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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05669014




Registration number
NCT05669014
Ethics application status
Date submitted
20/12/2022
Date registered
30/12/2022

Titles & IDs
Public title
A Phase 2 Proof of Concept Study to Evaluate the Efficacy and Safety of Daxdilimab in Participants With Dermatomyositis (DM) or Anti-synthetase Inflammatory Myositis (ASIM)
Scientific 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.
Secondary ID [1] 0 0
2022-502810-10-00
Secondary ID [2] 0 0
HZNP-DAX-205
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Inflammatory Myositis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Neurological 0 0 0 0
Other neurological disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Daxdilimab
Treatment: Drugs - Placebo

Experimental: Daxdilimab - Daxdilimab will be administered by subcutaneous (SC) injection over a total of 44 weeks.

Placebo comparator: Placebo - Matching placebo will be administered by SC injection over a total of 24 weeks, then will be administered active drug by SC injection up to Week 44


Treatment: Drugs: Daxdilimab
Participants will be administered daxdilimab by subcutaneous (SC) injection

Treatment: Drugs: Placebo
Participants will be administered identically matching placebo by SC injection over a total of 24 weeks, then participants will be given active treatment for the remainder of the study.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Efficacy of daxdilimab compared to placebo as measured by Total Improvement Score (TIS)
Timepoint [1] 0 0
At Week 24
Secondary outcome [1] 0 0
Proportion of participants with improvement of TIS = 40 and without deterioration at 2 consecutive visits at 24 weeks
Timepoint [1] 0 0
At 24 Weeks
Secondary outcome [2] 0 0
Proportion of participants with improvement of TIS = 20 and without deterioration at 2 consecutive visits at 24 weeks
Timepoint [2] 0 0
At 24 Weeks
Secondary outcome [3] 0 0
Change in the cutaneous dermatomyositis disease area and severity index (CDASI) activity score from Baseline (Day 1) to Week 24
Timepoint [3] 0 0
Baseline (Day1) to Week 24
Secondary outcome [4] 0 0
Proportion of participants on an oral corticosteroid (OCS) dose = 10 mg of prednisone or equivalent at baseline who achieve a clinically meaningful reduction in the OCS dose at Week 24
Timepoint [4] 0 0
Baseline to Week 24
Secondary outcome [5] 0 0
Serum concentration of daxdilimab over time
Timepoint [5] 0 0
Baseline to Week 56
Secondary outcome [6] 0 0
Proportion of the participants with anti-drug antibodies (ADA) positive post-baseline only or boosted their pre-existing ADA during the study period.
Timepoint [6] 0 0
Baseline to Week 56
Secondary outcome [7] 0 0
Incidence of ADA directed against daxdilimab over time
Timepoint [7] 0 0
Baseline to Week 56
Secondary outcome [8] 0 0
Titer of ADA to daxdilimab over time
Timepoint [8] 0 0
Baseline to Week 56
Secondary outcome [9] 0 0
Incidence of treatment emergent adverse events (TEAEs)
Timepoint [9] 0 0
Baseline to Week 56
Secondary outcome [10] 0 0
Incidence of treatment emergent serious adverse events (TESAEs)
Timepoint [10] 0 0
Baseline to Week 56
Secondary outcome [11] 0 0
Incidence of treatment emergent adverse events of special interest (TEAESIs)
Timepoint [11] 0 0
Baseline to Week 56

Eligibility
Key inclusion criteria
Key

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) = 2 cm 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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
6. Any underlying condition that in the opinion of the Investigator significantly predisposes the participant to infection (eg. hepatitis C).
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. All participants will undergo testing for hepatitis B virus serology as defined in the protocol.
9. Active tuberculosis (TB), or a positive interferon gamma (IFN-?) 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 10 cm 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
22/05/2027
Actual
Sample size
Target
96
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Campbelltown Hospital - Campbelltown
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
Brazil
State/province [2] 0 0
Minas Gerais
Country [3] 0 0
Brazil
State/province [3] 0 0
Rio Grande Do Sul
Country [4] 0 0
Czechia
State/province [4] 0 0
Praha, Hlavní Mesto
Country [5] 0 0
Mexico
State/province [5] 0 0
Mexico city
Country [6] 0 0
Mexico
State/province [6] 0 0
Monterrey
Country [7] 0 0
Spain
State/province [7] 0 0
a Coruña
Country [8] 0 0
Spain
State/province [8] 0 0
Sevilla
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Merseyside
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Midlothian

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://www.amgen.com/datasharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05669014