Safety and efficacy of combination treatment with rituximab and leflunomide in patients with active rheumatoid arthritis - Rituximab and Leflunomide in RA

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2005-004582-41-GB
• Date of registration: 27/01/2006
• Prospective Registration: Yes
• Primary sponsor: University of Leeds
• Public title: Safety and efficacy of combination treatment with rituximab and leflunomide in patients with active rheumatoid arthritis - Rituximab and Leflunomide in RA
• Scientific title: Safety and efficacy of combination treatment with rituximab and leflunomide in patients with active rheumatoid arthritis - Rituximab and Leflunomide in RA
• Date of first enrolment: 24/03/2006
• Target sample size: 15
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004582-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
•Male and female patients aged between 18 and 80 years.
•Diagnosis of rheumatoid arthritis (1987 revised ACR criteria) confirmed at least 6 months prior screening
•Persisting RA activity despite treatment with leflunomide for at least 16 weeks with 20 mg/day or 10 mg/day. Dose stable for four weeks prior to baseline
•Subjects with active RA at baseline defined as: DAS 28 >5.1
•Rheumatoid factor positive

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 inflammatory joint disease of different origin, mixed connective tissue disease, Reiter’s syndrome, psoriatic arthritis, systemic lupus erythematous, or any arthritis with onset prior to 16 years of age.
2.Suspicion of diagnosis of tuberculosis (positive tuberculosis test (>5mm induration if previous BCG or >10mm if no previous BCG) or abnormal chest x-ray).
3.Patients with concomitant medical condition which would in the investigator’s opinion compromise the patient’s ability to tolerate, absorb, metabolise or excrete the study medication.
4.Patients with serious infections within 3 month of enrollment (screening) or persistent infections.
5.Patients at significant risk of infection (e.g. leg ulceration, indwelling urinary catheter, septic joint within 1 year (or ever if prosthetic joint still in situ)).
6.Patients with malignancy (other than excised basal cell carcinoma) within the last 5 years before study entry (screening).
7.Patients with history of Felty’s syndrome, uncontrolled diabetes, uncontrolled hypertension, unstable ischaemic heart disease, active bowel disease, active peptic ulcer disease, recent stroke (within three month before study entry (screening)), or other condition which, in the opinion of the investigator, would put the patient at risk to participate in the study.
8.Known positive serology for hepatitis B or C, or HIV
9.Patients with acute major trauma.
10.Patients with body weight < 45 kg.
11.Clinically relevant cardiovascular, hepatic, neurologic (such as multiple sclerosis, optic neuritis etc.), endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult.
12.Impaired hepatic function, as shown by ALT or ALP more than or equal to 1,5 times the laboratory upper limit of normal or Serum albumin < 30 g/l.
13.Patients with significantly impaired bone marrow function as for example significant anaemia, leukopenia, neutropenia or thrombocytopenia.


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

Health Condition(s) or Problem(s) studied

Active Rheumatoid Arthritis

Intervention(s)

Trade Name: Mabthera
Product Name: Mabthera
Product Code: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion

Trade Name: Arava
Product Name: Arava
Product Code: Leflunomide
Pharmaceutical Form: Film-coated tablet

Trade Name: Solu-Medrone 2 Gram
Product Name: Solu-Medrone 2mg
Product Code: Methylprednisolone
Pharmaceutical Form: Powder for injection*

Primary Outcome(s)

Primary end point(s): Efficacy will be defined by Disease Activity Score (DAS28)
The DAS28 calculation is based on the evaluation of four variables:
-28 tender joints
-28 swollen joins
-Erythrocyte Sedimentation Rate (ESR)
-Patient’s general health status, as assessed by a 100 mm visual analogue scale (VAS)
Investigators global assessment (VAS )
Patient pain assessment (VAS)
Rheumatoid Arthritis Quality of Life scale (RAQoL)
Health Assessment Questionnaire (HAQ)
CRP
Rheumatoid Factor titre
Radiological assessments (plain X-ray, HRUS, MRI)
Early morning stiffness

Main Objective: Primary objective is to assess safety of rituximab combined with leflunomide. Safety will be evaluated by the frequency of Adverse Events and the outcome of laboratory blood monitoring.

Secondary Objective: Secondary objective is to assess efficacy of rituximab combined with leflunomide in active RA patients

Secondary ID(s)

RTX/LFU rheumatoid arthritis.

Ethics review

Status: Approved
Approval date:
Contact: