Recruiting
Phase 1

AZD5492

Sponsor:

AstraZeneca

Code:

NCT06916806

Conditions

Systemic Lupus Erythematosus

Idiopathic Inflammatory Myopathies

Rheumatoid Arthritis

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

AZD5492

Study Details

Brief 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.

Conditions

Systemic Lupus Erythematosus

Idiopathic Inflammatory Myopathies

Rheumatoid Arthritis

Study ID

NCT06916806

Start date

May 1, 2025

Status verified date

Jul, 2026

Completion date

Sep 15, 2027

Anticipated

Primary completion date

May 5, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

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 Design

Enrollment

72 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1: Single Ascending Dose with AZD5492

Participants will receive AZD5492 at an assigned dose as subcutaneous (SC) injection on Day 1.

experimental: Part 2: Step-Up Dosing with AZD5492

Participants will receive AZD5492 as SC injection at the priming dose determined in Part 1, on Day 1, and at a target dose, based on the emergent safety data, on Day 8.

Interventions

AZD5492

IMP: subcutaneous.

Primary outcome measure

  • Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events. [ Time Frame: Day 1 to end of the study (up to 52 weeks) ]
  • Safety evaluation of AZD5492: Number of participants with related treatment-emergent adverse events. [ Time Frame: Day 1 to end of the study (up to 52 weeks) ]
  • Safety evaluation of AZD5492: Frequency of dose limiting toxicities (DLTs). [ Time Frame: Day 1 to end of the study (up to 52 weeks) ]
  • Safety evaluation of AZD5492: Number of SAEs leading to death [ Time Frame: 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. [ Time Frame: Day 1 to end of the study (up to 52 weeks) ]
  • Tolerability evaluation of AZD5492: Number of participants with treatment-emergent vital signs abnormalities. [ Time Frame: Day 1 to end of the study (up to 52 weeks) ]
  • Tolerability evaluation of AZD5492: Number of participants with treatment-emergent clinical laboratory abnormalities. [ Time Frame: Day 1 to end of the study (up to 52 weeks) ]
  • Tolerability evaluation of AZD5492: Number of participants with abnormal ECG. [ Time Frame: From Day 1 up to Day 180 ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

Anniston, Alabama, United States, 36207

Research Site

Recruiting

Iowa City, Iowa, United States, 52242

Research Site

Recruiting

Sherbrooke, Quebec, Canada, J1G 2E8

More Information

Sponsor

AstraZeneca

Last update posted

Jul 23, 2026

Last verified

Jul, 2026

Keywords

  • Lupus
  • Inflammatory Myopathy
  • Musculoskeletal Diseases
  • Neuromuscular Diseases
  • Nervous System Diseases
  • Muscular Diseases
  • Myositis
  • Dermatomyositis
  • Polymyositis
  • Arthritis

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-07-23.