AZD5492 for Lupus and Myositis

(TITAN Trial)

Recruiting at 31 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must be taking: Immunosuppressive drugs

Must not be taking: B-cell depleting therapy

Disqualifiers: Severe SLE, APS, ILD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD5492 for individuals with lupus (SLE) or myositis (IIM), autoimmune conditions where the body's defense system attacks its own tissues. The trial aims to determine the safety of AZD5492 and how well participants tolerate it when administered as an injection under the skin. The trial consists of two parts: one with a single dose and another with two doses, based on safety data. Individuals with moderate to severe lupus or myositis who have not responded well to other treatments may be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how AZD5492 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications. However, you must be on a stable dose of certain medications like prednisolone, methotrexate, or mycophenolate mofetil for a specific period before joining the study.

Is there any evidence suggesting that AZD5492 is likely to be safe for humans?

Research has shown that AZD5492 is being tested for safety in people with lupus and myositis. As this treatment is in the early stages of testing, detailed safety information is still being gathered. Early trials aim to determine the treatment's safety and how well participants tolerate it.

Researchers closely monitor participants for any side effects or negative reactions. This vigilance ensures that any major safety issues are identified during the trial. Although specific safety details for AZD5492 are not yet available, the trial's focus on safety and participant tolerance highlights these as top priorities. Participants undergo frequent checks, with regular visits over several months to ensure their safety.

In summary, while detailed safety information for AZD5492 is still being collected, the trial prioritizes the safety and well-being of its participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus and myositis?

Unlike the standard treatments for lupus and myositis, which often include immunosuppressants and corticosteroids, AZD5492 is unique because it is specifically designed to be administered as a subcutaneous injection. This method could offer a more targeted delivery of treatment, potentially leading to fewer side effects compared to oral medications. Additionally, AZD5492's dosing approach, which includes a step-up method based on safety data, allows for personalized treatment adjustments, enhancing its potential effectiveness. Researchers are excited about these features as they could provide a more efficient and safer treatment option for patients suffering from these conditions.

What evidence suggests that AZD5492 might be an effective treatment for lupus and myositis?

Research is investigating AZD5492 as a potential treatment for autoimmune diseases such as systemic lupus erythematosus (SLE) and idiopathic inflammatory myopathies (IIM). In these conditions, the immune system mistakenly attacks the body. AZD5492 aims to reduce inflammation and control the disease by targeting specific parts of the immune system. Although solid proof of AZD5492's effectiveness in humans is not yet available, it is designed to help manage symptoms by calming the overactive immune response in these diseases. Early signs from similar treatments have been encouraging, but further studies are needed to confirm its benefits. Participants in this trial will receive AZD5492 in various dosing regimens to evaluate its safety and effectiveness. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with systemic lupus erythematosus (SLE) or idiopathic inflammatory myopathies (IIM). Participants must be able to attend multiple study visits over a minimum of 180 days, with possible follow-ups up to 12 months. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

I have been diagnosed with lupus according to the 2019 criteria.

My lupus is active and severe, with a score of 4 or higher.

Positive for ≥ 1 disease-specific autoantibody performed by the central laboratory at screening

Exclusion Criteria

I have had severe brain or nerve issues due to lupus.

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. Participants with clinically evident APS which is adequately controlled by anticoagulants or aspirin for at least 12 weeks can be recruited into the study; Rapidly progressive and/or severe ILD or ILD that requires oxygen supplementation/therapy (of any type); Inclusion Body Myositis or cancer associated myositis

Infections: Any clinical suspicion or diagnosis of active infection at screening; Opportunistic infection that meets criteria to be an SAE within 3 years; Clinically significant chronic infection (eg, osteomyelitis, bronchiectasis) with treatment completed less than 2 months prior to signing the ICF (except for chronic nail infections, which are allowed); Any history of infection requiring: Hospitalisation within the previous two months; Treatment with IV anti-infectives with treatment completed less than 4 weeks prior to signing the ICF; Oral anti-infectives within 2 weeks prior to signing the ICF; History of recurrent infection requiring hospitalisation or IV antibiotics eg 3 or more of the same type of infection, including systemic fungal infections, over the previous 52 weeks; Participants with HIV infection (confirmed by central laboratory at screening); Participants with active EBV or CMV; 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 defined as: HCV IgM Ab positive; Detectable HCV RNA; Positive result for HCV IgG Ab is acceptable in the following circumstances: HCV RNA is undetectable >12 weeks after completion of curative antiviral treatment for HCV; HCV RNA is undetectable on two occasions at least 12 weeks apart following resolution of HCV infection if not treated; Participants with positive COVID-19 PCR. For participants with a positive COVID-19 reverse transcription PCR at screening, rescreening will be conducted not earlier than 6 weeks after the positive result. Only one rescreening is allowed; Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection; CNS pathology including but limited to the following: CNS vasculitis, severe brain injury, dementia, Parkinson's disease, neurodegenerative diseases, cerebellar disease, stroke, seizure disorder/epilepsy, PML, severe uncontrolled mental illness, psychosis, CNS involvement of autoimmune diseases; 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 signing the ICF. If therapy was administered ≥3 months ago, exclude if absolute B-cell less than the lower limit of normal; Prednisolone (or equivalent) > 20 mg within 2 months of signing the ICF.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 weeks

1 visit (in-person)

Treatment Part 1

Participants receive a single ascending dose of AZD5492

26 weeks

Visits on Days 1-4, 8, 15, 22, 30, 60, 90, 120, 150, and 180

Treatment Part 2

Participants receive step-up dosing of AZD5492 with two administrations

26 weeks

Visits on Days 1-4, 8-11, 15, 22, 29, 43, 60, 90, 120, 150, and 180

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 52 weeks

Additional follow-up visits may be required

What Are the Treatments Tested in This Trial?

Interventions

• AZD5492

Trial Overview The trial is testing AZD5492, given as a subcutaneous injection, for safety and effectiveness in treating SLE or IIM. Part 1 involves one dose; Part 2 involves two doses. The drug's effects on the body will be monitored through regular visits over six months.

How Is the Trial Designed?

Group I: Part 2: Step-Up Dosing with AZD5492 Experimental Treatment 1 Intervention

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.

Group II: Part 1: Single Ascending Dose with AZD5492 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

Published Research Related to This Trial

In a real-world study of 501 patients with systemic lupus erythematosus (SLE) receiving belimumab for up to 12 months, 31.1% achieved disease control defined as a SELENA-SLEDAI score of ≤2, indicating significant improvement in disease activity.

Glucocorticoid use was notably reduced from a median of 20 mg/day at baseline to 5 mg/day at 12 months, demonstrating that belimumab treatment can help lower the need for these steroids, although no patients achieved complete remission (SELENA-SLEDAI score of 0) during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating disease control following belimumab treatment in patients with SLE enrolled in the US OBSErve study. Hunnicutt, JN., Fairburn-Beech, J., Georgiou, ME., et al.[2023]

In a study of systemic lupus erythematosus (SLE) patients, the probability of reaching a lupus low disease activity state (LLDAS) within one year was 52% for Caucasians, but only 36% for African Americans and 33% for those with renal involvement, highlighting disparities in treatment outcomes.

Factors such as African American ethnicity, high baseline prednisone use, and renal activity were significant predictors of a longer time to achieve LLDAS, indicating the need for tailored approaches in managing SLE, especially for African American patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time to Lupus Low Disease Activity State in the Hopkins Lupus Cohort: Role of African American Ethnicity. Babaoğlu, H., Li, J., Goldman, D., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06916806

NCT06916806 | A Study to Investigate Safety, Tolerability ... 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.

2. withpower.com withpower.com/trial/phase-1-lupus-erythematosus-systemic-3-2025-30c02

AZD5492 for Lupus and Myositis (TITAN Trial) In a real-world study of 501 patients with systemic lupus erythematosus (SLE) receiving belimumab for up to 12 months, 31.1% achieved disease control defined as ...

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9961C00001

A Study to Investigate Safety, Tolerability ... 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.

4. trial.medpath.com trial.medpath.com/drug/fe45027ea19abdde/azd-5492

AZD-5492 - MedPath A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD5492 in Adult Participants With Systemic Lupus ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06916806?term=AREA%5BConditionSearch%5D(Acquired%20idiopathic%20inflammatory%20myopathy%20OR%20%22idiopathic%20inflammatory%20myopathies%22%20OR%20%22%20idiopathic%20inflammatory%20myositis%22%20OR%20%22%20IIm%22%20OR%20%22%20IMM%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=10

NCT06916806 | A Study to Investigate Safety, Tolerability ... 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.

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06916806/a-study-to-investigate-safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-azd5492-in-adult-participants-with-systemic-lupus-erythematosus-or-idiopathic-inflammatory-myopathies

A Study to Investigate Safety, Tolerability, Pharmacokinetics, and ... 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.

7. trialx.com trialx.com/clinical-trials/listings/311576/a-study-to-investigate-safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-azd5492-in-adult-participants-with-systemic-lupus-erythematosus-or-idiopathic-inflammatory-myopathies/?&radius=10&place=Putzu&user_country=Taiwan

A Study to Investigate Safety, Tolerability ... The purpose of this study is to measure the safety, tolerability, PK, and PD of AZD5492 administered subcutaneously in adult participants with ...