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. (TITAN)

May 25, 2026 updated by: AstraZeneca

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, multi-centre Phase I study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD5492 in adult participants with either SLE or IIM or RA.

The study consists of 2 parts:

Part 1 - Single ascending dose (SAD) Part 1 will be a sequential SAD design in adult participants with SLE. Up to 5 dose levels of AZD5492 are planned to be investigated. Depending on emerging data, up to 4 additional dose levels may be added at the discretion of the Sponsor.

The decision to open Part 2 will be made by the Safety Review Committee (SRC) based on the evaluation of all available data including safety, tolerability, PK, and PD from Part 1 and pertinent data arising from other ongoing studies with AZD5492 will also be considered, and the dose levels and dosing strategy for Part 2 will be confirmed.

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.

Part 2 - Step-up dosing (SUD) Part 2 will be a SUD design in adult participants who have SLE (and did not participate in Part 1), as well as adult participants with IIM or RA. In Part 2, participants will receive 2 dose administrations, 7 days apart. The first (priming) dose of the step-up regimen will be agreed by the SRC. The second (target) dose will be escalated, and a minimum of 3 target dose levels are planned to be investigated in Part 2.

Study Type

Interventional

Enrollment (Estimated)

72

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8S 4K1
        • Not yet recruiting
        • Research Site
    • Quebec
      • Sherbrooke, Quebec, Canada, J1G 2E8
        • Recruiting
        • Research Site
  • China
      • Beijing, China, 100730
        • Recruiting
        • Research Site
      • Shanghai, China, 200001
        • Recruiting
        • Research Site
      • Wuhan, China, 430022
        • Recruiting
        • Research Site
      • Zhengzhou, China, 450052
        • Not yet recruiting
        • Research Site
  • France
      • Bordeaux, France, 33000
        • Recruiting
        • Research Site
      • Montpellier, France, 34295
        • Recruiting
        • Research Site
      • Nancy, France, 54035
        • Recruiting
        • Research Site
      • Paris, France, 75013
        • Recruiting
        • Research Site
      • Strasbourg, France, 67098
        • Recruiting
        • Research Site
      • Toulouse, France, 31059
        • Recruiting
        • Research Site
  • Germany
      • Cologne, Germany, 50937
        • Recruiting
        • Research Site
      • Erlangen, Germany, 91054
        • Recruiting
        • Research Site
      • Magdeburg, Germany, 39120
        • Not yet recruiting
        • Research Site
  • Hong Kong
      • Pok Fu Lam, Hong Kong, 999077
        • Not yet recruiting
        • Research Site
  • Japan
      • Bunkyō City, Japan, 113-8655
        • Recruiting
        • Research Site
      • Kita-gun, Japan, 761-0793
        • Recruiting
        • Research Site
      • Kitakyushu-shi, Japan, 807-8555
        • Recruiting
        • Research Site
      • Kyoto, Japan, 606-8501
        • Recruiting
        • Research Site
      • Nagasaki, Japan, 852-8501
        • Recruiting
        • Research Site
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Recruiting
        • Research Site
      • Leiden, Netherlands, 2333
        • Withdrawn
        • Research Site
  • Spain
      • Mérida, Spain, 06800
        • Recruiting
        • Research Site
      • Seville, Spain, 41010
        • Recruiting
        • Research Site
      • Valladolid, Spain, 47012
        • Recruiting
        • Research Site
  • United Kingdom
      • Glasgow, United Kingdom, G31 2ER
        • Recruiting
        • Research Site
      • London, United Kingdom, SE5 9RS
        • Recruiting
        • Research Site
      • London, United Kingdom, WC1E 6JF
        • Recruiting
        • Research Site
      • Southampton, United Kingdom, SO16 6YD
        • Recruiting
        • Research Site
  • United States
    • Alabama
      • Anniston, Alabama, United States, 36207
        • Recruiting
        • Research Site
      • Birmingham, Alabama, United States, 35233
        • Withdrawn
        • Research Site
    • California
      • La Jolla, California, United States, 92037
        • Not yet recruiting
        • Research Site
      • Sacramento, California, United States, 95817
        • Not yet recruiting
        • Research Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • Research Site
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Not yet recruiting
        • Research Site
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Not yet recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1: Single Ascending Dose with AZD5492
Participants will receive AZD5492 at an assigned dose as subcutaneous (SC) injection on Day 1.
Drug: AZD5492
IMP: subcutaneous.
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.
Drug: AZD5492
IMP: subcutaneous.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety evaluation of AZD5492: Frequency of dose limiting toxicities (DLTs).
Time Frame: Day 1 to end of the study (up to 52 weeks)
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
Time Frame: Day 1 to end of the study (up to 52 weeks)
Number and percentage of participants with SAEs leading to death.
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
Number and percentage of participants with abnormal ECG.
From Day 1 up to Day 180
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)
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.
Time Frame: Day 1 to end of the study (up to 52 weeks)
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: Number of participants with treatment-emergent adverse events by grade.
Time Frame: Day 1 to end of the study (up to 52 weeks)
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.
Time Frame: Day 1 to end of the study (up to 52 weeks)
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.
Time Frame: Day 1 to end of the study (up to 52 weeks)
Number and percentage of participants with treatment-related clinical laboratory abnormalities.
Day 1 to end of the study (up to 52 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute counts at Day 180 in blood CD19+ B-cells.
Time Frame: Day 180
Absolute counts at Day 180 in blood CD19+ B-cells.
Day 180
Serum Pharmacokinetics (PK) parameters of AZD5492 (Cmax)
Time Frame: From Day 1 through Day 60
Maximum observed serum drug concentration (Cmax) (μg/mL)
From Day 1 through Day 60
Serum Pharmacokinetics (PK) parameters of AZD5492 (AUC)
Time Frame: From Day 1 through Day 60
Area under the serum concentration-time curve (AUC) (μg/mL*h)
From Day 1 through Day 60
Serum Pharmacokinetics (PK) parameters of AZD5492 (t1/2λz)
Time Frame: From Day 1 through Day 60
Terminal elimination half-life (t1/2λz) (In hours)
From Day 1 through Day 60
Serum Pharmacokinetics (PK) parameters of AZD5492 (AUClast)
Time Frame: From Day 1 through Day 60
Area under the serum concentration time curve from time zero to the time of last quantifiable analyte concentration (AUClast) (nmol*h/L)
From Day 1 through Day 60
Incidence of ADAs to AZD5492 measured in serum.
Time Frame: From Day 1 through Day 180
Incidence of ADAs to AZD5492 measured in serum.
From Day 1 through Day 180

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Collaborators

Fortrea

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2025

Primary Completion (Estimated)

May 5, 2027

Study Completion (Estimated)

September 15, 2027

Study Registration Dates

First Submitted

March 13, 2025

First Submitted That Met QC Criteria

April 7, 2025

First Posted (Actual)

April 8, 2025

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 25, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D9961C00001
  • 2024-519015-34-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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