Comparison of efficacy of masitinib versus methotrexate in the treatment of rheumatoid arthritis

• Register: EUCTR
• Last refreshed on: 6 October 2015
• Main ID: EUCTR2010-020992-21-CZ
• Date of registration: 18/07/2011
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Comparison of efficacy of masitinib versus methotrexate in the treatment of rheumatoid arthritis
• Scientific title: A 24-week with possible extension, prospective, multicenter, randomised, double-blind, controlled, 3-parallel groups, phase 2b/3 study to compare efficacy and safety of masitinib at 3 and 4.5 mg/kg/day to methotrexate, with a randomisation 1:1:1, in treatment of patients with active rheumatoid arthritis with inadequate response to 1. methotrexate or to 2. any DMARD including at least one biologic drug if patients previously failed methotrexate or to 3. methotrexate in combination with any DMARD including biologic drugs - AB1010 in treatement of patients with active rheumatoide arthritis.
• Date of first enrolment: 12/10/2011
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020992-21
• 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: yes Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Czech Republic, Germany, Greece, India, Slovakia, Spain, Thailand, Turkey, United States

Contacts

• Name: Cécile VISSAC-SABATIER
• Affiliation: AB Science

• Name: Cécile VISSAC-SABATIER
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient with rheumatoid arthritis diagnosed according to American College of Rheumatology (ACR) criteria for at least 6 months.
2. Patient with ACR functional class I-III
3. Patient who have active RA consisting of
- = 6 swollen joints (over 66 swollen joints)
- = 6 tender joints (over 68 tender joints)
- and at least 2 out of 3 of the following:
• erythrocyte sedimentation rate (ESR/first hour) = 20 mm
• C-reactive protein (CRP) = 10 mg/L
• morning stiffness = 45 minutes at both screening and baseline.
4. Patient who failed (defined as active RA with stable dose during 3 months) methotrexate at a dose = 15 mg/week or any DMARD including biologics drugs if patients previously failed methotrexate at a dose = 15 mg/week or methotrexate at a dose = 15 mg/week in combination with any DMARD including biologics drugs (Biologic drugs being defined as any of the following therapies: anti-TNFa, Anti-CD20, Anti-IL1, Anti-IL6, CTLA4)
5. Patient with a disease onset at > 16 years of age
6. Patient with an adequate organ function:
• Absolute neutrophils count (ANC) = 2 x 109/L
• White blood cells count = 4 x 109/L
• Haemoglobin = 10 g/dL
• Platelets (PTL) = 100 x 109/L
• AST/ALT = 3 x ULN
• Bilirubin = 1.5 x ULN
• Creatinine clearance >60 mL/min
• Albuminemia > 1 x LLN
• Proteinuria < 30 mg/dL (1+) on the dipstick; in case of proteinuria = 1+ on the dipstick, 24 hours proteinuria < 1.5g/24 hours
7. Male or female patient aged 18 to 75 years, weight>50 kg, BMI between 18 and 35 kg/m²
8. No active infection (tuberculosis, HIV, hepatitis, ...)
9. Male or female patient of child bearing potential, must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake
10. Female patient of childbearing potential must have a negative pregnant test at screening and baseline
11. Patient able and willing to comply with study visits and procedures per protocol
12. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures being performed.
13. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion criteria:
1. Patient from whom the use of methotrexate is contraindicated as per its SPC (i.e. patient with severe renal or liver failure, patient with pre-existing blood dyscrasia, patient with alcohol abuse, patient with acute or chronic infection, patient with methotrexate intolerance, patient being treated with live attenuated vaccine)
2. Patient with documented fibromyalgia
3. Patient who have had a major surgery within 2 weeks prior to study entry
4. Patient with lactose intolerance
5. Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension, according to judgment of the investigator, or symptomatic hypertension
6. Patient with history of primary malignancy < 5 years; except treated basal cell skin cancer or cervical carcinoma in situ
7. Patient with a severe and/or uncontrolled medical condition
8. Pregnant or lactating woman
9. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.
10. Patient who were treated with methotrexate >20 mg cannot be included in the study
Previous treatments:
11. Administration of a DMARD (except methotrexate) within 4 weeks (or 5 half-lives, whichever is longer) prior to baseline except for leflunomide which requires a specific wash-out period of 2 weeks before baseline and infliximab which requires a wash-out period of 8 weeks.
12. Administration of more than one Non Steroidal Anti-Inflammatory Drug (NSAID) or change of dose of NSAID within 4 weeks of screening or NSAID use greater than the maximum recommended dose.
13. Administration of more than 10 mg/day of prednisone or equivalent or change in the dose of prednisone or equivalent, or having intra-articular corticosteroid injection or bolus intramuscular or intravenous treatment with corticosteroids (>20 mg prednisone or equivalent) within 4 weeks of screening.
14. Treatment with any investigational agent within 4 weeks of screening.



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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 16.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: not applicable
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: not applicable
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Methotrexate
Product Name: Methotrexate
Product Code: not applicable
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: METHOTREXATE
CAS Number: 59-05-2
Current Sponsor code: not applicable
Other descriptive name: not applicable
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2,5 mg-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Cumulative response on ACR20 (ie. response from week 8 to week 24)

Primary end point(s): ?• Cumulative response on ACR20 (ie. response from week 8 to week 24)

Main Objective: Cumulative response on ACR20 (ie. response from week 8 to week 24)

Secondary Objective: •Response assessment:
-Cumulative response on ACR50 (ie. response from w 8 to w 24),
-Cumulative response on ACR70 (ie. response from w 8 to w 24),
-Cumulative response on ACR90 (ie. response from w 8 to w 24)
-ACRn from w 8 to w 24
-Time to first response according to ACR20 and ACR50
-DAS28 from w 8 to w 24:
•DAS28 (disease activity score)
•DAS28 < 2.6 (complete remission),
•DAS28 < 3.2 (low disease activity),
-CRP and ESR level from w 8 to w 24
•CRP and ESR values
•Percentage of patients with an improvement of CRP and ESR >50%, between 25 and 50%, between 0 and 25% or no improvement
•Quality of life assessment:
-Visual assessment scale from w 8 to w 24:
? pain
? asthenia
? general health
-Quality of life assessed of SF36 from w 8 to w 24
-Health Assessment Questionnaire (HAQ) score and from w 8 to w 24
-Hamilton score from w 8 to w 24
-Fatigue Impact scale from w 8 to w 24
•Safety assessments: Adverse events, vital signs, laboratory data

Secondary Outcome(s)

Secondary end point(s): Response assessment:
-Cumulative response on ACR50 (ie. response from w 8 to w 24),
-Cumulative response on ACR70 (ie. response from w 8 to w 24),
-Cumulative response on ACR90 (ie. response from w 8 to w 24)
-ACRn from w 8 to w 24
-Time to first response according to ACR20 and ACR50
-DAS28 from w 8 to w 24:
•DAS28 (disease activity score)
•DAS28 < 2.6 (complete remission),
•DAS28 < 3.2 (low disease activity),
-CRP and ESR level from w 8 to w 24
•CRP and ESR values
•Percentage of patients with an improvement of CRP and ESR >50%, between 25 and 50%, between 0 and 25% or no improvement
•Quality of life assessment:
-Visual assessment scale from w 8 to w 24:
? pain
? asthenia
? general health
-Quality of life assessed of SF36 from w 8 to w 24
-Health Assessment Questionnaire (HAQ) score and from w 8 to w 24
-Hamilton score from w 8 to w 24
-Fatigue Impact scale from w 8 to w 24
•Safety assessments: Adverse events, vital signs, laboratory data

Timepoint(s) of evaluation of this end point: response from week 8 to week 24

Secondary ID(s)

2010-020992-21-DE

AB06012

Source(s) of Monetary Support

AB Science