A double-blind, randomized, placebo controlled, dose escalation, multi-center phase I/II trial of HuMax-CD20, a fully human monoclonal anti-CD20 antibody, in patients with active rheumatoid arthritis who have previously failed one or more disease modifying anti-rheumatic drugs. - HuMax-CD20 in Active Rheumatoid Arthritis, Phase I/II

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2004-003771-37-HU
• Date of registration: 03/11/2005
• Prospective Registration: Yes
• Primary sponsor: Genmab A/S
• Public title: A double-blind, randomized, placebo controlled, dose escalation, multi-center phase I/II trial of HuMax-CD20, a fully human monoclonal anti-CD20 antibody, in patients with active rheumatoid arthritis who have previously failed one or more disease modifying anti-rheumatic drugs. - HuMax-CD20 in Active Rheumatoid Arthritis, Phase I/II
• Scientific title: A double-blind, randomized, placebo controlled, dose escalation, multi-center phase I/II trial of HuMax-CD20, a fully human monoclonal anti-CD20 antibody, in patients with active rheumatoid arthritis who have previously failed one or more disease modifying anti-rheumatic drugs. - HuMax-CD20 in Active Rheumatoid Arthritis, Phase I/II
• Date of first enrolment: 03/03/2006
• Target sample size: 230
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-003771-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Dose escalation If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Hungary

Key inclusion & exclusion criteria

Inclusion criteria:
1) Males and females = 18 years
2) A diagnosis of rheumatoid arthritis according to the American College of Rheumatology (ACR) of at least six months duration
3) Active disease at the time of screening as defined by :
- Six or more swollen joins (of 28 joints)
and
- Six or more tender joints (of 28 joints)
and
- Erythrocyte Sedimentation Rate (ESR) = 22 mm/h (using Becton Dickinson Seditainer) and/or C-Reactive Protein (CRP) = 10 mg/L (1 mg/dL)
4) RA functional class I, II, or III
5) Treatment failure to one or more DMARDs.
- Treatment failure is defined as either intolerance at any time or insufficient efficacy after a minimum of 12 weeks of DMARD treatment.
- DMARDs include, among others, methotrexate, hydroxychloroquine, chloroquine, gold preparations, azathioprine, D-penicillamine, sulfasalazine, minocycline, leflunomide, and cyclosporine A.
6) Applicable only to patients on methotrexate therapy at time of screening: Treatment with methotrexate for at least 12 weeks prior to planned start of trial treatment (Visit 2), with possible interruption of treatment of maximum two weeks in total, in the period 5-12 weeks from Visit 2.
7) Applicable only to patients on methotrexate therapy at time of screening: Treatment with a stable dose of methotrexate (7.5 – 25 mg/week, p.o., i.m., and/or s.c.) for at least four weeks prior to planned start of trial treatment (Visit 2)

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) Use of DMARDs (other than methotrexate, if patient is on methotrexate treatment at time of screening): = 4 weeks prior to planned start of trial treatment (Visit 2).If patient is not on methotrexate treatment at time of screening: Methotrexate = 4 weeks prior to planned start of trial treatment (Visit 2). Specifically for leflunomide treatment: Use of leflunomide =12 weeks prior to planned start of trial treatment (visit 2) unless the patient has completed peroral cholestyramine treatment for washout, according to locally accepted clinical practices.
2) Exposure to other biological products (e.g. etanercept, infliximab, adalimumab, and kineret) within 4 weeks prior to planned start of trial treament (Visit 2), and/or exposure to anti-CD20 antibodies within two years before screening for this trial
3) Any use of cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents within five years before screening for this trial
4) Within four weeks prior to planned start of trial treatment (Visit 2):
- Treatment with oral corticosteroids ( > 10 mg prednisolone per day or equivalent)
- Start of oral corticosteroid treatment
- Change in any ongoing oral corticosteroid dose
5) Use of intra-articular, i.m. or i.v. corticosteroids (including i.m. adrenocorticotrophe hormone) within four weeks prior to planned start of trial treatment (Visit 2)
6) Active autoimmune disease (other than RA and RA-associated secondary diseases) requiring immunosuppressive therapy
7) Diagnosis of fibromyalgia or other chronic pain syndrome requiring daily narcotic treatment
8) Past or current malignancy, except for
- Resected cervical carcinoma Stage 1B or less
- Resected non-invasive basal cell and squamous cell skin carcinoma
- Malignant melanoma with a complete response of a duration of > 10 years
- Other cancer diagnoses with a complete response of a duration of > 5 years
9) Chronic or current infectious disease such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, sinusitis, and tuberculosis
10) History of infected joint prosthesis within five years before Visit 1 and infected native joints within one year before Visit 1
11) Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities
12) Significant concurrent uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
13) History of significant cerebrovascular disease
14) Screening laboratory values:
- Hemoglobin < 6.2 mmol/L (9.9 g/dL)
- Neutrophils < 2 x 109/ L
- Platelets < 100 x 109/ L
- S-ALAT > 1.5 times the upper limit of normal
- S-ALP > two times the upper limit of normal
- S-creatinine > 133 µmol/L (1.5 mg/dL)
15) Known or suspected positive serology for HIV
16) Positive serology for hepatitis B or C
17) Patients previously screened for this trial, unless reason for previous screen failure was failure to fulfill inclusion criterion no. 3
18) Current or previous (within four weeks of screening) participation in any other clinical trial
19) Patients known or suspected to be unable to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
20) Breast feeding women or women with a positive

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

Health Condition(s) or Problem(s) studied

Active Rheumatoid Arthritis
MedDRA version: 7.0 Level: LLT Classification code 10039073

Intervention(s)

Product Name: HuMax-CD20
Product Code: HuMax-CD20
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: N/A
CAS Number: 679818-59-8
Current Sponsor code: HuMax-CD20
Other descriptive name: Human monoclonal antibody directed against CD20 on B-cells
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: Part A and B:
To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis by measuring the degree and duration of B-cell depletion

To determine the pharmacokinetic profile of HuMax-CD20 in patients with active rheumatoid arthritis

To determine host immune response, Human Anti Human Antibodies (HAHA), against HuMax-CD20

Part B:
To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis.

Main Objective: Part A: To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis.
Part B: To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 12 to 24 weeks after initiation of treatment.

Primary end point(s): Part A: Adverse Events.
Part B: ACR20

Secondary ID(s)

Hx-CD20-403