A CONTROLLED RANDOMIZED DOUBLE-BLIND MULTICENTER STUDY COMPARING TWO THERAPY STRATEGIES IN DMARD-NAIVE EARLY RHEUMATOID ARTHRITIS PATIENTS OVER 48 WEEKS: INDUCTION THERAPY WITH ADALIMUMAB AND METHOTREXATE OVER 24 WEEKS FOLLOWED BY METHOTREXATE MONOTHERAPY UP TO WEEK 48 VS. METHOTREXATE MONOTHERAPY - HIT HARD

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-003146-41-DE
• Date of registration: 23/11/2006
• Prospective Registration: Yes
• Primary sponsor: Charité-Universitätsmedizin Berlin; Department of Rheumatology and Clinical Immunology
• Public title: A CONTROLLED RANDOMIZED DOUBLE-BLIND MULTICENTER STUDY COMPARING TWO THERAPY STRATEGIES IN DMARD-NAIVE EARLY RHEUMATOID ARTHRITIS PATIENTS OVER 48 WEEKS: INDUCTION THERAPY WITH ADALIMUMAB AND METHOTREXATE OVER 24 WEEKS FOLLOWED BY METHOTREXATE MONOTHERAPY UP TO WEEK 48 VS. METHOTREXATE MONOTHERAPY - HIT HARD
• Scientific title: A CONTROLLED RANDOMIZED DOUBLE-BLIND MULTICENTER STUDY COMPARING TWO THERAPY STRATEGIES IN DMARD-NAIVE EARLY RHEUMATOID ARTHRITIS PATIENTS OVER 48 WEEKS: INDUCTION THERAPY WITH ADALIMUMAB AND METHOTREXATE OVER 24 WEEKS FOLLOWED BY METHOTREXATE MONOTHERAPY UP TO WEEK 48 VS. METHOTREXATE MONOTHERAPY - HIT HARD
• Date of first enrolment: 08/03/2007
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-003146-41
• 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: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
Each patient must meet all of the following inclusion criteria to be enrolled into this study:
- Patients with definite RA referring to the ACR Classification Criteria of 1987 up to 1 year after first RA symptoms
- Age 18 to 70 years
- Has active disease at the time of randomization as indicated by 6 from 68 tender and 6 from 66 swollen joints and at least one of the following two criteria: Westergren erythrocyte sedimentation rate (ESR) ¸ 28 mm/hour od C-reactive protein (CRP) levels > 1.0 mg/dl.
- Has morning stiffness > 30 min.
- No current or prior therapy with DMARDs or biologics.
- NSAIDs and corticosteroids treatment has to be stable 2 weeks prior to
screening and during the trial with maximal · 10 mg/d prednisoloneequivalent.
- Is capable of understanding and signing an informed consent form
- Is able and willing to self-inject study drug or have a designee who can do so
- Is able and willing to take oral medication
- Is able to store injectable test article at 2± C to 8± C
- Sexually active women participating in the study must use a medically acceptable form of contraception for women. This includes oral contraception, injectable or implantable methods, intrauterine devices, or properly used barrier contraception.
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:
Patients meeting any following exclusion criteria are not to be enrolled in
this study:
- Has significant concurrent medical diseases including cancer or a history of cancer (other than resected cutaneous basal and squamous cell carcinoma, in situ cervical cancer) in the last 5 years
- Has uncompensated congestive heart failure, myocardial infarction within 12 months, unstable angina pectoris, uncontrolled hypertension, severe pulmonary disease, or history of human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, other rheumatologic diseases than RA, or central nervous systems demyelinating events suggestive or multiple sclerosis
- Received anti-CD4, diphtheria interleukin-2 fusion protein, antiinterleukin- 6, rituximab or other immunsuppressive biologic before screening, and treatment with such agents if there are persistent signs of immunosuppression (with a subsequent abnormal absolute T-cell count) at screening count.
- Received any live (attenuated) vaccines within 4 weeks of screening visit.
- Received intra-articular corticosteroid injection within 4 weeks of screening.
- Received bolus intramuscular/intravenous treatment with corticosteroids (>10 mg prednisone or equivalent) within 4 weeks of screening visit
- Is taking > 10 mg/d prednisone or equivalent
- Has a history of confirmed blood dyscrasias
- Has a significant active infection or any underlying diseases that could predispose subjects to infections (e.g. history of recurring infections, leg ulcers, advanced or poorly controlled diabetes)
- Has active infection with Hep A, B, C virus, tuberculosis, chronic infections, latent tuberculosis (has to be excluded by Chest x-ray and PPD-Test according to Mendel-Mantoux); In case of latent tuberculosis isoniazid 300 mg for 10 months, starting 1 month prior to treatment is obligatory
- Has renal disease (creatine level > 175 ¹mol/L) or a history of known liver cirrhosis, fibrosis
- Has an abnormal liver function (AST, GGT, ALT ¸ 2 x upper limit of normal)
- Has a history of psychiatric disease that would interfere with the ability to comply with the study protocol.
- Is pregnant or breast-feeding


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

Health Condition(s) or Problem(s) studied

Musculoskeletal disorders
MedDRA version: 8.1 Level: LLT Classification code 10048592 Term: Musculoskeletal disorder

Intervention(s)

Trade Name: Humira
Product Name: HUMIRA
Pharmaceutical Form: Injection*
INN or Proposed INN: Adalimumab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Injection*
Route of administration of the placebo: Subcutaneous use

Trade Name: Metex
Product Name: Metex
Pharmaceutical Form: Injection*

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint will be the DAS 28 score at week 48.

Main Objective: To compare the efficacy of an induction therapy over 24 weeks with subsequent
MTX therapy to MTX alone over 48 weeks in subjects with active early RA.
Efficacy is primary measured with the DAS 28 at week 48.

Secondary Objective: The secondary objectives of this study are:
- To evaluate DAS 28 at week 24,
- The partial-remission (DAS 28 < 2,6) at week 24 and 48,
- The duration of clinical remission during the trial,
- The variables of the WHO/ILAR core set for clinical trials (DAS 28, HAQ),
- To evaluate ACR 20,ACR 50, ACR 70 from baseline to week 24,
- To evaluate ACR 20,ACR 50, ACR 70 from baseline to week 48,
- The change in ACR 20,ACR 50, ACR 70 response between from week 24 to week 48,
- The radiographic change (x - ray of hands and feet in 2 dimensions) from baseline to week 48 by central assessment by the modifyed Sharp-Score and Ratingen Score,
- descriptive analysis of change Glucocorticoid, NSAIDs/Coxib dosage,
- Report on adverse events and serious adverse events (referring to ICH GCP/CPMP ICH E2).

Secondary ID(s)

50021031-2

36745608