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

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

This was an open-label study to evaluate the long-term efficacy and safety of KZR-616 in patients with active polymyositis (PM) or dermatomyositis (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.

Study Overview

• Status: Completed
• Conditions: Dermatomyositis; Polymyositis
• Intervention / Treatment: Drug: KZR-616

Detailed Description

This was 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 (NCT04033926), up to and including the Week 32 Visit, prior to the first dose of open-label KZR-616.

Patients were 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 received 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 ended for all patients in Study KZR-616-003E when the last patient enrolled completed 48 weeks of dosing. Patients had 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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia
    • KZR Research Site
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • KZR Research Site
    • Orange, California, United States, 92868
      • KZR Research Site
  • Florida
    • Miami, Florida, United States, 33136
      • KZR Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • KZR Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • KZR Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • KZR Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • KZR Research Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • KZR Research Site
  • Texas
    • Austin, Texas, United States, 78756
      • KZR Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KZR-616 45 mg + standard therapy (open-label); All patients received 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 ended for all patients in Study KZR-616-003E when the last patient enrolled completed 48 weeks of dosing.	Drug: KZR-616; Subcutaneous 30 mg for 1 week, then 45 mg weekly; Other Names: KZR-616 Lyophile; zetomipzomib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Total Improvement Score (TIS) at OLE Week 48	The mean Total Improvement Score (TIS) at OLE Week 48, which ranges from 0 to 100 [low of 0 to high of 100, where higher scores are better]. The timeframe of 48 weeks was selected because it represented the maximum timeframe of dosing for the last patient enrolled as the study drug administration ended when the last patient enrolled completed 48 weeks of dosing.	48 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Pruritus Numeric Rating Scale Pruritis Numerical Rating Scale [NRS]	For DM patients, the Peak Pruritus Numeric Rating Scale ranges from a score of 0 to 10, with 0 representing no itch and 10 representing the worst itch imaginable during the worst moment within a 24-hour recall period.	60 weeks
Incidence, nature, and severity of treatment-emergent adverse events (TEAEs) with the causal relationship assessed by the investigator graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).	Safety	60 weeks

Collaborators and Investigators

• Sponsor: Kezar Life Sciences, Inc.
• Investigators: Study Director: Kezar Study Director, Kezar Life Sciences, Inc.

Publications and helpful links

Helpful Links

• Kezar Life Sciences, Inc. corporate website

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Actual): March 10, 2023
• Study Completion (Actual): June 12, 2023

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: November 9, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): June 5, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Myositis; Dermatomyositis; Musculoskeletal Diseases; Muscular Diseases; Polymyositis; Idiopathic inflammatory myopathies
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neuromuscular Diseases; Myositis; Dermatomyositis; Polymyositis
• Other Study ID Numbers: KZR-616-003E

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No