Early Phase Study to Assess Efficacy and Safety of AZD9567 Versus Prednisolone in Patients With Rheumatoid Arthritis

NCT03368235 | Completed Phase 2 Results

• 1 other identifier: D6470C00003
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 5

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.

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis, swollen joints, tender joints, autoimmunity

Outcome Measures

Primary Outcomes (1)

• Least Square (LS) Mean Change From Baseline in 28 Joint Disease Activity Score Using C-Reactive Protein (DAS28-CRP) at 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.

  Baseline (Day 1) and Day 15

Secondary Outcomes (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 TJC68 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 SJC28 Score at Day 15

  Baseline and Day 15

Study Arms (2)

AZD9567

EXPERIMENTAL

oral suspension of 40 mg AZD9567 once daily (OD) for two weeks

Drug: AZD9567

Prednisolone

ACTIVE COMPARATOR

oral OD treatment of 20 mg prednisolone administered as capsules

Drug: Prednisolone

Interventions

AZD9567 DRUG

oral OD SGRM administered as suspension

AZD9567

Prednisolone DRUG

oral capsules of 20 mg prednisolone administered OD for two weeks

Prednisolone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (5)

Research Site

Enschede, 7512 KZ, Netherlands

Location

Research Site

Maastricht, 6229 HX, Netherlands

Location

Research Site

Utrecht, 3584 CX, Netherlands

Location

Research Site

Gothenburg, 413 45, Sweden

Location

Research Site

Lund, 221 85, Sweden

Location

Related Links

• Redacted Protocol
• SAP

MeSH Terms

Conditions

Arthritis, Rheumatoid; Autoimmune Diseases

Interventions

AZD9567; Prednisolone

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Jacob M Van Laar, Professor

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double dummy technique
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double blind, parallell arm study with two weeks treatment of AZD9567 or prednisolone

Study Record Dates

• First Submitted: November 3, 2017
• First Posted: December 11, 2017
• Study Start: January 18, 2018
• Primary Completion: November 12, 2019
• Study Completion: November 12, 2019
• Last Updated: October 5, 2020
• Results First Posted: October 5, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); NL (3)