Active Ulcerative Colitis MedDRA version: 9.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis
Conditions
Interventions
Product Name: MDX-1100
Product Code: MDX-1100
Pharmaceutical Form: Solution for infusion
Current Sponsor code: MDX-1100
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Conc
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must be 18 years of age or older; 2. Subjects with active UC on stable doses of either 5-ASA, corticosteroids, AZA, and/or 6-MP; 3. Mayo score of 6 to 10 points with moderate to severe disease on endoscopy (Mayo endoscopic score of at least 2) performed = 14 days of study drug administration; 4. Subjects on the following medications may be enrolled into the study if the medications were initiated according to the following schedules before study drug administration and if no dosing changes are anticipated during the study; a. prednisolone = 20 mg daily (or equivalent) (dose must be stable for at least 2 weeks prior to study drug administration); b. 5-ASA (dose must be stable for at least 4 weeks prior to study drug administration); c. AZA or 6-MP (dose must be stable for at least 3 months prior to study drug administration); d. Rectal steroids or 5-ASA (must have been stable for at least 4 weeks prior to study drug administration) - Subjects using rectal medications must have visible disease on sigmoidoscopy at = 20 cm; 5. Screening laboratory values must meet the following criteria: • Hemoglobin = 9.5 gm/dL • WBC = 3000/mm3 • Neutrophils =1.5 x109/L • Platelets =125 x109/L • Prothrombin time (PT) =1.3 X control • Serum creatinine 12 months without menses) or surgically sterile (i.e., by hysterectomy and/or bilateral oophorectomy) or must be using effective contraception (i.e., oral contraceptives, intrauterine device (IUD), double barrier method of condom and spermicide) for at least 4 weeks prior to study drug administration and agree to continue contraception for the duration of their participation in the study. Women of childbearing potential must agree to use contraception for 70 days after their last dose of study drug; and 7. Sexually active male subjects must use a barrier method of contraception during the study and agree to the use of male contraception for at least 180 days after the last dose 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Anti-TNF therapy within 8 weeks before study drug administration; 2. Any experimental therapy = 4 weeks before study drug administration; 3. Prior treatment with any monoclonal antibody or immunoglobulin-based fusion proteins = 8 weeks prior to study treatment; 4. Prior treatment with an anti-CXCL10 antibody; 5. Presence of Cushing’s syndrome; 6. Toxic megacolon or fulminant disease likely to require colectomy; 7. Contraindication to colonoscopy or sigmoidoscopy; 8. Primary or secondary immunodeficiency; 9. Other autoimmune disease such as systemic lupus erythematosus or rheumatoid arthritis, with the exceptions of Sjogren’s Syndrome or organ-specific autoimmune diseases such as vitiligo or well controlled hypo- or hyper-thyroidism; 10. Any history of malignancy, excluding adequately treated and cured basal or squamous cell carcinoma of the skin, or cervical carcinoma in situ; 11. Active major psychiatric disease (subjects with stable depression receiving appropriate medical management will be permitted in the study); 12. Evidence of acute or chronic infection as evidenced by: • Stool culture positive for pathogens and/or Clostridium difficile toxin • Findings on Screening chest radiography such as pulmonary infiltrate(s) or adenopathy • Current treatment for tuberculosis infection, clinical or radiological evidence of active TB (if necessary, confirmed by expert consultation), or for subjects in North America, a positive PPD without prior prophylaxis • Herpes zoster =3 months prior to study drug administration • Active infectious disease requiring i.v. antibiotics within 4 weeks prior to study treatment or oral antibiotics at the time of enrollment • HIV or AIDS • Positive tests for HBV, or HCV indicating active or chronic infection 13. Clinically significant cardiac disease requiring medication, unstable angina, myocardial infarction within 6 months before study drug administration, or congestive heart failure; 14. Arrhythmia requiring active therapy, with the exception of clinically insignificant extrasystoles, or minor conduction abnormalities; 15. History of cerebrovascular disease requiring medication/treatment; 16. Anticoagulation therapy (low-dose aspirin prophylaxis will be permitted) or a known bleeding disorder; 17. Seizure disorder requiring active therapy; 18. Known drug or alcohol abuse; 19. Pregnant or nursing; 20. Any underlying medical condition that in the Principal Investigator’s opinion will make the administration of study drug hazardous to the subject or would obscure the interpretation of study treatment efficacy or safety; or 21. Inability or unwillingness to return for Follow-up visits and comply with study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are to: 1) determine the response rate [defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1] at Day 57 in subjects administered MDX-1100; and 2) assess the tolerability and safety of this MDX-1100 regimen in subjects with active Ulcerative Colitis (UC).;Secondary Objective: The secondary objectives of this study are to: 1) determine the remission rate (defined as a total Mayo score of = 2 points with no individual subscore exceeding 1 point and no blood in stool) at Day 57 in subjects administered MDX-1100; 2) assess Quality of Life (QoL) using the Inflammatory Bowel Disease Questionnaire (IBDQ); 3) determine the mucosal healing score rate at Day 57 for subjects administered MDX-1100; 4) determine the peak and trough pharmacokinetic profile of MDX-1100; and 5) investigate the effects of MDX-1100 on CXCL-10 levels and CXCL-10 responsive markers.;Primary end point(s): The primary efficacy endpoint is the clinical response rate at Day 57. The clinical response is defined as a decrease from baseline (Screening) in the total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1. | — |
Countries
Czech Republic, Hungary, Latvia
Outcome results
None listed