Summary

Eligibility
for people ages 18-75 (full criteria)
Location
at Irvine, California and other locations
Dates
study started
completion around
Principal Investigator
by Tahseen Mozaffar
Headshot of Tahseen Mozaffar
Tahseen Mozaffar

Description

Summary

The primary efficacy objective:

To evaluate the effect of daxdilimab compared with placebo in reducing disease activity at Week 24.

The secondary efficacy objectives include:

  1. To evaluate the effect of daxdilimab compared with placebo in reducing disease activity at Week 24.
  2. To evaluate the effect of daxdilimab compared with placebo on skin symptoms at Week 24.
  3. To evaluate the effect of daxdilimab on decreasing the use of corticosteroid at Week 24.

Other secondary objectives include:

  1. To characterize the pharmacokinetics (PK) and immunogenicity of daxdilimab in participants.
  2. To evaluate the safety and tolerability of daxdilimab in participants.

Official Title

A Phase 2, Randomized, Double-blind, Placebo-controlled, Efficacy and Safety Study of Daxdilimab Subcutaneous Injection in Adult Participants With Inadequately Controlled Dermatomyositis or Anti-synthetase Inflammatory Myositis.

Details

The study will enroll 96 participants with 2 idiopathic inflammatory myositis populations:

  • Population 1 or dermatomyositis (DM): participants with DM with definite or probable myositis according to the American College of Rheumatology/European League Against Rheumatism 2017 (ACR/EULAR 2017) criteria and a DM rash.
  • Population 2 or anti-synthetase inflammatory myositis (ASIM): participants with ASIM with definite or probable myositis according to ACR/EULAR 2017 criteria and a positive ASIM associated antibody.

Participants will be randomized by population in a 1:1 ratio and receive investigational product (IP) daxdilimab or placebo by subcutaneous injection.

The estimated total study duration will be up to 60 weeks.

Keywords

Idiopathic Inflammatory Myositis, Anti-synthetase syndrome, Myositis, Polymyositis, Dermatomyositis, Daxdilimab

Eligibility

You can join if…

Open to people ages 18-75

  1. Adult men or women 18 and ≤ 75 years of age at the time of signing the informed consent (ICF).
  2. A diagnosis of definite or probable myositis according to American College of

    Rheumatology/European League Against Rheumatism 2017 (ACR/EULAR 2017) criteria:

    1. Population 1: DM
      • Diagnosis of DM with DM rash current or historical, or
    2. Population 2: ASIM
      • Anti-histidyl tRNA synthetase-(Anti-Jo-1) antibodies must be positive during screening by central laboratory testing, or
      • One of following antibodies must be positive by historical testing: directed against anti-alanyl- (anti-PL-12), anti-threonyl-(anti PL-7), anti-asparaginyl-(anti-KS), anti-glycyl-(anti-EJ), anti-isoleucyl-(anti-OJ), anti-phenylalanyl-transfer RNA synthetase-(anti-ZO), anti-tyrosil-YRS(HA).
  3. Currently active myositis with all the following (a, b, and c) during screening:
    1. Manual Muscle Testing (MMT 8) score < 142
    2. At least 2 other abnormal core set measures (CSM) from the following list:
      • Patient global disease activity (PtGDA) ≥ 2cm in a 10 cm visual analog scale (VAS)
      • Physician's Global Disease Activity (PhGDA) ≥ 2 cm in a 10 cm VAS
      • Extramuscular activity ≥ 2cm in a 10 cm VAS
      • At least one muscle enzyme 1.5 times upper limit of normal (ULN)
      • Health assessment questionnaire-disability index (HAQ-DI) ≥ 0.5
    3. Global muscle damage score ≤ 5 on a 10 cm VAS on the myositis damage index (MDI).
  4. Participants should be on stable standard of care therapy if tolerated; if they are not able to tolerate it or have failed standard of care, medications should have a washed out period.
  5. Participants should be willing to taper corticosteroid dose per protocol when stable or improving.

You CAN'T join if...

  1. Any condition that, in the opinion of the investigator or sponsor, would interfere with the evaluation of investigational product (IP) or interpretation of participant safety or study results.
  2. Weight > 160 kg (352 pounds) at screening.
  3. Breastfeeding or pregnant women or women who intend to become pregnant anytime from signing the ICF through 6 months after receiving the last dose of IP.
  4. History of clinically meaningful cardiac disease including unstable angina, myocardial infarction, congestive heart failure within 6 months prior to randomization; arrhythmia requiring active therapy, except for clinically insignificant extra systoles, or minor conduction abnormalities; or presence of clinically meaningful abnormality on electrocardiogram (ECG) if, in the opinion of the Investigator, it would increase the risk of study participation.
  5. History of cancer within the past 5 years, except as follows:
    • In situ carcinoma of the cervix treated with apparent success with curative therapy > 12 months prior to screening, or
    • Cutaneous basal cell or squamous cell carcinoma treated with curative therapy.
  6. Any underlying condition that in the opinion of the Investigator significantly predisposes the participant to infection.
  7. Known history of a primary immunodeficiency or an underlying condition, such as known human immunodeficiency virus (HIV) infection, or a positive result for HIV infection per central laboratory.
  8. Confirmed positive test for hepatitis B virus serology as defined in the protocol.
  9. Active tuberculosis (TB), or a positive interferon gamma (IFN-γ) release assay (IGRA) test at screening, unless documented history of appropriate treatment for active or latent TB according to local guidelines.

    10. Any severe herpes virus family infection (including Epstein-Barr virus,

    cytomegalovirus [CMV]) at any time prior to randomization.

    11. Opportunistic infection requiring hospitalization or parenteral antimicrobial

    treatment within 2 years prior to randomization.

    12. Significant organ system involvement or myositis damage (global muscle damage score >

    5 on a 10cm VAS scale on the MDI) that poses risks in the study or impedes assessments.

    13. Diagnosis of immune-mediated necrotizing myopathy (IMNM) [(positive

    3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGR), anti-signal recognition particle (anti- SRP), or antibody negative)], inclusion body myositis (IBM) (including positive anti-cytosolic 5'-nucleotidase 1A (anti cN1A), or drug-induced myositis.

    14. Current musculoskeletal, joint, or inflammatory disease, including significant joint

    contractures or calcinosis that in the opinion of the investigator, could interfere with the muscle strength assessments and confound the disease activity assessments.

    15. Wheelchair bound participants. 16. Current inflammatory skin disease other than DM or ASIM that, in the opinion of the

    investigator, could interfere with the inflammatory skin assessments or confound the disease activity assessments.

    17. Severe interstitial lung disease where respiratory symptoms limit participant function

    or progressive pulmonary fibrosis.

    18. Myositis in overlap with another connective tissue disease that precludes the accurate

    assessment of a treatment response (for example, difficulty in assessing muscle strength in a scleroderma patient with associated myositis).

Locations

  • University of California Irvine accepting new patients
    Irvine California 92617-3058 United States
  • Advanced Research Center accepting new patients
    Anaheim California 92805-5854 United States

Lead Scientist at UC Irvine

  • Tahseen Mozaffar
    Clinical Professor, Neurology, School of Medicine. Authored (or co-authored) 145 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Horizon Therapeutics Ireland DAC
ID
NCT05669014
Phase
Phase 2 Idiopathic Inflammatory Myositis Research Study
Study Type
Interventional
Participants
Expecting 96 study participants
Last Updated