A Golimumab Phase 3b, Multicenter, Switch Assessment of Subcutaneous and Intravenous Efficacy in Rheumatoid Arthritis Patients Who Have Inadequate Disease Control Despite Treatment with Etanercept (ENBREL®) or Adalimumab (HUMIRA®)

• Register: EUCTR
• Last refreshed on: 24 February 2014
• Main ID: EUCTR2009-010582-23-DE
• Date of registration: 22/09/2009
• Prospective Registration: Yes
• Primary sponsor: Janssen Biologics B.V.
• Public title: A Golimumab Phase 3b, Multicenter, Switch Assessment of Subcutaneous and Intravenous Efficacy in Rheumatoid Arthritis Patients Who Have Inadequate Disease Control Despite Treatment with Etanercept (ENBREL®) or Adalimumab (HUMIRA®)
• Scientific title: A Golimumab Phase 3b, Multicenter, Switch Assessment of Subcutaneous and Intravenous Efficacy in Rheumatoid Arthritis Patients Who Have Inadequate Disease Control Despite Treatment with Etanercept (ENBREL®) or Adalimumab (HUMIRA®)
• Date of first enrolment: 04/01/2010
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010582-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: First part open, second part double blind If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Belgium, Germany, Greece, Italy, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Are women or men 18 years of age or older.
2. Have inadequate RA disease control prior to the first administration of study agent despite treatment with etanercept or adalimumab in combination with MTX for a minimum of 3 months prior to the first screening visit:
- Etanercept at the approved dose of 50 mg SC once weekly or 25 mg SC injections twice weekly in combination with MTX at Week 0, or
- Adalimumab at the approved dose of 40 mg SC injection every 2 weeks in combination with MTX at Week 0
The last dose of etanercept must be administered no less than 7 days before the first golimumab injection at Week 0, and the last dose of adalimumab must be administered no less than 14 days before the first golimumab injection at Week 0.
3. Must have received a stable dose of MTX = 7.5 mg/week to = 25 mg/week for at least 4 consecutive weeks prior to the first screening visit and must plan to maintain that dose throughout the study as described in Section 7.3.1.
4. If using NSAIDs for RA, must be on a stable dose for at least 4 consecutive weeks before the first screening visit.
5. If using oral corticosteroids, must be on a stable dose equivalent to = 10 mg of prednisone/day for at least 4 consecutive weeks before the first screening visit. If currently not using corticosteroids, the patient must have not received oral corticosteroids for at least 4 weeks before the first screening visit.
6. If using hydroxychloroquine and/or sulfasalazine, must have received a stable dose for at least 4 consecutive weeks before the first screening visit and must plan to maintain that dose throughout the study.
7. Women of childbearing potential or men capable of fathering children must be using adequate birth control measures during the study and for 6 months after receiving the last administration of study agent. Female patients must test negative for pregnancy.
8. Are considered eligible according to the following TB screening criteria:
- Have no history of latent or active TB prior to screening. An exception is made for patients with a history of latent TB and documentation of having completed appropriate treatment for latent TB within 3 years prior to the first administration of study agent.
- Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
- Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment as if having latent TB prior to or simultaneously with the first administration of study agent.
- Within 6 weeks prior to the first administration of study agent, either have a negative QuantiFERON-TB Gold test result, or have a newly identified positive QuantiFERON-TB Gold test result in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent.
- In the event of 2 indeterminate QuantiFERON-TB Gold in-tube test results, the patient will be treated as if having latent TB prior to or simultaneously with the first administration of study agent.
- Have a chest radiograph, demonstrating no evidence of current active TB or old inactive TB, and taken within 12 months of the study or at the screening visit if the patient has received either etanercept or adalimumab continuously throughout this period.
9. Have screening
Exclusion criteria:
1. Have a history of latent or active granulomatous infection, including histoplasmosis, or coccidioidomycosis, prior to the first screening visit or during the Screening Period. Pulmonary calcifications in isolation are not considered indicative of latent histoplasmosis. Refer to inclusion criteria for information regarding eligibility with a history of latent TB.
2. Have had a BCG vaccination within 12 months of screening.
3. 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, histoplasmosis, or coccidioidomycosis.
4. Have had a nontuberculous mycobacterial infection or opportunistic infection within 6 months prior to the first screening visit or during the Screening Period.
5. Have inflammatory diseases other than RA which might confound the evaluation of the benefit of golimumab therapy.
6. Have been treated with DMARDs/systemic immunosuppressive agents during the 4 weeks prior to the first screening visit. Patients may have received MTX, sulfasalazine, or hydroxychloroquine.
7. Have received IA, IM, or IV corticosteroids during the 4 weeks prior to the first screening visit.
8. Have demonstrated a discernible improvement in disease activity as demonstrated by an ESR-based DAS28 response and as defined by the EULAR criteria between screening and prior to the first golimumab injection at Week 0.
9. Have a known hypersensitivity to components of golimumab.
10. Have had a clinically serious adverse reaction to a biologic anti-TNFa agent.
11. Have received infliximab, golimumab, or certolizumab prior to the first administration of the study agent.
12. Have received natalizumab, rituximab, tocilizumab, abatacept, or efalizumab prior to the first administration of the study agent.
13. Have received anakinra during the 4 weeks prior to the first screening visit.
14. Have received alefacept within the 3 months prior to the first screening visit.
15. Have used cytotoxic agents, including chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents.
16. Have received any investigational anti-TNFa agent including but not limited to lenercept or onercept.
17. Have been treated with the investigational agents ocrelizumab, ofatumumab, or a janus kinase 3 inhibitor at any time, or any other investigational drug within 5 half-lives of that drug prior to the first administration of study agent.
18. Are pregnant, nursing, or planning a pregnancy or fathering a child within 6 months after receiving the last administration of the study agent.
19. 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 trial, or within 6 months after the last administration of study agent.
20. Have a history of an infected joint prosthesis, or have received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced.
21. Have had a serious infection, have been hospitalized for an infection, or have been treated with IV antibiotics for an infection within 2 months prior to the first administration of study agent. Less serious infections need not be considered exclusionary at the discretion of the investigator.
22. Have a history of, or ongoing, chronic or recurrent infectious disease.
23. Are known to be infected with HIV, hepatitis B, or hepatitis C.
24. Have a histor

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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 12.0 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: Golimumab Final Vialed Product (FVP)
Product Code: CNTO 148
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Golimumab
Current Sponsor code: CNTO 148
Other descriptive name: Human anti TNF-alpha monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: Golimumab liquid in prefilled pen
Product Code: CNTO 148
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Golimumab
Current Sponsor code: CNTO 148
Other descriptive name: Human anti TNF-alpha monoclonal antibody
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)

Main Objective: The primary objective of this study is to evaluate the efficacy of golimumab + MTX in reducing signs and symptoms of RA (as assessed by the American College of Rheumatology [ACR] 20) at Week 14 in patients with inadequate disease control despite treatment with etanercept + MTX or adalimumab + MTX.

Primary end point(s): The primary efficacy endpoint is the proportion of patients who achieve an ACR 20 response at Week 14.

Secondary Objective: The 3 major secondary objectives of this study are to assess the following:
• The onset of response to golimumab 50 mg SC every 4 weeks + MTX as defined by the proportion of patients who achieve an ACR 20 response within 2 weeks of initiating therapy
• The persistence of response to golimumab 50 mg SC every 4 weeks + MTX as defined by the proportion of patients who achieve a DAS28 “good” response by Week 16 and maintain this response through Week 52
• The efficacy of golimumab 2 mg/kg intravenous (IV) therapy + MTX defined by the relative proportions of randomized patients in the golimumab IV group (with a loading dose) and the golimumab SC groups who achieve an ACR 20 response at Week 52 relative to Week 16

To further evaluate the long-term efficacy and safety of golumimab treatment, a voluntary, open-label, 24-week study extension is held during weeks 53 to 88, consisting of 3 additional visits and a telephone follow-up in week 88.

Secondary ID(s)

CNTO148ART3002