A Phase 2 proof of concept study to evaluate the efficacy and safety of daxdilimab in participants with dermatomyositis or anti-synthetase inflammatory myositis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Horizon Therapeutics Ireland Designated Activity Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

12 Sep 2023 → 2 Jul 2025

Decision date (initial)

2023-07-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Horizon Therapeutics Ireland DAC

External identifiers

EU CT number

2022-502810-10-00

ClinicalTrials.gov

NCT05669014

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Diagnosis, Efficacy, Pharmacodynamic, Safety, Pharmacogenetic, Dose response, Pharmacokinetic, Prophylaxis

The primary efficacy objective is to evaluate the effect of daxdilimab compared with placebo in reducing disease activity at Week 24.

Secondary objectives 1

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

Conditions and MedDRA coding

Dermatomyositis (DM) or anti-synthetase inflammatory myositis (ASIM)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. '- Adult men or women ≥ 18 and ≤ 75 years of age at the time of signing the ICF. - A diagnosis of definite or probable myositis according to ACR/EULAR 2017 criteria (A OR B): -A. Total aggregated score ≥ 5.5 without a muscle biopsy Note: Pathognomonic skin rash (heliotrope rash, Gottron’s papules and/or Gottron’s sign) is required if no muscle biopsy is available. -OR -B. Total aggregated score ≥ 6.7 with muscle biopsy Note: The local muscle biopsy report will be used in the ACR/EULAR 2017 criteria to determine participant eligibility. Submission of the historical biopsy sample (archived tissue block, physical slides, and/or digital pathology slides) or documentation of attempts to obtain results of historical biopsy is required for randomized participants. -AND (a or b) a. Population 1: DM • Diagnosis of DM with DM rash current or historical, -OR b. Population 2: ASIM • Anti-Jo-1 antibodies must be positive during Screening by central laboratory testing, or • One of following antibodies must be positive by historical testing: anti-PL-12,anti-PL-7, anti-KS, anti-EJ, anti-OJ, anti-ZO, anti-YRS(HA). Currently active myositis with all the following (a, b, and c) during Screening: a. MMT8 score < 142 b. At least 2 other abnormal CSM from the following list: • PtGDA ≥ 2cm in a 10 cm visual analog scale (VAS) • PhGDA ≥ 2cm 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) • HAQ-DI ≥0.5 Global muscle damage score 5 on a 10 cm VAS on the MDI. Participants should be on stable standard of care therapy if tolerated (a); if they are not able to tolerate it or have failed standard of care, medications should have washed out • (b): Participants on corticosteroid treatment (up to 20 mg prednisone or equivalent per • day) and/or up to 2, non-excluded, immunosuppressants on stable therapy for at least 4 weeks prior to Randomization or • Participants with previous failure of response or previous intolerance to corticosteroid and at least 1 additional immunosuppressant drug, and with steroid/immunosuppressants washed out. Participants should be willing to taper corticosteroid dose per protocol when stable or improving. For detailed inclusion criteria, refer to the protocol, Summary of changes (Pages 3-15)

Exclusion criteria 1

1. '3. Any condition that, in the opinion of the Investigator or Sponsor, would interfere with the evaluation of IP or interpretation of participant safety or study results. 4. Weight > 160 kg (352 pounds) at Screening. 5. History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or to a previous monoclonal antibody or human immunoglobulin therapy. 8. Major surgery within 8 weeks prior to Screening or elective surgery planned from Screening through end of the study. 10. History of clinically meaningful cardiac disease including unstable angina, myocardial infarction, congestive heart failure within 6 months prior to Randomization; 13. Participant who has given > 50 mL of blood or plasma within 30 days of Screening or > 499 mL of blood or plasma within 56 days of Screening (during a clinical study or at a blood bank donation) or plans to give blood or plasma during their participation in the study or up to 6 months after the last administration of IP, whichever is longer. 14. Transfusion with blood, packed red blood cells, platelets or treatment with plasmapheresis, or plasma exchange within 8 weeks prior to Randomization and for the total duration of the study participation. For detailed inclusion criteria, refer to the protocol, Summary of changes (Pages 3-15)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. TIS (Total improvement score) at Week 24.

Secondary endpoints 5

1. Proportion of participants with improvement of TIS ≥ 40 and without deterioration at 2 consecutive visits at 24 weeks. Proportion of participants with improvement of TIS ≥ 20 and without deterioration at 2 consecutive visits at 24 weeks
2. Change in the CDASI activity score from Baseline (Day 1) to Week 24
3. Proportion of participants on an OCS dose ≥ 10 mg of prednisone or equivalent at Baseline who achieve a clinically meaningful reduction in the OCS dose: either a 25% decrease or an OCS dose of 7.5 mg/day of prednisone or equivalent at Week 24
4. Serum concentration of daxdilimab (DAX) over time. Prevalence at Baseline and incidence and titer of antidrug antibodies directed against dax over time.
5. Incidence of TEAEs Incidence of TESAEs Incidence of TEAESIs: hypersensitivity reaction, including anaphylaxis, herpes zoster infection, severe (CTCAE Grade 3 or higher) viral infection/reactivation, opportunistic infection, and malignancy (except non-melanoma skin cancer).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Horizon Therapeutics Ireland Designated Activity Company

Sponsor organisation

Horizon Therapeutics Ireland Designated Activity Company

Address

70 Saint Stephen's Green

City

Dublin 2

Postcode

D02 E2X4

Country

Ireland

Scientific contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Nisha Jain

Public contact point

Organisation

Horizon Therapeutics Ireland Designated Activity Company

Contact name

Nisha Jain

Third parties 10

Locations

5 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Documents 100 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications