A Phase 2a, Randomised, Double-blind, Parallel Study to Assess the Efficacy, Safety and Tolerability of AZD9567 Compared to Prednisolone 20 mg in Patients With Active Rheumatoid Arthritis (RA)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Least Square (LS) Mean Change From Baseline in 28 Joint Disease Activity Score Using C-Reactive Protein (DAS28-CRP) at Day 15
研究概览
简要总结
This is a phase 2a study to be run in 2-3 countries in European Union involving 5-6 sites. It will enroll approximately 80 patients to ensure 40 randomized with active rheumatoid arthritis. The treatment period is 2 weeks and total study duration per patient is approximately 1 month. The study drugs are AZD9567 40 mg (an oral SGRM) and the comparator is prednisolone 20mg. The primary endpoint is DAS28 including evaluation of 28 joints and C-reactive protein. Safety parameters will also be evaluated and a biomarker program is included for future research.
详细描述
This randomized double blind with double dummy technique phase 2a study will be run in 2-3 EU countries, most likely Sweden, Denmark and The Netherlands involving 5-6 sites. It is estimated that 80-100 patients have to be enrolled to ensure the randomization target of 40. The study population is patients with rheumatoid arthritis on stable treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) with an active flare. It is a two-arm parallel study and the randomization ratio is 1:1 to the two weeks of once daily treatment of 40 mg of AZD9567 and 20 mg prednisolone.
The primary objective is to assess the efficacy of AZD9567 40 mg, compared to prednisolone 20 mg in patients with active rheumatoid arthritis in spite of stable treatment with conventional and/or s.c/i.v. biological DMARDs and the primary variable is change from baseline in 28 joint Disease Activity Score using CRP (DAS28 - CRP). As secondary variables swollen and tenderness of 66-68 joints and safety variables are also included. For exploratively purposes there is also a biomarker program, collecting blood samples for future research.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double dummy technique
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Established RA diagnosis according to the 2010 American College of Rheumatology (ACR)/EULAR classification or the 1987 criteria
- •Active RA (DAS28-CRP score ≥ 3.2) with at least 3 swollen joints and 3 tender joints using the DAS28 joint count
- •Patients must have be on stable dosing of conventional and/or s.c./i.v biological DMARDs for the last 8 weeks prior to Visit 1
- •CRP levels >5mg/L at screening if seronegative for Rheumatoid Factor (RF) and Anti-Cyclic Citrullinated Peptide antibody (anti-CCP Ab), or >2mg/L if seropositive for either marker
- •BMI between 18 and 35 (inclusive)
- •Negative pregnancy test (serum) for female subjects of childbearing potential
排除标准
- •History or current inflammatory rheumatic disease other than RA (secondary Sjogren's syndrome excluded)
- •History or current clinically important disease which may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
- •Any clinical contraindications to treatment with steroids
- •Oral or parenteral steroids (beyond study medication) 8 weeks prior to study start and during the study. Stable use and dose of topical and inhaled steroids for longer than 4 w prior to randomization is acceptable
- •Use of any prohibited medication during the study or if the required washout time of such medication was not adhered to
- •History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar class to study drugs
- •Any concomitant medications that are known to be associated with Torsades de Pointes
研究组 & 干预措施
AZD9567
oral suspension of 40 mg AZD9567 once daily (OD) for two weeks
干预措施: AZD9567 (Drug)
Prednisolone
oral OD treatment of 20 mg prednisolone administered as capsules
干预措施: Prednisolone (Drug)
结局指标
主要结局
Least Square (LS) Mean Change From Baseline in 28 Joint Disease Activity Score Using C-Reactive Protein (DAS28-CRP) at Day 15
时间窗: Baseline (Day 1) and Day 15
The DAS28-CRP is a measure of disease activity in RA. The score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment (PGA) of health (ranging from very well to very poor). The DAS28-CRP was derived as follows: 0.56 x √\[tender joint count 28 (TJC28)\] + 0.28 x √\[swollen joint count 28 (SJC28)\] + 0.014 x global health (GH) + 0.36 x Ln(CRP+1) + 0.96 to produce the overall DAS28-CRP score on a scale ranged from 0-10 with higher score indicating worse RA symptoms. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
次要结局
- LS Mean Change From Baseline in TJC68 Score at Day 15(Baseline and Day 15)
- LS Mean Change From Baseline in CRP at Day 15(Baseline and Day 15)
- Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses(Day 15)
- LS Mean Change From Baseline in SJC66 Score at Day 15(Baseline and Day 15)
- LS Mean Change From Baseline in TJC28 Score at Day 15(Baseline and Day 15)
- LS Mean Change From Baseline in GH Score at Day 15(Baseline and Day 15)
- LS Mean Change From Baseline in Participant's Assessment of Pain Score at Day 15(Baseline and Day 15)
- Last Plasma Concentration Measured Before the Last Dose (Ctrough) of AZD9567(Predose on Day 15)
- LS Mean Change From Baseline in SJC28 Score at Day 15(Baseline and Day 15)
- LS Mean Change From Baseline in Physician's Global Assessment of Disease Activity Score at Day 15(Baseline and Day 15)
- LS Mean Change From Baseline in Participant's Assessment of Physical Function Score at Day 15(Baseline and Day 15)
- Area Under the Plasma Concentration-Time Curve Until the Last Quantifiable Concentration (AUClast) of AZD9567(Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.)
- Area Under the Concentration-Time Curve From Time Zero to 6 Hours After Dose (AUC0-6) of AZD9567(Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.)
- Maximum Observed Plasma Concentration (Cmax) of AZD9567(Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.)
- Time to Reach Maximum Plasma Concentration (Tmax) of AZD9567(Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.)