E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
A form of inflammatory bowel disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 objective of this study is to evaluate the efficacy of different doses of rhuMAb Beta7 compared with placebo in patients with moderate to severe UC. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of rhuMAb Beta7 over a treatment period of 10 weeks and a follow-up period of 18 weeks
• To characterize the pharmacokinetic (PK) and immunogenicity (anti-therapeutic antibody/ATA profile) of rhuMAb Beta7 when administered SC across dose levels
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1) ABS4986g (Colonic Biopsy Substudy):
Title: A colonic biopsy substudy in association with rhuMAb BETA7 study ABS4986g to assess changes in immune cell composition in the gut mucosa of patients receiving rhuMAb BETA7
Objectives:
To improve the understanding of the mechanism of action of rhuMAb Beta7
2) ABS4986g (DNA Substudy)
Title: DNA repository substudy in association with rhuMAb BETA7 (PRO145223) study ABS4986g
Objctives: to perform exploratory analyses to generate hypotheses identifying genes associated with treatment response, toxicity, or disease risk. |
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E.3 | Principal inclusion criteria |
- Able and willing to provide written informed consent
- 18-75 years of age
- Males and females with reproductive potential must be willing to use a highly effective method of contraception (e.g., hormonal contraceptive [oral or patch], vaginal ring, intrauterine device, physical barrier, or vasectomized partner) from study start to a minimum of 4 months (approximately 5 half lives) after the final dose of the study drug.
- Diagnosis of moderate to severe UC outpatient with an MCS of >=5, including an endoscopy subscore >= 2; a rectal bleeding subscore >= 1 (see Appendix B); and disease activity a minimum of 25 cm from the anal verge
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E.4 | Principal exclusion criteria |
- Moderate to severe anemia (hemoglobin < 9 g/dL)
- A history or evidence of colonic mucosal dysplasia
- Pregnant or lactating
- Lack of peripheral venous access
- Inability to comply with study protocol, in the opinion of the investigator
- Significant uncontrolled co-morbidity, such as neurological, cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal (GI) disorders
- History of malignancy except completely excised basal cell carcinoma or squamous cell carcinoma of the skin
- Impaired renal function (serum creatinine > 1.5 x upper limit of normal [ULN])
- Impaired hepatic function in the absence of a diagnosis of primary sclerosing cholangitis (serum transaminases > 2.5 x ULN, alkaline phosphatase > 2.5 x ULN, or abnormalities in synthetic liver function tests judged by the investigator to be clinically significant). If the patient has a diagnosis of primary sclerosing cholangitis, serum transaminases > 3 x ULN, alkaline phosphatase > 3 x ULN, or abnormalities in synthetic liver function tests (total bilirubin > 1.5 x ULN) judged by the investigator to be clinically significant.
- Positive tests for antibodies indicating active or prior infection with HIV or hepatitis B (HBV) or C (HCV)
- History of any opportunistic infections within 12 weeks prior to initiation of study treatment
- Demyelinating disease or history of PML
- Any current or recent (within 4 weeks prior to initiation of study treatment) signs or symptoms of infection
- Received any investigational treatment within 12 weeks prior to initiation of study treatment (or within 5 half lives of the investigational product, whichever is greater)
- Previous exposure to rhuMAb Beta7
- History of severe allergic or anaphylactic reactions to chimeric, human or humanized antibodies or fusion proteins |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients in clinical remission at Week 10. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) The proportion of patients with clinical response at Week 6 and Week 10
2) The proportion of patients in clinical remission at Week 6
3) The proportion of patients who achieve an endoscopic score and rectal bleeding score of 0
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 6 and Week 10
2) Week 6
3) Week 10 |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 | No |
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 |
Australia |
Canada |
Israel |
New Zealand |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 CSR will be written following the end of treatment phase (when the last patient completes the Week 28 visit), this would be a total of thirteen months duration. However, patients will continue to be seen for an additional 17 months for PML follow-up, which would be 2 years 6 months total duration. At that point, the PML report will be submitted as an addendum to the CSR. |
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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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |