ClinicalTrials.gov record NCT06916806
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.
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
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This open-label Phase 1 study evaluates the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD5492 given by subcutaneous injection in adults with systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies (IIM), or rheumatoid arthritis (RA). The study has two parts: Part 1 is single ascending doses and Part 2 uses step-up dosing (two or three injections). Participants are followed for at least 179 days after dosing, with additional follow-up possible up to about 12 months; some who complete the study may be eligible for re-enrolment.
What it is studying. The study is testing the safety and tolerability of AZD5492 and measuring how the drug behaves in the body (pharmacokinetics) and its biological effects (pharmacodynamics) using single and step-up subcutaneous dosing schedules.
What the researchers hope to learn. Scientific goals: assess safety and tolerability of AZD5492; characterize pharmacokinetics and pharmacodynamics across doses and schedules; measure anti-drug antibodies and CD19+ B-cell counts; and generate data to inform dose selection and dosing strategies, including step-up dosing intended to mitigate risks such as cytokine release syndrome (CRS) and immune effector neurotoxicity (ICANS).
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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).
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- AZD5492
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- 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.
Exclusion criteria
- 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.
- 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.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
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.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
After a screening period (up to 42 days), participants receive one or more subcutaneous injections of AZD5492: a single dose in Part 1, two doses 7 days apart in Part 2a (priming then target), or three doses 7 days apart in Part 2b (two priming doses then target). Participants will have clinic visits for safety monitoring and follow‑up, including blood samples to measure drug levels (PK), anti‑drug antibodies (ADAs), and immune cell counts (for example CD19+ B cells), as well as vital signs and ECGs at specified times. Follow‑up lasts at least 179 days after dosing (the study notes a minimum of 180 days in addition to screening) and some participants may have additional visits up to about 12 months from study start. Participants who complete the study may be eligible for re‑enrolment and re‑treatment according to the protocol.
How the study is structured. Open-label, non-randomized Phase I study with sequential dose escalation. Part 1 (single ascending dose) enrolls adults with SLE and will investigate multiple dose levels. Part 2 (step-up dosing) enrolls adults with SLE, IIM, or RA and includes a two-dose schedule (priming dose then target dose, 7 days apart) and a three-dose schedule (two priming doses then target dose, each 7 days apart). Participants receive one (Part 1), two (Part 2a), or three (Part 2b) subcutaneous injections of AZD5492 and are followed for safety, PK, and PD (safety follow-up extends up to about 52 weeks per the protocol). There is no masking.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in Canada, China, France, Germany, Hong Kong, Japan, Netherlands, Spain, United Kingdom, United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on dermatomyositis
This trial is also listed on this site under polymyositis.
Important dates
- Study start
- May 1, 2025
- Primary completion
- May 5, 2027 (estimated)
- Study completion
- Sep 15, 2027 (estimated)
- Target enrollment
- 72 participants (estimated)
- Last updated on registry
- Sep 15, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- AstraZeneca
- Collaborators
- Fortrea
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- AstraZeneca Clinical Study Information Center 📞 1-877-240-9479 ✉ information.center@astrazeneca.com
Participating sites (37)
- Research SiteRecruiting
Anniston, Alabama, 36207 · United States
- Research SiteWithdrawn
Birmingham, Alabama, 35233 · United States
- Research SiteNot Yet Recruiting
La Jolla, California, 92037 · United States
- Research SiteNot Yet Recruiting
Sacramento, California, 95817 · United States
- Research SiteRecruiting
Iowa City, Iowa, 52242 · United States
- Research SiteNot Yet Recruiting
Omaha, Nebraska, 68198 · United States
- Research SiteNot Yet Recruiting
Chapel Hill, North Carolina, 27599 · United States
- Research SiteNot Yet Recruiting
Hamilton, Ontario, L8S 4K1 · Canada
- Research SiteRecruiting
Sherbrooke, Quebec, J1G 2E8 · Canada
- Research SiteRecruiting
Beijing, 100730 · China
Terms used on this page · explanations by MedicalUpdates.ai
- PK
- How the body absorbs, distributes, breaks down and removes a drug. It is studied by measuring drug levels or related substances at set times after a dose.
- screening period
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- corticosteroids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- × ULN
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- MRI
- A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- contraindicated
- A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
- FVC
- A breathing test that measures the total amount of air a person can blow out after a full breath in. It is often given as a percentage of what is expected for a person's age and size.
- DLCO
- A breathing test that measures how well the lungs pass oxygen from the air into the blood.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- open-label
- No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
- pharmacodynamics
- What a drug does to the body, for example how it changes a blood marker or a symptom, and how that relates to the dose.
- ascending dose
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- Sponsor
- The organisation or person that initiates the study and has authority over it. The sponsor may be a company, hospital, university, government agency or individual, and is not necessarily the organisation that funds the study.
- CRS
- A reaction in which the immune system releases a large amount of signalling proteins at once, causing fever and sometimes low blood pressure or breathing problems. It can occur after some immune therapies, such as CAR-T cells or bispecific antibodies.
- ICANS
- Nervous-system side effects, such as confusion or difficulty speaking, that can occur after some immune therapies. Usually temporary, but monitored closely.
- enrolment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
← Back to clinical trials