E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Ulcerative Colitis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 be met: • 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 <2 mg/dL • AST ≤2 X upper limit of normal • ALT ≤2 X upper limit of normal 6. Women must be postmenopausal (> 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. |
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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. The clinical response rate is defined as proportion of subjects in each treatment group who had a clinical response. The clinical response rate will be summarized using descriptive statistics and analyzed using Fisher’s exact test between the treatment groups. The 95% confidence interval for difference in response rates will be presented. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is the last visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |