A Phase 2a Randomised, Placebo-Controlled, Double-Blind, Multi-Center Dose Escalation Study, to Evaluate the Safety, Tolerability, Pharmacodynamics and Efficacy of AG011, in Subjects with Moderatley Active Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-000967-40-NL
• Date of registration: 30/05/2008
• Prospective Registration: Yes
• Primary sponsor: ActoGeniX NV.
• Public title: A Phase 2a Randomised, Placebo-Controlled, Double-Blind, Multi-Center Dose Escalation Study, to Evaluate the Safety, Tolerability, Pharmacodynamics and Efficacy of AG011, in Subjects with Moderatley Active Ulcerative Colitis
• Scientific title: A Phase 2a Randomised, Placebo-Controlled, Double-Blind, Multi-Center Dose Escalation Study, to Evaluate the Safety, Tolerability, Pharmacodynamics and Efficacy of AG011, in Subjects with Moderatley Active Ulcerative Colitis
• Date of first enrolment: 03/11/2008
• Target sample size: 60
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000967-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Netherlands, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
(1) Male or non-pregnant, non-lactating females, 18 years of age or older. Females of child bearing potential must have negative serum or urine pregnancy tests at the screening visit and throughout the study, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the case report form (i.e. tubal ligation, hysterectomy, or post menopausal [defined as a minimum of one year since the last menstrual period]).
(2) Documented diagnosis of UC with a minimum disease extent of 15 cm from the anal verge.
(3) Presence of friability on endoscopy, with minimum of Grade 2 (modified Baron score) changes at approximately 15 cm or more from the anal verge.
(4) Minimum Mayo Clinic Disease Activity Score of 5, with a score of at least 1 on both the stool frequency and rectal bleeding components.
(5) Receiving 5-ASA treatment for at least two months and a stable dose of oral 5 ASA for at least two weeks prior to randomization. Concurrent treatment with prednisone, or equivalent glucocorticoid = 20 mg/day is acceptable as follows:
a. minimum dosing of 4 weeks prior to screening AND
b. stable dose for 2 weeks prior to screening AND
c. expected to remain on a constant dose during the trial.

Use of 5-ASA compounds is not required for those subjects who have failed treatment with 5-ASA compounds, or are allergic or intolerant.
(6) Hepatic function (AST, ALT, total bilirubin, alkaline phosphatase, LDH) = 2 times the upper limit of the normal range.
(7) Adequate renal function, as evidenced by serum creatinine = 1.5 times the upper limit of the normal range.
(8) Hemoglobin = 10 g/dL.
(9) ANC = 1.5 x 10e9/L (1,500 mme3).
(10) Lymphocyte count = 0.1 x 10e3/µL.
(11) Platelet count = 100 x 10e9/L (100,000/mme3).
(12) Ability of subject to participate fully in all aspects of this clinical trial.
(13) Written informed consent must be obtained and documented.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
(1) Exhibiting severe ulcerative colitis as defined by the following criteria:
=6 bloody stools daily with one or more of the following:
a. oral temperature > 37.8 °C or > 100.0 °F,
b. pulse > 90/min,
c. hemoglobin < 10 g/dL.
(2) Crohn’s disease.
(3) History of colectomy or partial colectomy.
(4) C. difficile positive at screening visit or treated for C. difficile within the 4 weeks prior to randomization.
(5) Treatment with antibiotics or probiotics at screening.
(6) Treatment with cyclosporine, methotrexate, azathioprine, 6-MP, infliximab, adalimumab or other immunosuppressants/biologics within 4 weeks prior to randomization.
(7) Use of rectal steroids or 5-ASA enemas within 2 weeks prior to randomization.
(8) Clinical significant active infection.
(9) Known chronic liver disease.
(10) Serious underlying disease other than UC in the opinion of the investigator.
(11) Alcohol or illicit drug consumption, which in the opinion of the investigator, may interfere with the subject’s ability to comply with the study procedures.
(12) Active psychiatric problems, which in the opinion of the investigator, may interfere with the subject’s ability to comply with the study procedures.
(13) History of malignancy other than basal or squamous cell cancer of the skin that has been removed, or carcinoma in situ of the cervix that has been adequately treated.
(14) History of dysplasia in colonic biopsies.
(15) Receiving any investigational therapy or any approved therapy for investigational use within 30 days or 5 half-lives prior to randomization (whichever is longer).
(16) Pregnant or lactating women.
(17) Prior enrolment in the current study and had received study treatment.



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

Health Condition(s) or Problem(s) studied

Moderately Active Ulcerative Colitis
MedDRA version: 9.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis

Intervention(s)

Product Name: AG011 - Enema
Product Code: AG011
Pharmaceutical Form: Powder for rectal suspension
Current Sponsor code: AG011-DS-01
Concentration unit: CFU/g colony forming unit(s)/gram
Concentration type: range
Concentration number: 0.6 x 10e10-1.0 x 10e10
Pharmaceutical form of the placebo: Powder for rectal suspension
Route of administration of the placebo: Rectal use

Product Name: AG011 - Capsules
Product Code: AG011
Pharmaceutical Form: Gastro-resistant capsule, soft
Current Sponsor code: AG011-DS-01
Concentration unit: CFU/g colony forming unit(s)/gram
Concentration type: range
Concentration number: 1.94 x 10e10-3.2 x 10e10
Pharmaceutical form of the placebo: Gastro-resistant capsule, hard
Route of administration of the placebo: Oral use

Product Name: AG011 - Enema
Product Code: AG011
Pharmaceutical Form: Powder for rectal suspension
Current Sponsor code: AG011-DS-01
Concentration unit: CFU/g colony forming unit(s)/gram
Concentration type: range
Concentration number: 0.6 x 10e11-1.0 x 10e11
Pharmaceutical form of the placebo: Powder for rectal suspension
Route of administration of the placebo: Rectal use

Product Name: AG011 - Enema
Product Code: AG011
Pharmaceutical Form: Powder for rectal suspension
Current Sponsor code: AG011-DS-01
Concentration unit: CFU/g colony forming unit(s)/gram
Concentration type: range
Concentration number: 0.3 x 10e12-0.5 x 10e12
Pharmaceutical form of the placebo: Powder for rectal suspension
Route of administration of the placebo: Rectal use

Product Name: AG011 - Capsules
Product Code: AG011
Pharmaceutical Form: Gastro-resistant capsule, hard
Current Sponsor code: AG011-DS-01
Concentration unit: CFU/g colony forming unit(s)/gram
Concentration type: range
Concentration number: 1.94 x 10e11-3.2 x 10e11
Pharmaceutical form of the placebo: Gastro-resistant capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: - To determine the efficacy of AG011 in reducing inflammation in the colon as measured by clinical observations and endoscopy

Main Objective: - To assess the safety and tolerability of AG011 in subjects with moderately active ulcerative colitis (UC),
- To assess for fecal excretion of AG011 and assess environmental containment strategy, and
- To obtain pharmacodynamic (PD) data (biomarkers) of AG011 in a subset of subjects (Belgian subjects only).

Primary end point(s):

Secondary ID(s)

AG011-MDUC-201