Recruiting
Phase 1
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.
Condition(s) studied
Systemic Lupus ErythematosusIdiopathic Inflammatory MyopathiesRheumatoid Arthritis
Investigational drug(s) / intervention(s)
AZD5492
AZD5492: IMP: subcutaneous.
Study 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), twice (Part 2a), or three times (Part 2b).
Eligibility
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.
Primary outcome measure(s)
- Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events. — Day 1 to end of the study (up to 52 weeks)
Number and percentage of participants with AEs, AESIs, and SAEs
- Safety evaluation of AZD5492: Number of participants with related treatment-emergent adverse events. — 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
- Safety evaluation of AZD5492: Frequency of dose limiting toxicities (DLTs). — 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.
- Safety evaluation of AZD5492: Number of SAEs leading to death — Day 1 to end of the study (up to 52 weeks)
Number and percentage of participants with SAEs leading to death.
- Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events by grade. — 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.
- Tolerability evaluation of AZD5492: Number of participants with treatment-emergent vital signs abnormalities. — Day 1 to end of the study (up to 52 weeks)
Number and percentage of participants with treatment-related vital signs abnormalities.
- Tolerability evaluation of AZD5492: Number of participants with treatment-emergent clinical laboratory abnormalities. — Day 1 to end of the study (up to 52 weeks)
Number and percentage of participants with treatment-related clinical laboratory abnormalities.
- Tolerability evaluation of AZD5492: Number of participants with abnormal ECG. — From Day 1 up to Day 180
Number and percentage of participants with abnormal ECG.
Trial sites (37)
| Facility | City | Region | Status |
| Research Site |
Anniston |
Alabama |
Recruiting |
| Research Site |
Birmingham |
Alabama |
Withdrawn |
| Research Site |
La Jolla |
California |
Not Yet Recruiting |
| Research Site |
Sacramento |
California |
Not Yet Recruiting |
| Research Site |
Iowa City |
Iowa |
Recruiting |
| Research Site |
Omaha |
Nebraska |
Not Yet Recruiting |
| Research Site |
Chapel Hill |
North Carolina |
Not Yet Recruiting |
| Research Site |
Hamilton |
Ontario |
Not Yet Recruiting |
| Research Site |
Sherbrooke |
Quebec |
Recruiting |
| Research Site |
Beijing |
China |
Recruiting |
| Research Site |
Shanghai |
China |
Recruiting |
| Research Site |
Wuhan |
China |
Recruiting |
| Research Site |
Zhengzhou |
China |
Not Yet Recruiting |
| Research Site |
Bordeaux |
France |
Recruiting |
| Research Site |
Montpellier |
France |
Recruiting |
| Research Site |
Nancy |
France |
Recruiting |
| Research Site |
Paris |
France |
Recruiting |
| Research Site |
Strasbourg |
France |
Recruiting |
| Research Site |
Toulouse |
France |
Recruiting |
| Research Site |
Cologne |
Germany |
Recruiting |
| Research Site |
Erlangen |
Germany |
Recruiting |
| Research Site |
Magdeburg |
Germany |
Not Yet Recruiting |
| Research Site |
Pok Fu Lam |
Hong Kong |
Recruiting |
| Research Site |
Bunkyō City |
Japan |
Recruiting |
| Research Site |
Kita-gun |
Japan |
Recruiting |
| Research Site |
Kitakyushu-shi |
Japan |
Recruiting |
| Research Site |
Kyoto |
Japan |
Recruiting |
| Research Site |
Nagasaki |
Japan |
Recruiting |
| Research Site |
Amsterdam |
Netherlands |
Recruiting |
| Research Site |
Leiden |
Netherlands |
Withdrawn |
| Research Site |
Mérida |
Spain |
Recruiting |
| Research Site |
Seville |
Spain |
Recruiting |
| Research Site |
Valladolid |
Spain |
Recruiting |
| Research Site |
Glasgow |
United Kingdom |
Recruiting |
| Research Site |
London |
United Kingdom |
Recruiting |
| Research Site |
London |
United Kingdom |
Recruiting |
| Research Site |
Southampton |
United Kingdom |
Recruiting |