Clinical trial NCT03368235: Early Phase Study to Assess Efficacy and Safety of AZD9567 Versus Prednisolone in Patients With Rheumatoid Arthritis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis, swollen joints, tender joints, autoimmunity
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2017-12-11
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double blind, parallell arm study with two weeks treatment of AZD9567 or prednisolone
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Established RA diagnosis according to the 2010 American College of Rheumatology (ACR)/EULAR classification or the 1987 criteria
2. Active RA (DAS28-CRP score ≥ 3.2) with at least 3 swollen joints and 3 tender joints using the DAS28 joint count
3. 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
4. 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
5. BMI between 18 and 35 (inclusive)
6. Negative pregnancy test (serum) for female subjects of childbearing potential

Exclusion Criteria:

1. History or current inflammatory rheumatic disease other than RA (secondary Sjogren's syndrome excluded)
2. 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
3. Any clinical contraindications to treatment with steroids
4. 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
5. Use of any prohibited medication during the study or if the required washout time of such medication was not adhered to
6. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar class to study drugs
7. Any concomitant medications that are known to be associated with Torsades de Pointes

Primary outcomes:
measure: Least Square (LS) Mean Change From Baseline in 28 Joint Disease Activity Score Using C-Reactive Protein (DAS28-CRP) at Day 15
timeFrame: Baseline (Day 1) and Day 15
Secondary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses
timeFrame: Day 15
measure: LS Mean Change From Baseline in SJC66 Score at Day 15
timeFrame: Baseline and Day 15
measure: LS Mean Change From Baseline in TJC68 Score at Day 15
timeFrame: Baseline and Day 15
measure: LS Mean Change From Baseline in TJC28 Score at Day 15
timeFrame: Baseline and Day 15
measure: LS Mean Change From Baseline in SJC28 Score at Day 15
timeFrame: Baseline and Day 15
measure: LS Mean Change From Baseline in GH Score at Day 15
timeFrame: Baseline and Day 15
measure: LS Mean Change From Baseline in CRP at Day 15
timeFrame: Baseline and Day 15
measure: LS Mean Change From Baseline in Participant's Assessment of Pain Score at Day 15
timeFrame: Baseline and Day 15
measure: LS Mean Change From Baseline in Physician's Global Assessment of Disease Activity Score at Day 15
timeFrame: Baseline and Day 15
measure: LS Mean Change From Baseline in Participant's Assessment of Physical Function Score at Day 15
timeFrame: Baseline and Day 15
measure: Area Under the Plasma Concentration-Time Curve Until the Last Quantifiable Concentration (AUClast) of AZD9567
timeFrame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
measure: Area Under the Concentration-Time Curve From Time Zero to 6 Hours After Dose (AUC0-6) of AZD9567
timeFrame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
measure: Maximum Observed Plasma Concentration (Cmax) of AZD9567
timeFrame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
measure: Time to Reach Maximum Plasma Concentration (Tmax) of AZD9567
timeFrame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
measure: Last Plasma Concentration Measured Before the Last Dose (Ctrough) of AZD9567
timeFrame: Predose on Day 15
Other outcomes:
Locations:
city: Enschede
country: Netherlands
facility: Research Site
city: Maastricht
country: Netherlands
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
Study officials:
affiliation: UMC Utrecht
name: Jacob M Van Laar, Professor
role: PRINCIPAL_INVESTIGATOR
References: