A double-blind, randomized, placebo controlled, parallel group, multi-center, phase III trial of ofatumumab investigating clinical efficacy in adult patients with active rheumatoid arthritis who had an inadequate response to TNF-a antagonist therapy - Investigating efficacy of ofatumumab in RA patients with inadequate response to TNF-a antagonist

• Register: EUCTR
• Last refreshed on: 22 April 2013
• Main ID: EUCTR2007-002951-18-DK
• Date of registration: 23/04/2008
• Prospective Registration: Yes
• Primary sponsor: Genmab A/S
• Public title: A double-blind, randomized, placebo controlled, parallel group, multi-center, phase III trial of ofatumumab investigating clinical efficacy in adult patients with active rheumatoid arthritis who had an inadequate response to TNF-a antagonist therapy - Investigating efficacy of ofatumumab in RA patients with inadequate response to TNF-a antagonist
• Scientific title: A double-blind, randomized, placebo controlled, parallel group, multi-center, phase III trial of ofatumumab investigating clinical efficacy in adult patients with active rheumatoid arthritis who had an inadequate response to TNF-a antagonist therapy - Investigating efficacy of ofatumumab in RA patients with inadequate response to TNF-a antagonist
• Date of first enrolment: 03/06/2008
• Target sample size: 236
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002951-18
• 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: yes Other trial design description: Initial double blind period: randomised, double-blind, parallel group. Extension period: open label If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1) Age = 18 years
2) A diagnosis of rheumatoid arthritis according to the American College of Rheumatology (ACR1987 classification) of at least six months’ duration from diagnosis at screening
3) Active disease at the time of screening as defined by:
= 8 swollen joints (of 66 joints assessed)
and
= 8 tender joints (of 68 joints assessed)
and
C-Reactive Protein (CRP) = 1.0 mg/dL or Erythrocyte Sedimentation Rate (ESR) = 22 mm/hour
and
DAS28=3.2 (based on ESR)
Note: The swollen and tender joints must be reassessed at baseline (Visit 2) to ensure these eligibility criteria are fulfilled prior to randomization. Where possible joint count reassessment must be performed at the baseline visit (Visit 2); if this is not possible it can be performed = 3 days prior to Visit 2.
4) RA functional class I, II or III
5) Inadequate response to previous or current TNF-a antagonist treatment after infliximab therapy (=3 mg/kg; at least 4 infusions), or adalimumab therapy (40 mg every other week for =3 months), or etanercept therapy (25 mg twice weekly or 50 mg once a week for =3 months) defined as:
Inadequate efficacy according to the investigator’s judgment
and/or
Intolerance defined as one or more side effects following at least one administration of one of the TNF-a antagonists at the dose listed above that reasonably results in the discontinuation of treatment with the TNF-a antagonist treatment
6) Treatment with methotrexate (MTX), 7.5-25 mg/week, for at least 12 weeks and at a stable dose for at least 4 weeks prior to Visit 2. Doses of MTX as low as 7.5 mg per week are permitted for patients who can not tolerate higher doses
7) Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity including wash-out of other drug products is carried out
France: In France, a patient will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

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) Patients with a history of a rheumatic autoimmune disease other than RA (except secondary Sjögren's syndrome), significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome)
2) Previous exposure to biologic cell depleting anti-rheumatic therapies, including investigational compounds (e.g. anti-CD11a, anti-CD19, anti-CD20, anti-CD22, anti-BLyS/BAFF, anti-CD3, anti-CD4, anti-CD5, CAMPATH)
3) Exposure to etanercept = 4 weeks, infliximab or adalimumab = 8 weeks, or abatacept = 12 weeks prior to Visit 2
4) Received any of the following treatments within 4 weeks prior to Visit 2:
- Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues, monoclonal antibodies)
- Glucocorticoid unless given in doses equivalent to = 10 mg of prednisolone /day
- Intra-articular, i.m. or i.v. corticosteorids
- Live/attenuated vaccinations
- Cyclosporine
- Azathioprine
- Penicillamine
5) Exposure to sulfasalazine within 6 weeks prior to Visit 2
6) Exposure to leflunomide within 12 weeks prior to Visit 2 unless the patient has completed peroral cholestyramine treatment for washout according to locally accepted clinical practices
7) Exposure to gold therapy or hydroxychloroquine = 12 weeks prior to Visit 2
8) Exposure to i.v. immunogammaglobulins = 24 weeks prior to Visit 2
9) Past or current malignant melanoma
10) Past or current malignancy, except for:
- Cervical carcinoma Stage 1B or less
- Non-invasive basal cell and squamous cell skin carcinoma
- Other cancer with complete response duration of > 5 years
11) Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis B and C
12) Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from screening, congestive heart failure, known QT abnormalities, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities
13) Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease, or evidence of demyelinating disease
14) History of significant cerebrovascular disease
15) Known HIV positive
16) Screening laboratory values (according to central laboratory):
- Hemoglobin < 5.6 mmol/L (9.0 g/dL)
- Neutrophils < 2 x 109/ L
- Platelets < 100 x 109/ L
- Serum IgG < lower limit of normal
- S-ALAT > 3.0 times the upper limit of normal
- S-AST > 1.5 times the upper limit of normal
- S-ALP > 2 times the upper limit of normal
- S-creatinine > 133 µmol/L (1.5 mg/dL)
17) Positive serology for hepatitis B (HB) defined as:
- Positive test for HBsAg and/or
- Positive test for anti-HBc and anti-HBs
Patients with documented vaccination against Hepatitis B (primary and secondary immunization and booster) will be considered negative
18) Positive plasma / white cell JC Virus (JCV) PCR (either compartment)
19) Known hypersensitivity to components of the investigational medicinal product
20) Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to screening
21) Current participation in any other interventional clinical study
22) Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism

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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: Ofatumumab
Product Code: HuMax-CD20
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ofatumumab
CAS Number: 679 818-59-8
Current Sponsor code: HuMax-CD20
Concentration unit: mg/ml milligram(s)/millilitre
Concentration number: 20-
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To demonstrate efficacy of ofatumumab in reducing clinical signs and symptoms in adult RA patients after a single course of ofatumumab

Secondary Objective: 1) To evaluate long-term efficacy of repeated courses of ofatumumab
2) To evaluate ofatumumab with respect to impact on patient reported outcomes after single and repeated courses of ofatumumab
3) To evaluate the risk of host immune response against ofatumumab after single and repeated courses of ofatumumab
4) To evaluate the safety of ofatumumab after single and repeated courses of ofatumumab

Primary end point(s): ACR20 at 24 weeks

Secondary ID(s)

GEN411/OFA110634

2007-002951-18-NL