Systemic Lupus ErythematosusPhase 1TITANNCT06916806
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.
A Phase 1 study testing AZD5492 in people with Systemic Lupus Erythematosus and Idiopathic Inflammatory Myopathies, run by AstraZeneca at 38 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Systemic Lupus Erythematosus, Idiopathic Inflammatory Myopathies, Rheumatoid Arthritis
- What is being tested?
- AZD5492
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 38 sitesin 10 countries
- Study dates
- 1 May 2025to 15 Sep 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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:
- 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.
- 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:
- 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.
Who cannot join
- 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).
- Inclusion Body Myositis or cancer associated myositis.
- Active severe, unstable or history of neuropsychiatric SLE.
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- 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.
- Significant CNS pathology.
- 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 and contacts
38 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
38 sites in 10 countries
United States7 sites, 6 recruiting
- Recruiting
Research Site
Anniston, Alabama, 36207
- Withdrawn
Research Site
Birmingham, Alabama, 35233
- Not yet recruiting
Research Site
Chapel Hill, North Carolina, 27599
- Recruiting
Research Site
Iowa City, Iowa, 52242
- Recruiting
Research Site
La Jolla, California, 92037
- Not yet recruiting
Research Site
Omaha, Nebraska, 68198
- Not yet recruiting
Research Site
Sacramento, California, 95817
France7 sites, 7 recruiting
- Recruiting
Research Site
Bordeaux, 33000
- Recruiting
Research Site
Montpellier, 34295
- Recruiting
Research Site
Nancy, 54035
- Recruiting
Research Site
Paris, 75013
- Recruiting
Research Site
Paris, 75651
- Recruiting
Research Site
Strasbourg, 67098
- Recruiting
Research Site
Toulouse, 31059
Japan5 sites, 5 recruiting
- Recruiting
Research Site
Bunkyō City, 113-8655
- Recruiting
Research Site
Kita-gun, 761-0793
- Recruiting
Research Site
Kitakyushu-shi, 807-8555
- Recruiting
Research Site
Kyoto, 606-8501
- Recruiting
Research Site
Nagasaki, 852-8501
China4 sites, 4 recruiting
- Recruiting
Research Site
Beijing, 100730
- Recruiting
Research Site
Shanghai, 200001
- Recruiting
Research Site
Wuhan, 430022
- Recruiting
Research Site
Zhengzhou, 450052
United Kingdom4 sites, 4 recruiting
- Recruiting
Research Site
Glasgow, G31 2ER
- Recruiting
Research Site
London, SE5 9RS
- Recruiting
Research Site
London, WC1E 6JF
- Recruiting
Research Site
Southampton, SO16 6YD
Germany3 sites, 3 recruiting
- Recruiting
Research Site
Cologne, 50937
- Recruiting
Research Site
Erlangen, 91054
- Recruiting
Research Site
Magdeburg, 39120
Spain3 sites, 3 recruiting
- Recruiting
Research Site
Mérida, 06800
- Recruiting
Research Site
Seville, 41010
- Recruiting
Research Site
Valladolid, 47012
Canada2 sites, 2 recruiting
- Recruiting
Research Site
Hamilton, Ontario, L8S 4K1
- Recruiting
Research Site
Sherbrooke, Quebec, J1G 2E8
Netherlands2 sites, 1 recruiting
- Recruiting
Research Site
Amsterdam, 1105 AZ
- Withdrawn
Research Site
Leiden, 2333
About this study
Official title: 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), twice (Part 2a), or three times (Part 2b).
Read the 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 with SLE, IIM, or RA and consists of:
Part 2a (sSUD): 2 dose administrations, 7 days apart (priming dose followed by target dose).
Part 2b (dSUD): 3 dose administrations, 7 days apart (2 priming doses followed by a target dose) to further mitigate CRS and ICANS risk.
Participants who complete the study may be eligible for re-enrolment and re-treatment according to protocol-defined criteria.
- Being tested
- AZD5492
- Keywords
- Lupus, Inflammatory Myopathy, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases, Muscular Diseases, Myositis, Dermatomyositis, Polymyositis, Arthritis
- Medical subject headings
- Lupus Erythematosus, Systemic, Myositis, Arthritis, Rheumatoid, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases, Muscular Diseases, Dermatomyositis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5492Drug
IMP: subcutaneous.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Single Ascending Dose with AZD5492 | Experimental | Participants will receive AZD5492 at an assigned dose as subcutaneous (SC) injection on Day 1. Receives: Drug: AZD5492 |
| Part 2: Step-Up Dosing with AZD5492 | Experimental | Participants will receive AZD5492 by SC as either:
* Part 2a (sSUD): a priming dose on Day 1 followed by a target dose on Day 8; or
* Part 2b (dSUD): a priming dose on Day 1, a second priming dose on Day 8, and a target dose on Day 15. Receives: Drug: AZD5492 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events.
Number and percentage of participants with AEs, AESIs, and SAEs
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Day 1 up to Day 180
Secondary outcomes (6)
Serum Pharmacokinetics (PK) parameters of AZD5492 (Cmax)
Maximum observed serum drug concentration (Cmax) (μg/mL)
Measured: From Day 1 through Day 60
Serum Pharmacokinetics (PK) parameters of AZD5492 (AUC)
Area under the serum concentration-time curve (AUC) (μg/mL*h)
Measured: From Day 1 through Day 60
Serum Pharmacokinetics (PK) parameters of AZD5492 (t1/2λz)
Terminal elimination half-life (t1/2λz) (In hours)
Measured: From Day 1 through Day 60
Serum Pharmacokinetics (PK) parameters of AZD5492 (AUClast)
Area under the serum concentration time curve from time zero to the time of last quantifiable analyte concentration (AUClast) (nmol*h/L)
Measured: From Day 1 through Day 60
Incidence of ADAs to AZD5492 measured in serum.
Incidence of ADAs to AZD5492 measured in serum.
Measured: From Day 1 through Day 180
Absolute counts at Day 180 in blood CD19+ B-cells.
Absolute counts at Day 180 in blood CD19+ B-cells.
Measured: Day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2025
- Study start1 May 2025
- Primary completion5 May 2027 (estimated)
- Study completion15 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Open-Label, single-arm treatment study.
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Fortrea
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06916806
- Sponsor's protocol ID
- D9961C00001
- Other IDs
- 2024-519015-34-00
- Acronym
- TITAN
- Status last verified
- Oct 2026
- First submitted
- 13 Mar 2025
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.