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

Plain English Summary

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. is a Phase 1 clinical trial sponsored by AstraZeneca studying Systemic Lupus Erythematosus, Idiopathic Inflammatory Myopathies, Rheumatoid Arthritis. This study tests the safety and tolerability of a new drug called AZD5492 in adults. It is for individuals diagnosed with Systemic Lupus Erythematosus (SLE), Idiopathic Inflammatory Myopathies (IIM), or Rheumatoid Arthritis (RA). Participants will receive AZD5492 via injection, with varying doses and schedules depending on the study part. Alternative treatments include corticosteroids, biologics, and other disease-modifying drugs, depending on the specific condition. The trial aims to enroll 72 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18-70 with a confirmed diagnosis of SLE, IIM, or RA. Patients must have active disease that has not responded adequately to or is intolerant of current standard treatments. Specific autoantibodies and disease activity scores are required for each condition. Individuals with severe organ-threatening complications, certain infections (HIV, Hepatitis B/C, COVID-19), or significant neurological issues may not be eligible. This trial is studying Systemic Lupus Erythematosus, Idiopathic Inflammatory Myopathies, Rheumatoid Arthritis, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe AZD5492 is by tracking any side effects, serious adverse events, and dose-limiting toxicities, ensuring patient well-being during treatment. The specific primary outcome measures are: Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events. (Day 1 to end of the study (up to 52 weeks)); Safety evaluation of AZD5492: Number of participants with related treatment-emergent adverse events. (Day 1 to end of the study (up to 52 weeks)); Safety evaluation of AZD5492: Frequency of dose limiting toxicities (DLTs). (Day 1 to end of the study (up to 52 weeks)); Safety evaluation of AZD5492: Number of SAEs leading to death (Day 1 to end of the study (up to 52 weeks)); Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events by grade. (Day 1 to end of the study (up to 52 weeks)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial is important for filling a treatment gap by investigating a new therapy for debilitating autoimmune conditions like lupus, inflammatory myopathies, and rheumatoid arthritis. This research targets Systemic Lupus Erythematosus, Idiopathic Inflammatory Myopathies, Rheumatoid Arthritis, where improved treatment options are needed.

Investor Insight

This Phase 1 study is an early step in drug development, focusing on safety and tolerability, which are crucial for determining the potential of AZD5492 in a market with significant unmet needs for au Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the study's goals, potential risks and benefits, and what participation involves. Be prepared for regular study visits for injections, blood draws, and health assessments over approximately 6 months, with potential follow-up. Understand that this is an open-label study, meaning both you and the research team will know you are receiving AZD5492. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 72 participants

Interventions

• DRUG: AZD5492 — IMP: subcutaneous.

Primary Outcomes

• Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events. (Day 1 to end of the study (up to 52 weeks))
• Safety evaluation of AZD5492: Number of participants with related treatment-emergent adverse events. (Day 1 to end of the study (up to 52 weeks))
• Safety evaluation of AZD5492: Frequency of dose limiting toxicities (DLTs). (Day 1 to end of the study (up to 52 weeks))
• Safety evaluation of AZD5492: Number of SAEs leading to death (Day 1 to end of the study (up to 52 weeks))
• Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events by grade. (Day 1 to end of the study (up to 52 weeks))

Secondary Outcomes

• Serum Pharmacokinetics (PK) parameters of AZD5492 (Cmax) (From Day 1 through Day 60)
• Serum Pharmacokinetics (PK) parameters of AZD5492 (AUC) (From Day 1 through Day 60)
• Serum Pharmacokinetics (PK) parameters of AZD5492 (t1/2λz) (From Day 1 through Day 60)
• Serum Pharmacokinetics (PK) parameters of AZD5492 (AUClast) (From Day 1 through Day 60)
• Incidence of ADAs to AZD5492 measured in serum. (From Day 1 through Day 180)

Full 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.

Trial Locations

• Research Site, Anniston, Alabama, United States
• Research Site, Birmingham, Alabama, United States
• Research Site, La Jolla, California, United States
• Research Site, Sacramento, California, United States
• Research Site, Iowa City, Iowa, United States
• Research Site, Hamilton, Ontario, Canada
• Research Site, Sherbrooke, Quebec, Canada
• Research Site, Beijing, China
• Research Site, Shanghai, China
• Research Site, Wuhan, China
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Systemic Lupus Erythematosus
• Idiopathic Inflammatory Myopathies
• Rheumatoid Arthritis
• Autoimmune Diseases
• Connective Tissue Diseases
• Inflammation
• Immunology
• Dermatology
• Rheumatology
• Nephrology

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