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

• Register: EUCTR
• Last refreshed on: 28 September 2015
• Main ID: EUCTR2010-020992-21-DE
• Date of registration: 08/07/2011
• 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: 25/03/2014
• 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

Countries of recruitment

Argentina, Bosnia and Herzegovina, Czech Republic, Germany, Greece, India, Mexico, Monaco, Morocco, Philippines, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Taiwan, Thailand, Tunisia, Ukraine, United States

Contacts

• Name: Iva Nesic
• Affiliation: AB Science

• Name: Iva Nesic
• 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/progesteron
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 preexisting
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.



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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 17.1 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-
Pharmaceutical form of the placebo: Film-coated 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

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: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

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

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

Main Objective: Cumulative response on ACR50 (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)

AB06012

Source(s) of Monetary Support

AB Science