Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate and Have Had Inadequate Response to Single TNF-alpha Antagonist (OSKIRA - 3)

• Register: EUCTR
• Last refreshed on: 29 April 2013
• Main ID: EUCTR2010-020745-27-CZ
• Date of registration: 30/08/2010
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate and Have Had Inadequate Response to Single TNF-alpha Antagonist (OSKIRA - 3)
• Scientific title: A Phase III, Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of Two Dosing Regimens of Fostamatinib Disodium in Rheumatoid Arthritis Patients with Inadequate Response to a TNF-alpha antagonist - OSKIRA - 3
• Date of first enrolment: 11/10/2010
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020745-27
• 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

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Mexico, Portugal, South Africa, Spain, United Kingdom, United States

Contacts

• Name: Information Centre
• Affiliation: AstraZeneca AB

• Name: Information Centre
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female aged 18 and over
2. A diagnosis of RA after the age of 16
3. Currently taking methotrexate
4. Currently receiving, or have previously received, a single TNF-alpha antagonist for the treatment of RA
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 405
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion criteria:
1.Females who are pregnant or lactating
2.Any systemic inflammatory conditions (other than RA),connective tissue disease or chronic pain disorders that may interfere with the interpretation of the outcome data
3.Poorly controlled blood pressure
4.History of liver function abnormality requiring investigation


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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 13.1 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: Fostamatinib disodium
Product Code: FosD
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Fostamatinib disodium
CAS Number: 914295-16-2
Current Sponsor code: FosD
Other descriptive name: Fostamatinib disodium
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
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 evaluate the efficacy of 2 oral dosing regimens of fostamatinib (Regimen A - 100 mg twice daily (bid); Regimen B - induction with 100 mg bid for the first 4 weeks, 150 mg once daily (qd) maintenance thereafter) taken in combination with methotrexate, compared with placebo plus methotrexate, in patients with active rheumatoid arthritis (RA) who have had inadequate response to a single tumour necrosis factor-alpha (TNF-a) antagonist.

Timepoint(s) of evaluation of this end point: Week 24

Primary end point(s): The primary endpoint in this study is the proportion of patients achieving ACR20 at Week 24. This will be assessed for each dose regimen versus placebo.

Secondary Objective: The secondary objectives of the study are:
•To further assess the efficacy of fostamatinib measured by ACR20, ACR 50% response criteria (ACR50), ACR 70% response criteria (ACR70), ACR-N and the individual components of the ACR score.
•To assess physical function status of patients after administration of fostamatinib using the Health Assessment Questionnaire - Disability Index (HAQ-DI).
•To evaluate the efficacy of fostamatinib as measured by Disease Activity Score based on a 28 joint count (DAS28) and DAS28 European League Against Rheumatism (EULAR) response criteria.
•To investigate the effects of fostamatinib on patient reported health outcomes measures.
•To assess the efficacy of fostamatinib in the prevention of structural joint damage, as measured by change in radiographic modified total Sharp score (mTSS) and the components of mTSS at Week 24.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Secondary timepoints are: Screening plus week 0-6, 12 and 24

For mTSS JSN (X-ray) timepoints Week 0, 12 and 24.

Secondary end point(s): - ACR20, ACR50, ACR70, major clinical response, ACR-N, individual
components of ACR (swollen joint count, tender joint count, patient’s
assessment of pain, patient’s global assessment of disease activity, physician’s global assessment of disease activity, patient’s assessment of physical function, as measured by the HAQ-DI, C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR])
- HAQ-DI score; HAQ-DI response, individual dimensions of HAQ-DI
- DAS28 response, DAS28 EULAR response criteria, DAS low disease activity, DAS28 remission, clinically important change in DAS28 score
- mTSS, radiographic erosion score (ES) and joint space narrowing (JSN).

Secondary ID(s)

2010-020745-27-GB

D4300C00003

NCT01197755

Source(s) of Monetary Support

AstraZeneca AB