Moderately Active Ulcerative Colitis Clinical Trial
Official title:
A Phase 2a Randomized, Placebo-Controlled, Double-Blind, Multi-Center Dose Escalation Study, to Evaluate the Safety, Tolerability, Pharmacodynamics and Efficacy of AG011, in Subjects With Moderately Active Ulcerative Colitis
The purpose of this study is to verify the safety and tolerability of AG011 (genetically modified L. lactis that has been engineered to secrete human Interleukin-10), and to determine whether AG011 can successfully treat the symptoms of moderately active Ulcerative Colitis (UC).
| Status | Completed |
| Enrollment | 60 |
| Est. completion date | September 2009 |
| Est. primary completion date | September 2009 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - 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]). - Documented diagnosis of UC with a minimum disease extent of 15 cm from the anal verge. - Presence of friability on endoscopy, with minimum of Grade 2 (modified Baron score) changes at approximately 15 cm or more from the anal verge. - Minimum Mayo Clinic Disease Activity Score of 5, with a score of at least 1 on both the stool frequency and rectal bleeding components. - 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: minimum dosing of 4 weeks prior to screening AND stable dose for 2 weeks prior to screening AND 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. - Hepatic function (AST, ALT, total bilirubin, alkaline phosphatase, LDH) = 2 times the upper limit of the normal range. - Adequate renal function, as evidenced by serum creatinine = 1.5 times the upper limit of the normal range. - Hemoglobin = 10 g/dL. - ANC = 1.5 x 10E9/L (1,500 mm3). - Lymphocyte count = 0.1 x 10E3/µL. - Platelet count = 100 x 10E9/L (100,000/mm3). - Ability of subject to participate fully in all aspects of this clinical trial. - Written informed consent must be obtained and documented. Exclusion Criteria: - Exhibiting severe ulcerative colitis as defined by the following criteria: = 6 bloody stools daily with one or more of the following: oral temperature > 37.8 °C or > 100.0 °F, pulse > 90/min, hemoglobin < 10 g/dL. - Crohn's disease. - History of colectomy or partial colectomy. - Clostridium (C.) difficile positive at screening visit or treated for C. difficile within the 4 weeks prior to randomization - Treatment with antibiotics or probiotics at screening - Treatment with cyclosporine, methotrexate, azathioprine, 6-MP, infliximab, adalimumab or other immunosuppressants/biologics within 4 weeks prior to randomization - Use of rectal steroids or 5-ASA enemas within 2 weeks prior to randomization. - Clinically significant active infection. - Known chronic liver disease. - Serious underlying disease other than UC in the opinion of the investigator. - 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 - Active psychiatric problems, which in the opinion of the investigator, may interfere with the subject's ability to comply with the study procedures. - 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. - History of dysplasia in colonic biopsies. - Receiving any investigational therapy or any approved therapy for investigational use within 30 days or 5 half-lives prior to randomization (whichever is longer). - Pregnant or lactating women. - Prior enrollment in the current study and had received study treatment. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Imelda Bonheiden | Bonheiden | |
| Belgium | UCL St. Luc | Brussels | |
| Belgium | UZ Antwerpen | Edegem | |
| Belgium | UZ Gent | Ghent | |
| Belgium | AZ Groeninge Campus St.-Niklaas | Kortrijk | |
| Belgium | UZ Leuven | Leuven | |
| Canada | Hotel Dieu Hospital | Kingston | Ontario |
| Canada | LHSC - South Street Campus | London | Ontario |
| Canada | LHSC - University Campus | London | Ontario |
| Canada | Ottawa Hospital General Campus | Ottawa | Ontario |
| Canada | Hôpital St-Sacrement | Quebec | |
| Canada | Mount Sinai Hospital | Toronto | Ontario |
| Canada | GI Research Institute | Vancouver | British Columbia |
| Canada | The office of Dr. Donald Daly | Victoria | British Columbia |
| Netherlands | Leiden University Medical Center | Leiden | |
| Sweden | Lund University Hospital | Lund | |
| Sweden | Orebro University Hospital | Orebro | |
| Sweden | Sophiahemmet | Stockholm |
| Lead Sponsor | Collaborator |
|---|---|
| ActoGeniX N.V. |
Belgium, Canada, Netherlands, Sweden,
Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP, van Deventer SJ, Neirynck S, Peppelenbosch MP, Steidler L. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin Gastroenterol Hepatol. 2006 Jun;4(6):754-9. Epub 2006 May 22. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | SAFETY: Adverse Events | day 1, 8 15, 22, 29, 57 | Yes | |
| Primary | SAFETY: Physical Examination (complete or brief) | day -7, 1, 8, 15, 22, 29 | Yes | |
| Primary | SAFETY: Vital signs | day -7, 1, 8, 15, 22, 29, 57 | Yes | |
| Primary | SAFETY: Clinical Laboratory Tests (hematology, serum chemistry, urinalysis) | day -7, 1, 8, 15, 22, 29, 57 | Yes | |
| Primary | SAFETY: Analysis of hIL-10 (systemic exposure) and anti-hIL-10 antibodies (immunogenicity) in plasma | day 1, day 29 | Yes | |
| Primary | SAFETY: Stool Diary | From day -7 until day 29 | Yes | |
| Primary | SAFETY: Other Safety Measures (Stool samples for culture, ova and parasite evaluation and Clostridium difficile assay. | day -7 | Yes | |
| Primary | BIOLOGICAL CONTAINMENT: Evaluation of living, genetically modified micro-organisms in stool samples | day 1, 8, 36 | No | |
| Primary | PHARMACODYNAMICS: Biomarkers in blood and colon biopsy samples | day -7, 29 | No | |
| Secondary | EFFICACY: Flexible sigmoidoscopy (assessment of inflammation) | Day -7, 29 | No | |
| Secondary | EFFICACY: Histological assessment of inflammation (biopsy samples) | Day -7, 29 | No | |
| Secondary | EFFICACY: Disease activity assessments (MCDAS, UCCS, Investigator and Subject Global Ratings) | Day -7, 1, 8, 15, 22, 29, 57 | No | |
| Secondary | EFFICACY: Laboratory assessments (CRP and fecal calprotectin) | Day 1, 15, 29, 57 | No |