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Investigating AZD5492 for treating systemic lupus erythematosus and inflammatory myopathies

An Open-label, Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD5492 Following Single-ascending Dose and Step-up Dose Administration to Adult Participants With Systemic Lupus Erythematosus or Idiopathic Inflammatory Myopathies or Rheumatoid Arthritis

Phase 1 Interventional AstraZeneca · NCT06916806

This study is testing a new medication called AZD5492 to see if it can safely help adults with systemic lupus erythematosus and inflammatory myopathies feel better.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment72 (estimated)
Ages18 Years to 70 Years
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionsbelimumab, anifrolumab, ocrelizumab, ofatumumab, obinutuzumab, rituximab, methotrexate, cyclophosphamide
Locations35 sites (Anniston, Alabama and 34 other locations)
Trial IDNCT06916806 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD5492 in adult participants diagnosed with systemic lupus erythematosus (SLE) or idiopathic inflammatory myopathies (IIM). The study is divided into two parts: Part 1 involves a single ascending dose design for participants with SLE, while Part 2 includes a step-up dosing regimen for participants with SLE and IIM. Participants will be monitored over a minimum of 180 days, with follow-up visits extending up to 12 months. The trial will take place across approximately 20 sites in 8 countries.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 65 with active, moderate to severe systemic lupus erythematosus or idiopathic inflammatory myopathies who have not responded adequately to existing treatments.

Not a fit: Patients with mild forms of systemic lupus erythematosus or idiopathic inflammatory myopathies, or those who have not tried multiple existing therapies, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients suffering from systemic lupus erythematosus and idiopathic inflammatory myopathies.

How similar studies have performed: Other studies have explored treatments for systemic lupus erythematosus and inflammatory myopathies, but the specific approach of AZD5492 in this context is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Anniston, Alabama and 34 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Systemic Lupus ErythematosusIdiopathic Inflammatory MyopathiesRheumatoid ArthritisLupusInflammatory MyopathyMusculoskeletal DiseasesNeuromuscular DiseasesNervous System Diseases
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.