Open-label Extension to the Phase 2 Crossover Study (PRESIDIO) Evaluating KZR-616 in Patients With PM and DM.

Study Overview
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Brief Summary
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This is an open-label study to evaluate the long-term efficacy and safety of KZR-616 in patients with active PM or DM who completed the double-blind treatment period of Study KZR-616-003, up to and including the Week 32 Visit, prior to the first dose of open-label KZR-616.

Detailed Description
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This is an open-label study to evaluate the long-term efficacy and safety of KZR-616 in patients with active polymyositis or dermatomyositis who completed the double-blind treatment period of Study KZR-616-003, up to and including the Week 32 Visit, prior to the first dose of open-label KZR-616. Patients will be evaluated for eligibility according to the entry criteria at, or within 8 weeks after, the Week 32 Visit (ie, the End of Treatment [EOT] Visit [Visit 34]) of Study KZR-616-003. All patients will receive a subcutaneous (SC) injection of 30 mg KZR-616 at Visit 1 (Day 1), followed by weekly SC injections of 45 mg KZR-616 up to a maximum of 96 weeks. Study drug administration will end for all patients in Study KZR-616-003E when the last patient enrolled has completed 48 weeks of dose. Patients will have a final follow-up visit 12 weeks after their last dose of KZR-616 (End of Study [EOS] Visit), for a maximum potential length of participation of 108 weeks.

Official Title
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An Open-label Extension to the Phase 2 Randomized, Double-blind, Placebo-controlled, Crossover Multicenter Study to Evaluate the Safety and Efficacy of KZR-616 in the Treatment of Patients With Active Polymyositis or Dermatomyositis

Conditions
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Polymyositis, Dermatomyositis

Intervention / Treatment
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* Drug: KZR-616


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have successfully completed Study KZR-616-003 through Week 32, including the Week 32 Visit assessments Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test prior to the first dose of KZR-616 in KZR-616-003E, and must agree to continue to use a highly effective method of birth control until completion of the study. Male patients must continue to use an effective contraception method for 1 week following their last dose of KZR-616 or be congenitally or surgically sterile. Exclusion Criteria: Have clinical evidence of significant unstable or uncontrolled diseases other than the disease under study, that in the opinion of the Investigator or Sponsor/designee, could confound the results of the study, put the patient at undue risk, or interfere with protocol adherence. Has participated in any clinical study other than KZR-616-003 between the Week 32 Visit of Study KZR-616-003 and the first study visit of KZR-616-003E, if they are not on the same calendar day. Are females who are breastfeeding or who plan to become pregnant during the study, or who are actively trying to conceive at the time of signing of the informed consent form. Have hypersensitivity to KZR-616 or any of its excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All patients will receive a SC injection of 30 mg KZR-616 at Visit 1 (Day 1), followed by weekly SC injections of 45 mg KZR-616 up to a maximum of 96 weeks. Study drug administration will end for all patients when the last patient enrolled has completed 48 weeks of dosing.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KZR-616 45 mg + standard therapy (open-label)<br>All patients will receive a SC injection of 30 mg KZR-616 at Visit 1 (Day 1), followed by weekly SC injections of 45 mg KZR-616 up to a maximum of 96 weeks. Study drug administration will end for all patients in Study KZR-616-003E when the last patient enrolled has completed 48 weeks of dosing. | Drug: KZR-616<br>* KZR-616 subcutaneous injection<br>* Other names: KZR-616 Lyophile;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Improvement Score (TIS) | Mean change in TIS over time for all patients, for patients with DM only, for patients with PM only, and for patients with a myositis-associated antibody or myositis-specific antibody. | 80 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Improvement Score (TIS) response | Proportion of patients by TIS response (minimal response = TIS ≥ 20, moderate response = TIS ≥ 40, major response = TIS ≥ 60) | 80 weeks | 
| International Myositis Assessment and Clinical Studies Group (IMACS) Definition of Improvement (DOI) | Proportion of patients meeting IMACS definition of improvement (DOI) over time for patients with baseline core set measures. | 80 weeks | 
| International Myositis Assessment and Clinical Studies Group (IMACS) individual Core Set Activity Measures (CSAMs) | Mean change and mean percentage change over time in the IMACS individual CSAMs and CSDMs, stratified by all patients and patients with myositis-associated or myositis-specific antibody. | 80 weeks | 
| Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) | Mean change over time in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) for all patients with DM, and for patients with DM who have active skin manifestations at baseline of Study KZR-616-003E. | 60 weeks | 
| Corticosteroid and non-corticosteroid immunosuppressants | Change in proportion and dose of corticosteroid and non-corticosteroid immunosuppressants during Study KZR-616-003E for all patients, and for patients taking corticosteroids or non-corticosteroid immunosuppressants at baseline of Study KZR-616-003E. | 60 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myositis, Idiopathic inflammatory myopathies, Polymyositis, Dermatomyositis, Musculoskeletal Diseases, Muscular Diseases