Polymyositis, Dermatomyositis
Conditions
Keywords
Polymyositis, Dermatomyositis, anifrolumab
Brief summary
The purpose of this multicenter, randomized, placebo-controlled and double-blind study is to evaluate the efficacy and safety of subcutaneous anifrolumab compared with placebo on the overall disease activity in participants with moderate to severe Idiopathic Inflammatory Myopathies (IIM) \[polymyositis (PM) or dermatomyositis (DM)\] while receiving standard of care (SoC) treatment.
Interventions
COMBINATION_PRODUCTAnifrolumab (blinded)
Anifrolumab treatment delivered subcutaneously, once weekly for 52 weeks
OTHERPlacebo
Matched placebo delivered subcutaneously, once weekly for 52 weeks
COMBINATION_PRODUCTAnifrolumab (unblinded, open label)
At Week 52, all study participants on anifrolumab or placebo will receive open label anifrolumab once weekly for an additional 52 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Capable of giving informed consent. Inclusion Criteria: 1. 18 - 75 years old 2. Body weight ≥40 kg 3. Must have "probable" or "definite" diagnosis of PM or DM according to the 2017 ACR/EULAR classification criteria for adult myositis. 4. Moderate or severe disease activity per core set measurements. 5. Currently receiving oral prednisone or other polymyositis or dermatomyositis treatments at a stable dose. 6. No history of active tuberculosis or severe COVID-19. 7. Male and female participants must follow contraception guidelines.
Exclusion criteria
1. Participants with documented inclusion body myositis (IBM), immune mediation necrotizing myositis (IMNM), juvenile myositis (if diagnosed within 10 years prior to signing the ICF), drug-induced myositis, cancer associated myositis, amyopathic DM, and non inflammatory myopathies (eg, muscular dystrophies). 2. PM and DM patients at a high risk of malignancy. 3. Participants with rapidly progressive interstitial lung disease. 4. Participants with severe muscle damage or permanent weakness due to non-PM or non-DM conditions (i.e. stroke) as per the investigator's opinion. 5. Any history of severe case of herpes zoster infection 6. History of cancer (except adequately treated basal cell carcinoma or cervical cancer in-situ), immunodeficiency, HIV, HBV, active HCV . 7. Any clinical cytomegalovirus or Epstein-Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF. 8. Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years prior to randomization. 9. Recent non-opportunistic infection requiring hospitalization or anti-infective treatment. 10. Recent or concurrent enrollment in another clinical study with an investigational product. 11. Lactating, breastfeeding, or pregnant females or females who intend to become pregnant or begin breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Improvement Score (TIS) ≥ 40 response | 52 week | Participants who have at least moderate improvement in disease activity TIS ≥ 40 and has not met "confirmed deterioration" criteria at 2 consecutive visits |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Manual Muscle Testing 8 (MMT-8) (CSM) | 52 week | MMT-8 (CSM) change from baseline at Week 52. |
| Oral corticosteroid dose ≤ 7.5 mg/day | 52 week | Participants who achieve oral corticosteroid dose ≤ 7.5 mg/day at Week 52. |
| Moderate improvement in disease activity in participants with polymyositis (PM) | 52 week | Participants with PM who have at least moderate improvement in disease activity (TIS ≥ 40) at Week 52. |
| Moderate improvement in disease activity in dermatomyositis (DM) participants. | 52 week | Participants with DM who have at least moderate improvement in disease activity (TIS ≥ 40). |
| Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) | 8 week | CDASI activity change from baseline at Week 8 in DM participants only. |
| Manual Muscle Testing 8 (MMT-8) in PM participants | 52 Week | MMT-8 change from baseline at Week 52 in PM participants only. |
| Manual Muscle Testing 8 (MMT-8) in DM participants | 52 Week | MMT-8 change from baseline at Week 52 in DM participants only. |
| Core Set Measures (CSMs) | 52 week | Change from baseline at Week 52 in CSMs: * PGA * PtGA * Muscle enzymes * MDAAT extra-muscular disease activity * HAQ-DI |
| Oral corticosteroid dose ≤ 7.5 mg/day in PM participants | 52 week | PM participants who achieve oral corticosteroid dose ≤ 7.5 mg/day at Week 52 |
| Oral corticosteroid dose ≤ 7.5 mg/day in DM participants | 52 week | DM participants who achieve oral corticosteroid dose ≤ 7.5 mg/day at Week 52. |
| Cutaneous Dermatomyositis Activity Investigator Global Assessment (CDA-IGA) | 8, 24, & 52 week | DM Participants with CDA-IGA ≥ 2 at baseline who achieve: * CDA-IGA score ≤ 1 at Week 8 (yes/no) * CDA-IGA score ≤ 1 at Week 24 (yes/no) * CDA-IGA score ≤ 1 at Week 52 (yes/no) |
| 5-D itch | 8, 24, & 52 week | DM participants with CDASI activity \> 14 at baseline only: * 5-D itch change from baseline at Week 8 * 5-D itch change from baseline at Week 24 * 5-D itch change from baseline at Week 52 |
| Total Improvement Score (TIS) ≥ 20 Response | 8 week | Participants who have at least minimal improvement in disease activity TIS ≥ 20 at Week 8 and has not met "confirmed deterioration" criteria at 2 consecutive visits up and including Week 8 |
| Total Improvement Score ≥ 60 Response | 52 week | Participants who have major improvement in disease activity TIS ≥ 60 at week 52 and has not met "confirmed deterioration" criteria at 2 consecutive visits up to and including Week 52 |
| Cumulative Corticosteroid Use | 24, 52 week | * Cumulative corticosteroids use as determined by the normalized standardized AUC from baseline up to and including Week 24 * Cumulative corticosteroids use as determined by the normalized standardized AUC from baseline up to and including Week 52 |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Mexico, Netherlands, Poland, Puerto Rico, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed