A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of R935788 in Patients with Rheumatoid Arthritis Who Have Failed at Least One Biologic

• Register: EUCTR
• Last refreshed on: 8 August 2022
• Main ID: EUCTR2008-000743-34-FR
• Date of registration: 17/04/2008
• Prospective Registration: Yes
• Primary sponsor: Rigel Pharmaceuticals, Inc.
• Public title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of R935788 in Patients with Rheumatoid Arthritis Who Have Failed at Least One Biologic
• Scientific title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of R935788 in Patients with Rheumatoid Arthritis Who Have Failed at Least One Biologic
• Date of first enrolment: 21/07/2008
• Target sample size: 195
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000743-34
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Germany, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
1) Patients must give written informed consent by signing an IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study.
2) Males and females, 18 years of age or older, with active RA for at least 12 months prior to Day 1 dosing (functional class I–III, e.g., not bed or wheelchair-bound)
Active RA is defined as the presence of (a) = 6 swollen joints (28 joint count); AND (b) = 6 tender joints (28 joint count); AND at least one of the following (c) ESR >28 mm/hr or CRP >ULN for the central reference laboratory.
3) Are currently receiving or previously had received a biologic therapy with an inhibitor of TNF, rituximab, abatacept, or anakinra at an approved labeled dose for =3 months prior to Day 1 dosing and are designated as biologic therapy failures for lack of efficacy, safety, or tolerability.
4) Patients may receive stable doses of methotrexate (MTX), azathioprine (not in combination with MTX), leflunomide (not in combination with MTX), sulfasalazine, chloroquine, hydroxychloroquine, gold, NSAIDs (including COX2 inhibitors), minocycline, or doxycycline. The dose must have been stable for at least 30 days prior to Day 1 dosing and must not be changed during the washout, screening and treatment periods, unless dictated by tolerability requirements. Patients who are taking MTX must have been receiving weekly MTX doses (7.5–25 mg/week) for a minimum of 3 months prior to Day 1 dosing and must be receiving a stable MTX dose, with no change in route, for the previous 6 weeks prior to Day 1 dosing. Patients who are receiving MTX must also be receiving folic or folinic acid supplementation at a stable dose for at least 6 weeks prior to Day 1 dosing.
5) Females of childbearing potential must be fully informed of the potential for R788 to adversely affect the fetus and, if sexually active, must agree to use a well established method of birth control during the study (oral contraceptive, mechanical barrier, long acting hormonal agent). These patients must not be lactating and must have a negative urine pregnancy test at the time of randomization and at each laboratory determination.
6) The patient must otherwise be in good health as determined by the Investigator on the basis of medical history, physical examination, and laboratory screening tests during the screening period. See exclusion criteria for specific exclusions.
7) In the Investigator’s opinion, the patient has the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol.
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) The patient has a history of, or a concurrent, clinically significant illness, medical condition (other than arthritis) or laboratory abnormality that, in the Investigator’s opinion, could affect the conduct of the study. Specifically, excluded are patients with the following:
a) uncontrolled or poorly controlled hypertension;
b) other autoimmune disease (psoriatic arthritis, lupus, mixed connective disorder) or arthritis syndromes (gout, Lyme disease, Reiter’s syndrome);
c) recent (within past 2 months prior to Day 1 dosing) serious surgery or infectious disease;
d) recent history (past 5 years prior to Day 1 dosing) of, or treatment for, a malignancy other than nonmelanomatous skin cancer, or any history of lymphoma;
e) Hepatitis B surface antigen positive;
f) Hepatitis C antibody positive; may be included if Hepatitis C RIBA negative or HCV RNA negative (qualitative);
g) interstitial pneumonitis or active pulmonary infection on chest x-ray (taken within 1 month prior to screening);
h) Tuberculosis (TB): the TB skin test should be negative (if the patient was never vaccinated, or if vaccinated more than 10 years ago; in this context negative means < 5 mm induration); if the TB skin test is positive (in an unvaccinated patient), an appropriate prophylactic anti-TB regimen must be documented: Patients should have completed anti-TB treatment 1 year prior to Day 1 dosing. For vaccinated patients, if the vaccination was less than 10 years ago and the skin test is positive, an exception may be requested if the induration is < 10mm, the chest x-ray shows no sign of TB as confirmed by a radiologist, or the patient has had a course of Isoniazid (or comparable regimen).
i) known laboratory abnormalities: ALT > 1.2x ULN, creatinine >1.5x ULN, an ANC < 2,500/mm3 or lymphocyte count < 600/mm3, Hgb <9 g/dL, platelet count < 125,000/mm3 are excluded.
2) The patient has a history of substance abuse, drug addiction or alcoholism. Patients may consume up to 4 units of alcohol per week; however, alcohol should be avoided in the 72 hours prior to lab assessments. Patients who cannot reliably comply with this should be excluded. A unit of alcohol is defined as the following: Beer=12 oz or 355 mL; wine = 5 oz or 148 mL; sweet dessert wine=3 oz or 89 mL; 80 proof distilled spirits= 1.5 oz or 44 mL.
3) The patient has been treated previously treated with R788 under a different protocol.
4) The patient has a pacemaker, aneurysm clip or other contraindication to MRI.


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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: R935788
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Fostamatinib Disodium
CAS Number: 914295-16-2
Current Sponsor code: R935788 sodium hexahydrate
Other descriptive name: R788 Sodium, R788 Na, R788
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

Primary Outcome(s)

Main Objective: The primary objective of this study is to assess the efficacy of R788 100 mg PO bid compared with placebo, as determined by ACR20 responder rates at Month 3.

Primary end point(s): The Primary Efficacy parameter is ACR20 response rate at Month 3 post dosing. A patient will be defined as an ACR responder if he or she shows at least 20% improvement from baseline in both tender and swollen joint counts, and at least 20% improvement in any 3 of the following 5 criteria:
1) Physician global assessment of disease activity (VAS)
2) Patient global assessment of disease activity (VAS)
3) Patient reported pain score (VAS)
4) Health Assessment Questionnaire Disability Index (HAQ-DI)
5) C-reactive protein (CRP) or ESR

Secondary Objective: The secondary objectives of this study are as follows:
1) To assess the response rate of R788 100 mg PO bid as determined by ACR50, ACR70, ACRn, DAS28-CRP, and DAS28-ESR at Month 3;
2) To assess the rapidity of onset of clinical effect of R788 100 mg PO bid compared with placebo as determined by ACR20 response rates at Weeks 1 and 2;
3) To assess the radiologic response of R788 100 mg PO bid compared with placebo as determined by Magnetic Resonance Imaging (MRI) using the modified RAMRIS scoring system of the hand and wrist at Month 3;
4) To assess and compare the safety profiles of R788 100 mg PO bid dose with placebo for effects on liver function tests, clinically significant reduction in peripheral neutrophil counts, G-I side effects and other adverse effects as they may appear.

Secondary ID(s)

2008-000743-34-BE

C-935788-011

Ethics review

Status: Approved
Approval date: 21/07/2008
Contact: