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.

NCT06916806 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: D9961C000012024-519015-34-00
• Study Type: interventional
• Target: 72
• Locations: 9 countries
• Sites: 35

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

Keywords

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

Outcome Measures

Primary Outcomes (8)

• Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events.

  Number and percentage of participants with AEs, AESIs, and SAEs

  Day 1 to end of the study (up to 52 weeks)

• Safety evaluation of AZD5492: Number of participants with related treatment-emergent adverse events.

  Number and percentage of participants with AEs related to IMP as assessed by the investigator

  Day 1 to end of the study (up to 52 weeks)

• Safety evaluation of AZD5492: Frequency of dose limiting toxicities (DLTs).

  Number and percentage of participants with DLTs (dose-limiting toxicities) as defined in the study protocol.

  Day 1 to end of the study (up to 52 weeks)

• Safety evaluation of AZD5492: Number of SAEs leading to death

  Number and percentage of participants with 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.

  Number and percentage of participants with AEs according ASTCT, IEC-HS, and CTCAE grades.

  Day 1 to end of the study (up to 52 weeks)

• Tolerability evaluation of AZD5492: Number of participants with treatment-emergent vital signs abnormalities.

  Number and percentage of participants with treatment-related vital signs abnormalities.

  Day 1 to end of the study (up to 52 weeks)

• Tolerability evaluation of AZD5492: Number of participants with treatment-emergent clinical laboratory abnormalities.

  Number and percentage of participants with treatment-related clinical laboratory abnormalities.

  Day 1 to end of the study (up to 52 weeks)

• Tolerability evaluation of AZD5492: Number of participants with abnormal ECG.

  Number and percentage of participants with abnormal ECG.

  From Day 1 up to Day 180

Secondary Outcomes (6)

• 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

Study Arms (2)

Part 1: Single Ascending Dose with AZD5492

EXPERIMENTAL

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

Drug: AZD5492

Part 2: Step-Up Dosing with AZD5492

EXPERIMENTAL

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.

Drug: AZD5492

Interventions

AZD5492 DRUG

IMP: subcutaneous.

Part 1: Single Ascending Dose with AZD5492; Part 2: Step-Up Dosing with AZD5492

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent.
• Diagnosis of SLE:
• Diagnosis of SLE according to the 2019 EULAR/ACR classification criteria for SLE
• Positive for one or more of: anti-nuclear antibodies (titre ≥ 1:80), anti-dsDNA or anti-Sm at screening.
• Active, moderate-severe disease at screening, defined as clinical SLEDAI-2K ≥ 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.
• Diagnosis of IIM:
• 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.
• Positive for ≥ 1 disease-specific autoantibody at screening.
• MMT-8 score of ≤ 142/150 and/or CDASI-A ≥ 6
• 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.
• 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.

You may not qualify if:

• 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:
• Active severe SLE-driven renal disease.
• 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.
• Rapidly progressive and/or severe ILD or ILD that requires oxygen supplementation/therapy (of any type).
• Active severe, unstable or history of neuropsychiatric SLE.
• 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:
• FVC ≤60% of predicted
• DLCO ≤70% of predicted
• Deterioration in either FVC or DLCO at screening compared to pulmonary function tests performed ≥3 months previously.
• Significant history of or at risk of severe infections.
• Participants with HIV infection.
• Participants with evidence of chronic or active hepatitis B defined as HBsAg positive or HBcAB positive
• Participants with evidence of chronic or active hepatitis C
• Participants with positive COVID-19 PCR.
• Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection.

Sponsors & Collaborators

• Fortrea: collaborator
• AstraZeneca: lead

Study Sites (35)

Research Site

Anniston, Alabama, 36207, United States

RECRUITING

Research Site

Birmingham, Alabama, 35233, United States

WITHDRAWN

Research Site

La Jolla, California, 92037, United States

NOT YET RECRUITING

Research Site

Sacramento, California, 95817, United States

NOT YET RECRUITING

Research Site

Iowa City, Iowa, 52242, United States

RECRUITING

Research Site

Chapel Hill, North Carolina, 27599, United States

NOT YET RECRUITING

Research Site

Hamilton, Ontario, L8S 4K1, Canada

NOT YET RECRUITING

Research Site

Sherbrooke, Quebec, J1G 2E8, Canada

RECRUITING

Research Site

Beijing, 100730, China

RECRUITING

Research Site

Shanghai, 200001, China

RECRUITING

Research Site

Wuhan, 430022, China

RECRUITING

Research Site

Zhengzhou, 450052, China

NOT YET RECRUITING

Research Site

Bordeaux, 33000, France

RECRUITING

Research Site

Montpellier, 34295, France

RECRUITING

Research Site

Nancy, 54035, France

RECRUITING

Research Site

Paris, 75013, France

RECRUITING

Research Site

Strasbourg, 67098, France

RECRUITING

Research Site

Toulouse, 31059, France

RECRUITING

Research Site

Cologne, 50937, Germany

NOT YET RECRUITING

Research Site

Erlangen, 91054, Germany

NOT YET RECRUITING

Research Site

Magdeburg, 39120, Germany

NOT YET RECRUITING

Research Site

Bunkyō City, 113-8655, Japan

RECRUITING

Research Site

Kita-gun, 761-0793, Japan

RECRUITING

Research Site

Kitakyushu-shi, 807-8555, Japan

RECRUITING

Research Site

Kyoto, 606-8501, Japan

RECRUITING

Research Site

Nagasaki, 852-8501, Japan

RECRUITING

Research Site

Amsterdam, 1105 AZ, Netherlands

RECRUITING

Research Site

Leiden, 2333, Netherlands

WITHDRAWN

Research Site

Mérida, 06800, Spain

RECRUITING

Research Site

Seville, 41010, Spain

RECRUITING

Research Site

Valladolid, 47012, Spain

RECRUITING

Research Site

Glasgow, G31 2ER, United Kingdom

RECRUITING

Research Site

London, SE5 9RS, United Kingdom

RECRUITING

Research Site

London, WC1E 6JF, United Kingdom

RECRUITING

Research Site

Southampton, SO16 6YD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Myositis; Arthritis, Rheumatoid; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Muscular Diseases; Dermatomyositis; Polymyositis; Arthritis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Joint Diseases; Rheumatic Diseases; Skin Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-Label, single-arm treatment study.

Study Record Dates

• First Submitted: March 13, 2025
• First Posted: April 8, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): May 5, 2027
• Study Completion (Estimated): September 15, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

CA (2); CN (4); DE (3); NL (2); JP (5); FR (6); US (6); ES (3); GB (4)