Back to Trials
NCT06916806PHASE1Recruiting

A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD5492 in Adult Participants With Systemic Lupus Erythematosus or Idiopathic Inflammatory Myopathies or Rheumatoid Arthritis.

AstraZeneca

Start Date

5/1/2025

Completion Date

9/15/2027

Summary

The purpose of this study is to measure the safety, tolerability, PK, and PD of AZD5492 administered subcutaneously in adult participants with SLE or IIM or RA Study details include: • The study duration will be a minimum of 180 days in addition to the screening period. Additional follow-up visits may be required up to 12 months from study start. * Depending on the study part they are assigned to, participants will be administered AZD5492 once (Part 1) or twice (Part 2). * Study visits will occur at: Screening, Days 1-4, 8, 15, 22, 30, 60, 90, 120, 150, and 180 in Part 1, Screening, Days 1-4, 8-11, 15, 22, 29, 43, 60, 90, 120, 150, and 180 in Part 2.

Detailed Description

This is an open-label, multi-centre Phase I study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD5492 in adult participants with either SLE or IIM or RA. The study consists of 2 parts: Part 1 - Single ascending dose (SAD) Part 1 will be a sequential SAD design in adult participants with SLE. Up to 5 dose levels of AZD5492 are planned to be investigated. Depending on emerging data, up to 4 additional dose levels may be added at the discretion of the Sponsor. The decision to open Part 2 will be made by the Safety Review Committee (SRC) based on the evaluation of all available data including safety, tolerability, PK, and PD from Part 1 and pertinent data arising from other ongoing studies with AZD5492 will also be considered, and the dose levels and dosing strategy for Part 2 will be confirmed. After a screening period of up to 42 days, participants will receive 1 dose of AZD5492 and be followed up for at least 179 days post-dose. Part 2 - Step-up dosing (SUD) Part 2 will be a SUD design in adult participants who have SLE (and did not participate in Part 1), as well as adult participants with IIM or RA. In Part 2, participants will receive 2 dose administrations, 7 days apart. The first (priming) dose of the step-up regimen will be agreed by the SRC. The second (target) dose will be escalated, and a minimum of 3 target dose levels are planned to be investigated in Part 2.

Eligibility Criteria

Age Range: 18 years to 70 years

Inclusion Criteria: 1. Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent. 2. Diagnosis of SLE: 1. Diagnosis of SLE according to the 2019 EULAR/ACR classification criteria for SLE 2. Positive for one or more of: anti-nuclear antibodies (titre ≥ 1:80), anti-dsDNA or anti-Sm at screening. 3. Active, moderate-severe disease at screening, defined as clinical SLEDAI-2K ≥ 4. 4. Intolerance to, or inadequate response following at least 3 months of use to, ≥ 3 available treatments, such as the following: corticosteroids, anti-malarial drugs, calcineurin inhibitor, methotrexate, azathioprine, leflunomide, mycophenolic acid or its derivatives, cyclophosphamide, belimumab, anifrolumab, telitacicept, or B-cell depleting monoclonal antibodies. 3. Diagnosis of IIM: 1. Must have "probable" or "definite" diagnosis of PM or DM (excluding IBM and cancer associated myositis) according to the 2017 EULAR/ACR classification criteria for adult myositis. 2. Positive for ≥ 1 disease-specific autoantibody at screening. 3. MMT-8 score of ≤ 142/150 and/or CDASI-A ≥ 6 4. Fulfill at least one of the following criteria of active disease at screening: (i) One or more muscle enzyme elevation (CK, AST, ALT, aldolase, LDH) ≥ 1.3 × ULN (ii) If criterion 3(d)(i) is not met, then at least one of the following criteria must be met: a. Report from MRI performed within 3 months prior to screening with evidence of muscle inflammation b. Report from muscle biopsy performed within 3 months prior to screening that demonstrates active inflammation c. Report from electromyography performed within 3 months prior to screening that exhibits irritable myopathic pattern. (e) Intolerance or inadequate response to corticosteroids and ≥2 other SoC treatments, used for at least 3 months each, for which at least one must be a biologic SoC, immunoglobulin or cyclophosphamide. 4. Diagnosis of RA: (a) Diagnosis of RA as defined by the 2010 EULAR/ACR classification criteria (b) Positive for ≥ 1 disease-specific autoantibody performed by the central laboratory at screening: RF or ACPA (c) Moderate or severe disease activity defined as: (i) ≥6 tender joints and ≥6 swollen joints AND (ii) DAS28-CRP \>3.2. (d) Intolerance to or inadequate response following approximately 3 month's treatment or longer to ≥2 b/tsDMARDs (with different mechanisms of action) after failing csDMARD therapy (unless csDMARD therapy is contraindicated). There is no minimum duration for taking a treatment in cases of intolerance. Exclusion Criteria: 1. Any complications of the disease under study which are judged by the investigator to be life or organ threatening or to require treatments which are not permitted in the protocol, including but not limited to: 1. Active severe SLE-driven renal disease. 2. History of, or current diagnosis of, catastrophic or severe APS (for example diagnosis of an arterial or central/pulmonary venous clot) within 1 year prior to signing the ICF. 3. Rapidly progressive and/or severe ILD or ILD that requires oxygen supplementation/therapy (of any type). 4. Inclusion Body Myositis or cancer associated myositis. 2. Active severe, unstable or history of neuropsychiatric SLE. 3. IIM: Pulmonary function tests at screening (or within one month of screening, provided participant confirms no change in respiratory symptoms in the interim) which meet any of the following criteria: 1. FVC ≤60% of predicted 2. DLCO ≤70% of predicted 3. Deterioration in either FVC or DLCO at screening compared to pulmonary function tests performed ≥3 months previously. 4. Significant history of or at risk of severe infections. 5. Participants with HIV infection. 6. Participants with evidence of chronic or active hepatitis B defined as HBsAg positive or HBcAB positive 7. Participants with evidence of chronic or active hepatitis C 8. Participants with positive COVID-19 PCR. 9. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection. 10. Significant CNS pathology. 11. Receipt of B-cell-depleting therapy including CD19 or CD20 directed monoclonal antibodies (including but not limited to, ocrelizumab, ofatumumab, obinutuzumab, or rituximab) \<3 months prior to Day 1.

Interventions

DRUG

AZD5492

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Systemic Lupus ErythematosusIdiopathic Inflammatory MyopathiesRheumatoid Arthritis

Locations

Research Site

Anniston, Alabama 36207

United States

Research Site

Birmingham, Alabama 35233

United States

Research Site

La Jolla, California 92037

United States

Research Site

Sacramento, California 95817

United States

Research Site

Iowa City, Iowa 52242

United States

Research Site

Omaha, Nebraska 68198

United States

Research Site

Chapel Hill, North Carolina 27599

United States

Research Site

Hamilton, Ontario L8S 4K1

Canada

Research Site

Sherbrooke, Quebec J1G 2E8

Canada

Research Site

Beijing, 100730

China

Research Site

Shanghai, 200001

China

Research Site

Wuhan, 430022

China

Research Site

Zhengzhou, 450052

China

Research Site

Bordeaux, 33000

France

Research Site

Montpellier, 34295

France

Research Site

Nancy, 54035

France

Research Site

Paris, 75013

France

Research Site

Strasbourg, 67098

France

Research Site

Toulouse, 31059

France

Research Site

Cologne, 50937

Germany

Research Site

Erlangen, 91054

Germany

Research Site

Magdeburg, 39120

Germany

Research Site

Pok Fu Lam, 999077

Hong Kong

Research Site

Bunkyō City, 113-8655

Japan

Research Site

Kita-gun, 761-0793

Japan

Research Site

Kitakyushu-shi, 807-8555

Japan

Research Site

Kyoto, 606-8501

Japan

Research Site

Nagasaki, 852-8501

Japan

Research Site

Amsterdam, 1105 AZ

Netherlands

Research Site

Leiden, 2333

Netherlands

Research Site

Mérida, 06800

Spain

Research Site

Seville, 41010

Spain

Research Site

Valladolid, 47012

Spain

Research Site

Glasgow, G31 2ER

United Kingdom

Research Site

London, SE5 9RS

United Kingdom

Research Site

London, WC1E 6JF

United Kingdom

Research Site

Southampton, SO16 6YD

United Kingdom