| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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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 |
Part 1: Dose-ranging
• To evaluate the dose response of IV golimumab induction regimens in subjects with moderately to severely active UC.
• To select IV induction regimen(s) of golimumab, based on safety and efficacy, for continued development in Part 2.
• To provide the target study population to be evaluated in the 1-year golimumab maintenance study (C0524T18, EudraCT 2006-003399-37).
Part 2: Dose-confirming
• To evaluate the efficacy of IV induction regimens of golimumab in inducing clinical response in subjects with moderately to severely active UC.
• To evaluate the safety of IV induction regimens of golimumab in subjects with moderately to severely active UC. |
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| E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of IV induction regimens of golimumab in inducing clinical remission.
To evaluate the efficacy of IV induction regimens of golimumab in inducing mucosal healing.
To evaluate the efficacy of IV induction regimens of golimumab in improving disease-specific health-related quality of life.
To provide the target study population to be evaluated in the 1-year golimumab maintenance study (C0524T18). |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Are men or women 18 years of age or older.
2.Had UC diagnosed prior to screening.
3.Must either be currently receiving treatment with, or have a history of having failed to respond to, or tolerate, at least 1 of the following therapies: oral corticosteroids, 6-MP, or AZA.
4.Prior to the screening endoscopy or the subject’s first entry in the Mayo diary cards, several conditions must be met. See page 19 and 20 of the protocol.
5.Must be ambulatory and have moderately to severely active UC confirmed during the screening sigmoidoscopy by a >_ 2 endoscopy subscore of the Mayo score.
6.Must have a diagnosis of UC confirmed by a biopsy collected at the screening endoscopy procedure or have a previous biopsy result obtained within the last year that is consistent with the diagnosis of UC.
7.Have moderately to severely active UC, defined as a baseline (Week 0) Mayo score of 6 to 12, inclusive.
8.All subjects >_ 45 years of age, must either have had a colonoscopy to assess for the presence of adenomatous polyps within 5 years of the first administration of study agent or a colonoscopy to assess for the presence of adenomatous polyps at the screening visit. The adenomatous polyps must be removed prior to the first administration of study agent.
9.All subjects who have had extensive colitis for >_ 8 years, or disease limited to the left side of the colon for >_10 years, must either have had a colonoscopy to assess the presence of dysplasia within 1 year prior to the first administration of study agent or a colonoscopy to assess the presence of malignancy at the screening visit.
10.The investigator has discussed with the subject the information contained within the informed consent regarding anti-TNF therapies and the potential risk of cancer, and has reviewed with the subject country-specific guidance (local practice) on cancer screening and the impact of life-style choices (eg, smoking) on the risk of developing cancer.
11.Are considered eligible according to the specific TB screening criteria. See page 20 and 21 of the protocol.
12.Have negative stool results for enteric pathogens.
13.During the study and for 6 months after receiving the last administration of study agent, women of childbearing potential or men capable of fathering children must agree to use adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization). Women of childbearing potential must test negative for pregnancy at screening and at Week 0.
14.Have screening detailed laboratory test results. See page 21 of the protocol.
15.Must be able and willing to adhere to the study visit schedule and comply with other protocol requirements.
16.Are capable of providing informed consent, which must be obtained prior to any study-related procedures.
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| E.4 | Principal exclusion criteria |
1.Have severe extensive colitis, as defined in protocol.
2.Have UC limited to the rectum only or to < 20 cm of the colon.
3.Presence of a stoma.
4.Presence or history of a fistula.
5.Require, or required within the 2 months prior to screening, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or pancreatic abscess requiring surgical drainage, or other conditions possibly confounding the evaluation of benefit from study agent treatment.
6.Presence of symptomatic colonic or small bowel obstruction, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy).
7.History of extensive colonic resection (eg, less than 30 cm of colon remaining) that would prevent adequate evaluation of the effect of study agent on clinical disease activity.
8.History of colonic mucosal dysplasia.
9.Presence on screening endoscopy of adenomatous colonic polyps, if not removed prior to study entry, or history of adenomatous colonic polyps that were not removed.
Concomitant or previous medical therapies received:
10.Have ever received biologic therapy targeted at TNFa (eg, infliximab, etanercept, certolizumab, adalimumab).
11.Have ever received natalizumab or other agents that target alpha-4-integrin.
12.Have ever received agents that deplete B cells (eg, rituximab) or T cells (eg, alemtuzumab, visilizumab).
13.Are receiving oral corticosteroids at a dose of greater than 40 mg of prednisone or its equivalent per day.
14.Have received cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 8 weeks prior to first administration of study agent.
15.Have a known hypersensitivity to human immunoglobulin proteins or other components of golimumab.
16.Have used any investigational drug within 4 weeks prior to first administration of study agent or within 5 half lives of the investigational agent, whichever is longer.
17.Have used apheresis (ie, Adacolumn apheresis) within 2 weeks prior to first administration of study agent.
Infections or predisposition to infections:
18.Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening.
19.Have a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, recurrent urinary tract infection (eg, recurrent pyelonephritis, chronic cystitis), an open, draining, or infected skin wound, or an ulcer.
20.Have immune deficiency syndrome (eg, severe combined immunodeficiency syndrome [SCIDS], T cell deficiency syndromes, B cell deficiency syndromes, and chronic granulomatous disease).
21.Have signs or symptoms of infection with HIV, hepatitis B or hepatitis C.
22.Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening.
23.Have had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to screening.
24.Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB.
25.Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months prior to the first administration of study agent, during the study, or within 6 months after the last administration of study agent.
26.Have had a serious infection (eg, hepatitis, pneumonia, or pyelonephritis), have been hospitalized for an infection, or have been treated with parenteral antibiotics for an infection within 2 months prior to first administration of study agent. Less serious infections (eg, acute upper respiratory tract infection, simple urinary tract infection) need not be considered exclusionary at the discretion of the investigator.
Malignancy or increased potential for malignancy:
27.Presence or history of any malignancy within 5 years of screening (with exception of nonmelanoma skin cancer that has been treated with no evidence of recurrence).
28.Presence or history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic areas), or clinically significant hepatomegaly or splenomegaly.
Coexisting medical conditions or past medical history: see page 24 and 25 of the protocol (points 29 until 37).
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Part 1: Dose-ranging
· Change from baseline in the Mayo score at Week 6
Part 2: Dose-confirming
· Primary Endpoint: Clinical response at Week 6
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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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| 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) | 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 | 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 | Information not present in EudraCT |
| 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.8.3 |
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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 59 |
| 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
| |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 2 |
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