitis, Crohn’s disease, or clinical findings suggestive of Crohn’s disease (fistula or granulomas on biopsy) or microscopic colitis (collagenous colitis or lymphocytic colitis);
2. Subject whose symptoms are likely caused by factors other than inflammatory UC, including infection or irritable bowel syndrome (IBS)
3. History of dysplasia on colonic biopsy;
Subject with = 8 year history of pancolitis or = 15 year history of left sided colitis unless a colonoscopy with surveillance biopsies to screen for colon cancer has been performed within the past year. If the subject has not had this procedure within the past year, the subject will be required to have a colonoscopy rather than flexible sigmoidoscopy at Screening;
5. Subject = 50 years of age who has not had a colonoscopy to screen for colorectal polyps and colon cancer within the past 5 years. The subject will be required to have a colonoscopy rather than flexible sigmoidoscopy at Screening;
6. Subject who has had any prior surgical resection of any part of the colon excluding the appendix;
7. Subject who has been hospitalized for a UC-related event within 30 days prior to Screening;
8. Subject who received any investigational drug within 30 days or five half-lives of Screening;
9. Previous participation in a VB-201 study;
10. Previous treatment with any biologic product including investigational biologic products within one year prior to baseline visit
11. Concomitant and prior medications: subjects should be excluded if they are taking:
- Systemic corticosteroids unless they have been on a stable dose of one of the following for at least 4 weeks prior to the Baseline Visit:
• Prednisone up to 20 mg/day or equivalent
• Budesonide up to 9 mg/day
If recently discontinued, must have stopped at least 4 weeks prior to the Baseline Visit;
- Azathioprine/6-mercaptopurine/methotrexate unless the subject has been on such treatment for at least 4 months prior to the Baseline Visit and at a stable dose for at least 8 weeks prior to the Baseline Visit. If recently discontinued, the subject must have stopped at least 4 weeks or 5 half-lives prior to the Baseline Visit;
- Any other immunosuppressants (e.g. tacrolimus, cyclosporine, mycophenolate mofetil, or leflunomide). If recently discontinued, the subject must have stopped at least 4 weeks or 5 half-lives (which ever is greatest) prior to the Baseline Visit;
- Oral 5-ASA compounds unless the subject has been on a stable dose at least 4 weeks prior to the Baseline Visit. If recently discontinued, the subject must have stopped at least 4 weeks prior to the Baseline Visit;
- Rectally administered corticosteroids or 5-ASA are excluded for at least 14 days prior to the Baseline Visit and throughout the study;
- Antibiotics for the treatment of UC within 14 days of the Baseline Visit and throughout the study (Exception: antibiotics are permitted to treat infections outside of the gastrointestinal tract);
- Probiotics within 14 days of the Baseline Visit and throughout the study.
12. The subject has with a stool culture positive for pathogenic ova or parasites, enteric pathogens or Clostridium difficile toxin at the Screening Visit (if initially positive, subjects treated for C. difficile may be re-screened once);
13. The subject has a known allergy or sensitivity to the study treatment(s) or to any of the excipients contained in the study drug formulation (see list of ingredients in the Investigator’s Brochure);
14. An

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

Health Condition(s) or Problem(s) studied

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

Mild to Moderate Ulcerative Colitis
MedDRA version: 16.0 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Code: VB-201
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not applicable
CAS Number: 630112-41-3
Current Sponsor code: VB-201
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): - Safety will be assessed based on all subjects in the study who have received at least one dose of study drug (Safety Population):
• Physical examinations;
• Adverse events (AEs);
• Vital signs;
• Laboratory values – clinical chemistry, hematology, urinalysis;
• Electrocardiograms (ECGs).
- The primary efficacy endpoint for the Base Phase is proportion of subjects in remission in arm A group compared to arm B at the Week 12 Visit.
Remission is defined as all of the following:
1. A total Modified Mayo score of 2 points or lower;
2. No individual sub-score exceeding 1 point;
3. No use of any prohibited medications;
4. No increase in dose of any stable UC related concomitant medications

The primary efficacy endpoint for the Extension Phase will compare the proportions (%) of subjects achieving a Modified Mayo Score indicating remission between Week 24 in arm A and Week 12 in arm B.

Main Objective: - Safety Objective
• To examine the safety and tolerability of up to 24 weeks’ treatment with VB-201 or placebo in subjects with UC
- Efficacy Objective
• Base Phase: To examine the effect of treatment with VB-201 80 mg BID compared to placebo (initial 12 weeks) on measures of disease activity in subjects with UC.
• Extension Phase: To examine the effect of longer-term treatment with VB-201 (24 weeks) on measures of disease activity in subjects with UC.

Timepoint(s) of evaluation of this end point: Safety - every visit
Efficacy - Week 12
Extension phase efficacy - Week 24

Secondary Objective: No secondary objectives were established

Secondary Outcome(s)

Secondary end point(s): In addition to the primary efficacy analysis, comparisons will be performed between the two arms for the following Base Phase (Day 1- Week 12) secondary efficacy outcomes:
1. At Week 12, the proportion of responders in each arm; response is defined as all of the following:
• =3-points and at least 30% decrease from the Baseline Visit Modified Mayo Score;
• =1-point decrease from the Baseline Visit in the rectal bleeding component of the Modified Mayo Score or an absolute sub-score for rectal bleeding of 0 or 1;
• No use of any prohibited medications;
• No increase in dose of any stable UC related concomitant medications.
2. At Week 12, the proportion of subjects in each arm with a 2-point or greater decrease in the Modified Mayo score.
3. Change from Baseline to Week 12 in the modified Baron score, an ordered categorical variable, in arm A compared to arm B.
4. At Week 12, the proportion of subjects in each arm with mucosal healing, defined as all of the following:
• An absolute sub-score for endoscopy of 0 or 1 (any degree of friability will receive a score of at least 2);
• No use of any prohibited medications;
• No increase in dose of any stable UC related concomitant medications.


Extension Phase Secondary Efficacy Endpoints:
The following endpoints will be analyzed:
1. The proportion of responders at Week 24.
2. The proportion of subjects at Week 24 with a 2-point or greater decrease in the Modified Mayo score.
3. Change from Baseline to Week 24 in the modified Baron score, an ordered categorical variable.
4. At Week 24: The proportion of subjects in each arm with mucosal healing, defined as all of the following:
• An absolute sub-score for endoscopy of 0 or 1 (any degree of friability will receive a score of at least 2);
• No use of any prohibited medications;
• No increase in dose of any stable UC related concomitant medications.
For each of the above secondary endpoints, the arm A Week 24 result will be compared to: a) the arm B endpoint result at Week 12; b) the arm A result for this endpoint at Week 12. The arm B endpoint result at Week 24 will be compared to the arm B endpoint result at Week 12.
Additionally, the proportion (%) of subjects achieving a Modified Mayo Score indicating remission at Week 24 in arm A will be compared to the arm A remission result at Week 12; the arm B remission results at Week 24 will be compared to the arm B remission results at Week 12.
An additional secondary analysis will compare the proportion of subjects in remission at Week 12 in arm A combined with those in remission at Week 24 in arm B to the proportion in remission at Week 12 in arm B.

Timepoint(s) of evaluation of this end point: Base Phase Secondary Endpoints: Week 12
Extension Phase Secondary Efficacy Endpoints: Week 24

Secondary ID(s)

VB-201-064

Source(s) of Monetary Support

Vascular Biogenics Ltd.