E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerative Colitis and Crohn’s Disease |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013099 |
E.1.2 | Term | Disease Crohns |
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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 |
Primary Objective
• To determine the safety profile of long-term MLN0002 treatment
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E.2.2 | Secondary objectives of the trial |
Resource Utilization and Patient Reported Outcome Objectives
• To determine the effect of long-term MLN0002 treatment on time to major IBD-related events (hospitalizations, surgeries, and IBD-related procedures)
• To determine the effect of long-term MLN0002 treatment on health-related quality of life (QOL) measurements
Exploratory Objective
• To obtain data regarding the effect of long-term MLN0002 treatment on maintaining clinical response and remission
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Voluntarily able to give informed consent.
2. Previous treatment in Study C13004, Study C13006 or Study C13007 that, in the opinion of the investigator, was well tolerated. Patients who withdrew early from C13006 or C13007 must have withdrawn due to one of the following:
• Sustained Nonresponse for patients with UC in C13006: Failure to achieve a clinical response (2 point and 25% improvement in partial Mayo score) by Week 14 and a minimum partial Mayo score of ≥5 points
• Sustained Nonresponse for patients with CD in C13007: Failure to achieve a clinical response (70 point improvement in CDAI score) by Week 14 and a minimum CDAI score of 220 points
• Disease Worsening for patients with UC in C13006: An increase in partial Mayo score of ≥3 points on 2 consecutive visits from the Week 6 value (or an increase to 9 points on 2 consecutive visits if the Week 6 value >6) and a minimum partial Mayo score of ≥5 points
• Disease Worsening for patients with CD in C13007: A ≥100 point increase in CDAI score on 2 consecutive visits from the Week 6 value at any study visit and a minimum CDAI score of 220 points
• Rescue medications for patients in C13006 and C13007: Any new medication or any increase in dose of a baseline medication required to treat new or unresolved UC or CD symptoms (other than antidiarrheals for control of chronic diarrhea)
3. The first dose of MLN0002 in this study (ie, Week 0) must occur not more than 5 weeks after the last dose of study drug in the previous MLN0002 study.
4. Female patients must:
• be post-menopausal for at least 1 year before the screening visit, OR
• be surgically sterile, OR
• (if they are of childbearing potential) agree to practice 2 effective methods of contraception, at the same time, from four weeks before the first dose of study drug through 6 months after the last dose of study drug, OR
• agree to completely abstain from heterosexual contact.
Male patients, even if surgically sterilized (ie, status post-vasectomy), must:
• agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, OR
• agree to completely abstain from heterosexual contact.
5. Patients with extensive colitis or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of enrollment
6. Patients with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance.
7. May be receiving a therapeutic dose of the following drugs:
a. Oral 5-ASA compounds b. Oral corticosteroid therapy (prednisone at a stable dose ≤30 mg/day, budesonide at a stable dose ≤9 mg/day, or equivalent steroid) c. Topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories d. Probiotics (eg, Culturelle, Saccharomyces boulardii) e. Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea f. Antibiotics used for the treatment of CD (ie, ciprofloxacin, metronidazole).
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E.4 | Principal exclusion criteria |
1. Female patients who are lactating or pregnant
2. Required surgical intervention for IBD during or after participation in a prior MLN0002 study, currently require surgical intervention for IBD, or are anticipated to require surgical intervention for IBD during this study
3. Any live vaccinations within 30 days prior to MLN0002 administration except for the influenza vaccine
4. Development of any new, unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurologic, oncologic, or other medical disorder during or after participation in a prior MLN0002 study that, in the opinion of the investigator, would confound the study results or compromise patient safety
5. Withdrawal from a previous MLN0002 study due to a study-drug related AE
6. Active psychiatric or substance abuse problems that, in the investigator’s opinion, may interfere with compliance with the study procedures
7. Unable to attend all the study visits or comply with study procedures
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoints
• SAEs, AEs, vital signs, standard laboratory tests (clinical chemistry, hematology, coagulation, urinalysis, and HAHA), and electrocardiograms (ECGs)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 219 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |