A Phase 2/3 Multicenter, Randomized, Placebo-controlled, Double blind Study to Evaluate the Safety and Efficacy of Golimumab Induction Therapy, Administered Subcutaneously, in Subjects with Moderately to Severely Active Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2006-003398-28-FR
• Date of registration: 23/07/2007
• Prospective Registration: Yes
• Primary sponsor: Centocor BV
• Public title: A Phase 2/3 Multicenter, Randomized, Placebo-controlled, Double blind Study to Evaluate the Safety and Efficacy of Golimumab Induction Therapy, Administered Subcutaneously, in Subjects with Moderately to Severely Active Ulcerative Colitis
• Scientific title: A Phase 2/3 Multicenter, Randomized, Placebo-controlled, Double blind Study to Evaluate the Safety and Efficacy of Golimumab Induction Therapy, Administered Subcutaneously, in Subjects with Moderately to Severely Active Ulcerative Colitis
• Date of first enrolment: 21/09/2007
• Target sample size: 676
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-003398-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Czech Republic, Denmark, France, Germany, Hungary, Latvia, Lithuania, Netherlands, Slovakia, Sweden

Key inclusion & exclusion criteria

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.

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:
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 vac

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ulcerative Colitis (UC)
MedDRA version: 9.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis

Intervention(s)

Product Name: Golimumab Liquid in prefilled syringe
Product Code: CNTO 148
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Golimumab
Current Sponsor code: CNTO148
Other descriptive name: Human Anti-TNF IgG1 Monoclonal Antibody; rTNV148B IgG; Human Anti-TNFalfa
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: To evaluate the efficacy of SC induction regimens of golimumab in inducing clinical remission.
To evaluate the efficacy of SC induction regimens of golimumab in inducing mucosal healing.
To evaluate the efficacy of SC 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, EudraCT 2006-003399-37).

Main Objective: Part 1: Dose-ranging

• To evaluate the dose response of SC golimumab induction regimens in subjects with moderately to severely active UC.
• To select SC 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 SC induction regimens of golimumab in inducing clinical response in subjects with moderately to severely active UC.
• To evaluate the safety of SC induction regimens of golimumab in subjects with moderately to severely active UC.

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

Secondary ID(s)

C0524T17

2006-003398-28-DE

Ethics review

Status: Approved
Approval date: 20/08/2007
Contact:

Results

• Results available: Yes
• Date Posted: 19/10/2016
• Date Completed: 06/10/2010
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-003398-28/results