RecruitingPhase 1

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.

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 70 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 12 months, 42 days

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "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), twice (Part 2a), or three times (Part 2b)."
  • "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."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the safety of AZD5492, how well people handle it, and how it moves through and affects the body. It is for adults with lupus, certain diseases that cause muscle swelling, or rheumatoid arthritis. Participants get 1 to 3 shots under the skin, with follow-up for at least 180 days and possibly up to 12 months.

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), twice (Part 2a), or three times (Part 2b).

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be 18 to 70 years old when you agree to join.
  • Have a qualifying diagnosis of lupus, inflammatory muscle disease, or rheumatoid arthritis. Each disease has its own rules below.
  • For lupus: Have active, moderate to severe disease and a positive blood test for certain antibodies—proteins made by the immune system.
  • For lupus: Have been unable to handle at least 3 treatments, or have had too little benefit after at least 3 months of use.
  • For muscle disease: Have probable or definite polymyositis or dermatomyositis, which cause muscle swelling and sometimes a skin rash. Have a positive disease-related antibody test and meet the study's muscle strength or skin symptom score limits.
  • For muscle disease: Have tests showing active disease. Also, have been unable to handle or had too little benefit from steroids and at least 2 other standard treatments used for at least 3 months each. At least one must be a biologic drug, immunoglobulin, or cyclophosphamide.
  • For rheumatoid arthritis: Have a positive disease-related antibody test, at least 6 tender and 6 swollen joints, and a disease activity score above 3.2.
  • For rheumatoid arthritis: Have tried standard disease-slowing drugs without success, unless unsafe for you. Also, have been unable to handle or had too little benefit from at least 2 biologic or targeted drugs that work differently. Usually, each must have been tried for about 3 months.

Who can't join

  • Have disease problems that threaten life or organs, or need treatments not allowed in the study. Examples include severe active lupus kidney disease, severe clotting disease within the past year, or severe lung scarring.
  • Have inclusion body myositis or muscle disease linked to cancer.
  • Have severe active or unstable lupus affecting the brain or mental health, a history of this condition, or another major brain or spinal cord condition.
  • For muscle disease: Have breathing test results at or below the study limits, or results that have worsened since tests done at least 3 months earlier.
  • Have a major history of severe infections or a high risk of them, an inherited immune system weakness, a removed spleen, or another condition that raises infection risk.
  • Have HIV, blood tests showing hepatitis B, or evidence of ongoing hepatitis C.
  • Have a positive COVID-19 PCR test.
  • Have received treatment that removes B cells, a type of immune cell, less than 3 months before the first study dose.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility 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.

Study sites (7)

AL

CA

IA

NC

NE