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

• Register: EUCTR
• Last refreshed on: 12 November 2018
• Main ID: EUCTR2010-020992-21-SK
• Date of registration: 06/12/2011
• Prospective Registration: No
• 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, parallel groups, phase 2b/3 study to compare efficacy and safety of masitinib to methotrexate, 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: 26/10/2011
• 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: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Germany, Greece, India, Poland, Romania, Slovakia, Spain, Thailand, Tunisia, 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 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:ESR/first hour = 20 mm; 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:ACN = 2 x 109/L;White blood cells count = 4 x 109/L;Haemoglobin = 10 g/dL;PLT = 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. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test),who agrees to use two highly effective 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.Acceptable forms of contraception include:A documented placement of an intrauterine device (IUD) or intrauterine system (IUS) and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository);Documented tubal ligation (female sterilization). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository) should also be used;Double barrier method:Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;Any other contraceptive method with a documented failure rate of <1% per year;Abstinence
10. Male patients must use medically acceptable methods of contraception if your female partner is pregnant from the time of the first administration of the study drug until three months following administration of the last dose of study drug.Acceptable methods include:Condom;If you have undergone surgical sterilization (vasectomy with documentation of azoospermia) a condom should also be used. Male patients must use two highly effective 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. The acceptable methods of contraception are as follows: Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; Surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository);Your female partner uses oral contraceptives (combination oestrogen/pro
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 12 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: 20.0 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)

Primary end point(s): ?? Cumulative response on ACR50 (ie. response from week 8 to week 24)

Main Objective: Cumulative response on ACR50 (ie. response from week 8 to week 24)

Secondary Objective: ? Response assessment:
- Cumulative response on ACR20 (ie. response from W8 to W24),
- Cumulative response on ACR70 (ie. response from W8 to W24),
- Cumulative response on ACR90 (ie. response from W8 to W24)
- ACRn from W8 to W24
- Time to first response according to ACR20 and ACR50
- DAS28 from week 8 to week 24:
? DAS28 (disease activity score)
? DAS28 < 2.6 (complete remission),
? DAS28 = 3.2 (low disease activity),
- CRP and ESR level from week 8 to week 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 week 8 to week 24: pain, asthenia, general health
- Quality of life assessed of SF36 from W8 to W24
- Health assessment questionnaire (HAQ) score and from W8 to W24
- Hamilton score from W8 to W24
- Fatigue Impact scale from W8 to W24
? Safety assessments: Adverse events, vital signs, laboratory data.

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

Secondary Outcome(s)

Secondary end point(s): ? Response assessment:
- Cumulative response on ACR20 (ie. response from week 8 to week 24),
- Cumulative response on ACR70 (ie. response from week 8 to week 24),
- Cumulative response on ACR90 (ie. response from week 8 to week 24)
- ACRn from week 8 to week 24
- Time to first response according to ACR20 and ACR50
- DAS28 from week 8 to week 24:
? DAS28 (disease activity score)
? DAS28 < 2.6 (complete remission),
? DAS28 = 3.2 (low disease activity),
- CRP and ESR level from week 8 to week 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 week 8 to week 24:
? pain
? asthenia
? general health
- Quality of life assessed of SF36 from week 8 to week 24
- Health Assessment Questionnaire (HAQ) score and from week 8 to week 24
- Hamilton score from week 8 to week 24
- Fatigue Impact scale from week 8 to week 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