A Phase 2a Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Efficacy of AG011 in Ulcerative Colitis
This study has been completed.
Sponsor:
ActoGeniX N.V.
Information provided by:
ActoGeniX N.V.
ClinicalTrials.gov Identifier:
NCT00729872
First received: August 4, 2008
Last updated: September 9, 2009
Last verified: September 2009
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Purpose
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).
| Condition | Intervention | Phase |
|---|---|---|
|
Moderately Active Ulcerative Colitis |
Biological: AG011 Other: Placebo |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by ActoGeniX N.V.:
Primary Outcome Measures:
- SAFETY: Adverse Events [ Time Frame: day 1, 8 15, 22, 29, 57 ] [ Designated as safety issue: Yes ]
- SAFETY: Physical Examination (complete or brief) [ Time Frame: day -7, 1, 8, 15, 22, 29 ] [ Designated as safety issue: Yes ]
- SAFETY: Vital signs [ Time Frame: day -7, 1, 8, 15, 22, 29, 57 ] [ Designated as safety issue: Yes ]
- SAFETY: Clinical Laboratory Tests (hematology, serum chemistry, urinalysis) [ Time Frame: day -7, 1, 8, 15, 22, 29, 57 ] [ Designated as safety issue: Yes ]
- SAFETY: Analysis of hIL-10 (systemic exposure) and anti-hIL-10 antibodies (immunogenicity) in plasma [ Time Frame: day 1, day 29 ] [ Designated as safety issue: Yes ]
- SAFETY: Stool Diary [ Time Frame: From day -7 until day 29 ] [ Designated as safety issue: Yes ]
- SAFETY: Other Safety Measures (Stool samples for culture, ova and parasite evaluation and Clostridium difficile assay. [ Time Frame: day -7 ] [ Designated as safety issue: Yes ]
- BIOLOGICAL CONTAINMENT: Evaluation of living, genetically modified micro-organisms in stool samples [ Time Frame: day 1, 8, 36 ] [ Designated as safety issue: No ]
- PHARMACODYNAMICS: Biomarkers in blood and colon biopsy samples [ Time Frame: day -7, 29 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- EFFICACY: Flexible sigmoidoscopy (assessment of inflammation) [ Time Frame: Day -7, 29 ] [ Designated as safety issue: No ]
- EFFICACY: Histological assessment of inflammation (biopsy samples) [ Time Frame: Day -7, 29 ] [ Designated as safety issue: No ]
- EFFICACY: Disease activity assessments (MCDAS, UCCS, Investigator and Subject Global Ratings) [ Time Frame: Day -7, 1, 8, 15, 22, 29, 57 ] [ Designated as safety issue: No ]
- EFFICACY: Laboratory assessments (CRP and fecal calprotectin) [ Time Frame: Day 1, 15, 29, 57 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 60 |
| Study Start Date: | July 2008 |
| Study Completion Date: | September 2009 |
| Primary Completion Date: | September 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
AG011: low dose
|
Biological: AG011
Capsules (low, mid or high dose), twice daily for 28 days, combined with Enema (low, mid or high dose respectively), once daily for 28 days.
|
|
Placebo Comparator: 2
Placebo: low dose
|
Other: Placebo
Capsules (matching placebo for low, mid or high dose), twice daily for 28 days, combined with Enema (matching placebo for low, mid or high dose respectively), once daily for 28 days.
|
|
Experimental: 3
AG011: mid dose
|
Biological: AG011
Capsules (low, mid or high dose), twice daily for 28 days, combined with Enema (low, mid or high dose respectively), once daily for 28 days.
|
|
Placebo Comparator: 4
Placebo: mid dose
|
Other: Placebo
Capsules (matching placebo for low, mid or high dose), twice daily for 28 days, combined with Enema (matching placebo for low, mid or high dose respectively), once daily for 28 days.
|
|
Experimental: 5
AG011: high dose
|
Biological: AG011
Capsules (low, mid or high dose), twice daily for 28 days, combined with Enema (low, mid or high dose respectively), once daily for 28 days.
|
|
Placebo Comparator: 6
Placebo: high dose
|
Other: Placebo
Capsules (matching placebo for low, mid or high dose), twice daily for 28 days, combined with Enema (matching placebo for low, mid or high dose respectively), once daily for 28 days.
|
Detailed Description:
The purpose of this study is to verify the safety and tolerability of AG011 and to determine whether AG011 can successfully treat the symptoms of Ulcerative Colitis (UC). Three different dosages will be used in reference to a placebo.
AG011 is an experimental medication. It has been developed as potential treatment for moderately active UC.
AG011 is the clinical formulation of a genetically modified L. lactis that has been engineered to secrete human Interleukin-10 (hIL-10). By delivering hIL-10 locally at inflamed tissue in the intestine, it is believed that, compared to hIL-10 given by injection, the effectiveness may be increased, with fewer adverse effects.
Study medication will be provided in capsule and enema (topical rectal application) forms by ActoGeniX NV.
Subjects will be entered sequentially into one of three dose groups, starting from the lowest dose group. Within each of the first two dose groups, 15 subjects will be entered. Within the highest dose group, 30 subjects will be entered. Within each dose group, subjects will be randomly assigned in a 2:1 ratio to receive either AG011 or placebo for 28 days.
Timely monitoring of safety data is planned for the study, such that subject enrollment can continue without interruption for the purpose of data collection between dose groups. Safety and tolerability will be closely monitored by the Clinical Safety Specialist (CSS) assigned to the study. The CSS will review adverse events and laboratory safety data and report any safety concerns to the Sponsor and a Data Safety Monitoring Committee (DSMC).
At least 8 subjects must have safely completed study treatment for 28 days at a specific dose level, prior to escalation to the next dose group. The DSMC will convene to assess safety data when 8 subjects have completed study treatment for 28 days at the specific dose level. The role of the DSMC for the study will be complete when all subjects in the study have completed study treatment.
For those patients randomized within the active group, UC symptoms could improve. As a result of the information gathered by this study, the knowledge and understanding of UC could improve.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00729872
Locations
| Belgium | |
| Imelda Bonheiden | |
| Bonheiden, Belgium, B-2820 | |
| UCL St. Luc | |
| Brussels, Belgium | |
| UZ Antwerpen | |
| Edegem, Belgium, B-2650 | |
| UZ Gent | |
| Ghent, Belgium, B-9000 | |
| AZ Groeninge Campus St.-Niklaas | |
| Kortrijk, Belgium | |
| UZ Leuven | |
| Leuven, Belgium, B-3000 | |
| Canada, British Columbia | |
| GI Research Institute | |
| Vancouver, British Columbia, Canada, V6Z 2K5 | |
| The office of Dr. Donald Daly | |
| Victoria, British Columbia, Canada | |
| Canada, Ontario | |
| Hotel Dieu Hospital | |
| Kingston, Ontario, Canada | |
| LHSC - University Campus | |
| London, Ontario, Canada, N6A 5A5 | |
| LHSC - South Street Campus | |
| London, Ontario, Canada, N6A 4G5 | |
| Ottawa Hospital General Campus | |
| Ottawa, Ontario, Canada | |
| Mount Sinai Hospital | |
| Toronto, Ontario, Canada | |
| Canada | |
| Hôpital St-Sacrement | |
| Quebec, Canada, G1S 4L8 | |
| Netherlands | |
| Leiden University Medical Center | |
| Leiden, Netherlands, 2333 ZA | |
| Sweden | |
| Lund University Hospital | |
| Lund, Sweden, SE-221 85 | |
| Orebro University Hospital | |
| Orebro, Sweden, SE-701 85 | |
| Sophiahemmet | |
| Stockholm, Sweden, SE- 114 86 | |
Sponsors and Collaborators
ActoGeniX N.V.
Investigators
| Study Chair: | Bernard Coulie, MD PhD | Chief Medical Officer ActoGeniX NV |
| Study Director: | Annegret Van der Aa, PhD | Project Manager ActoGeniX NV |
| Principal Investigator: | Severine Vermeire, MD PhD | UZ Leuven, Belgium |
| Principal Investigator: | Geert D'Haens, MD PhD | Imelda Bonheiden, Belgium |
| Principal Investigator: | Martine De Vos, MD PhD | UZ Gent, Belgium |
| Principal Investigator: | Tom Moreels, MD PhD | UZ Antwerpen, Belgium |
| Principal Investigator: | Daan Hommes, MD PhD | Leiden University Medical Center |
| Principal Investigator: | Erik Hertervig, MD PhD | Lund University Hospital, Sweden |
| Principal Investigator: | Curt Tysk, MD PhD | Orebro University Hospital, Sweden |
| Principal Investigator: | Robert Lofberg, MD PhD | Karolinska Institutet, Sweden |
| Principal Investigator: | Pierre Paré, MD PhD | Hôpital St-Sacrement Quebec, Canada |
| Principal Investigator: | William Barnett, MD PhD | LHSC - University Campus London, Canada |
| Principal Investigator: | Brian Bressler, MD PhD | GI Research Institute Vancouver, Canada |
| Principal Investigator: | James Gregor, MD PhD | LHSC - South Street Campus London, Canada |
| Principal Investigator: | Hillary Steinhart, MD PhD | Mount Sinai Hospital, Canada |
| Principal Investigator: | Richmond Sy, MD PhD | Ottawa Hospital General Campus, Canada |
| Principal Investigator: | William Depew, MD PhD | Hotel-Dieu Hospital Kingston, Canada |
| Principal Investigator: | Donald Daly, MD PhD | Victoria BC, Canada |
| Principal Investigator: | Philippe Vergauwe, MD PhD | AZ Groeninge Campus St.-Niklaas Kortrijk, Belgium |
| Principal Investigator: | Olivier Dewit, MD PhD | UCL St. Luc Brussels, Belgium |
More Information
Publications:
| Responsible Party: | Bernard Coulie, VP Research and Development, ActoGeniX |
| ClinicalTrials.gov Identifier: | NCT00729872 History of Changes |
| Other Study ID Numbers: | AG011-MDUC-201 |
| Study First Received: | August 4, 2008 |
| Last Updated: | September 9, 2009 |
| Health Authority: | Belgium: Commissie Medische Ethiek UZ Leuven (leading EC), Federal Agency for Medicines and Health Products, Division of Biosafety and Biotechnology Netherlands: Netherlands Ministry of Housing, Spatial planning and the Environment, Central Committee on Research involving Human Subjects, bureau GGO Sweden: Medical Products Agency, Regional Ethical Examining Board in Lund second division (leading EC) Canada: Health Canada, Research Ethics Board |
Keywords provided by ActoGeniX N.V.:
|
AG011 Ulcerative Colitis human Interleukin-10 |
Additional relevant MeSH terms:
|
Colitis Colitis, Ulcerative Ulcer Gastroenteritis Gastrointestinal Diseases |
Digestive System Diseases Colonic Diseases Intestinal Diseases Inflammatory Bowel Diseases Pathologic Processes |
ClinicalTrials.gov processed this record on June 18, 2013