A Phase 2 Study of KZR-616 to Evaluate Safety and Efficacy in Patients With Active Polymyositis or Dermatomyositis

NCT04033926 | Completed Phase 2 Results FDA Drug

• 1 other identifier: KZR-616-003
• Study Type: interventional
• Target: 25
• Locations: 3 countries
• Sites: 14

Brief Summary

This was a Phase 2 randomized, double-blind, placebo-controlled, crossover, multicenter study to evaluate the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of treatment with KZR-616 in patients with active polymyositis (PM) or dermatomyositis (DM). Patients were evaluated for eligibility during the Screening Period. Eligible patients were stratified by diagnosis of DM or PM and randomized 1:1 to Arm A or Arm B of the study. During the 32-week treatment period, patients received study drug subcutaneously (SC) once weekly with 2 treatment periods of 16 weeks each. This study was conducted on an outpatient basis.

Conditions

Polymyositis; Dermatomyositis

Keywords

Myositis; Idiopathic inflammatory myopathies; Polymyositis; Dermatomyositis; Musculoskeletal Diseases; Muscular Diseases

Outcome Measures

Primary Outcomes (1)

• Mean Change in the Total Improvement Score (TIS) From Start to End of Zetomipzomib (KZR-616) Treatment Period

  The primary efficacy endpoint was mean change from start to end of zetomipzomib (KZR-616) Treatment Periods in the Total Improvement Score (TIS), which ranges from 0 to 100 \[low of 0 to high of 100, where higher scores are better\]. Mean change in TIS was calculated by comparing the Baseline and post Baseline observations for patients in both KZR-616 treatment periods combined. Note: TIS scores for placebo treatment periods are presented in this outcome measure but were not included in the primary outcome measure analysis.

  16 weeks in each Treatment Period (32 weeks total)

Secondary Outcomes (11)

• Proportion of Patients With TIS Response

  16 weeks in each Treatment Period (32 weeks total)

• Number of Patients Meeting the International Myositis Assessment and Clinical Studies Group (IMACS) Definition of Improvement (DOI)

  16 weeks in each Treatment Period (32 weeks total)

• Mean Percent Change From Baseline From Start to End of Treatment in the IMACS Individual CSAMs

  16 weeks in each Treatment Period (32 weeks total)

• Mean Change in CDASI From Start to End of Zetomipzomib (KZR-616) Treatment

  16 weeks in each Treatment Period (32 weeks total)

• Mean Change in PP-NRS From Start to End of Zetomipzomib (KZR-616) Treatment

  16 weeks in each Treatment Period (32 weeks total)

Study Arms (2)

Arm A

OTHER

* Treatment Period 1: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks * Treatment Period 2: Placebo SC weekly for 16 weeks

Drug: KZR-616; Drug: Placebo

Arm B

OTHER

* Treatment Period 1: Placebo SC weekly for 16 weeks * Treatment Period 2: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks

Drug: KZR-616; Drug: Placebo

Interventions

KZR-616 DRUG

Subcutaneous 30 mg weekly for 2 weeks, then 45 mg weekly for 14 weeks

Also known as: zetomipzomib

Arm A; Arm B

Placebo DRUG

Subcutaneous injection for 16 weeks

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients at least 18 years of age
• Body Mass Index (BMI) of 18 to 40 kg/m\^2
• Diagnosis of probable or definite DM or PM by the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria
• Must have their data reviewed by an adjudication committee to confirm eligibility unless at least 1 of the following is present:
• Muscle biopsy with evidence of active myositis within the last 6 months prior to or at Screening
• Electromyography or magnetic resonance imaging with evidence of active myositis within the last 6 months prior to Screening
• A creatine kinase (CK) ≥4 × upper limit of normal (ULN).
• Must have demonstrable muscle weakness as measured by the Manual Muscle Testing-8 muscle Groups (MMT-8) with a score ≥80/150 but ≤136/150 units and any 2 of the following:
• Physician Global Assessment (MDGA) visual analog scale (VAS) ≥2 cm
• Patient Global Assessment of Disease Activity (PtGADA) VAS ≥2 cm
• At least one muscle enzyme laboratory measurement ≥1.3 × ULN
• Myositis Disease Activity Assessment Tool (MDAAT) Extramuscular Global Activity VAS ≥1 cm.
• Documented inadequate response OR have demonstrated documented toxicity or intolerance to prior standard of care therapies
• Has had age-appropriate cancer screening that is up to date and negative for evidence of malignancy as per local standard of care

You may not qualify if:

• Has significant muscle damage or has a muscle damage VAS score ≥5 cm on the MDI
• Any other form of myositis or myopathy other than PM or DM
• Any condition that precludes the ability to quantitate muscle strength
• Has severe interstitial lung disease or has a pulmonary damage VAS score ≥5 cm on the Myositis Damage Index (MDI)
• Presence of autoinflammatory disease
• Use of nonpermitted medications or treatments within the specified washout periods prior to screening
• Patient has had recent serious or ongoing infection, or risk for serious infection
• Any of the following laboratory values at Screening:
• Estimated glomerular filtration rate \<45 mL/min
• Hemoglobin \<10 g/dL
• White blood cell (WBC) count \<3.0 × 10\^9/L
• Absolute neutrophil count (ANC) \<1.5 × 10\^9/L (1500/mm\^3)
• Platelet count \<100 × 10\^9/L
• Serum AST or serum ALT \>2.5 × ULN (unless considered consistent with muscle origin)
• Serum alkaline phosphatase \>2.5 × ULN

Sponsors & Collaborators

• Kezar Life Sciences, Inc.: lead

Study Sites (14)

KZR Research Site

Beverly Hills, California, 90211, United States

Location

KZR Research Site

Orange, California, 92868, United States

Location

KZR Research Site

Miami, Florida, 33136, United States

Location

KZR Research Site

Atlanta, Georgia, 30322, United States

Location

KZR Research Site

Kansas City, Kansas, 66160, United States

Location

KZR Research Site

Baltimore, Maryland, 21224, United States

Location

KZR Research Site

Ann Arbor, Michigan, 48109, United States

Location

KZR Research Site

Great Neck, New York, 11021, United States

Location

KZR Research Site

Duncansville, Pennsylvania, 16635, United States

Location

KZR Research Site

Pittsburgh, Pennsylvania, 15213, United States

Location

KZR Research Site

Austin, Texas, 78756, United States

Location

KZR Research Site

Henrico, Virginia, 23233, United States

Location

KZR Research Site

Prague, Czechia

Location

KZR Research Site

Göttingen, Germany

Location

MeSH Terms

Conditions

Polymyositis; Dermatomyositis; Myositis; Musculoskeletal Diseases; Muscular Diseases

Interventions

KZR-616

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Limitations and Caveats

* This study was not powered to detect statistical differences between treatment arms. * Crossover study design with no washout period may have confounded assessments. * Limited information from the safety follow-up as most patients elected to join the OLE study (NCT04628936).

Results Point of Contact

• Title: Regulatory Affairs
• Organization: Kezar Life Sciences, Inc

clinicaltrials@kezarbio.com

650-822-5600

Study Officials

• Kezar

  Kezar Life Sciences, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2019
• First Posted: July 26, 2019
• Study Start: January 14, 2020
• Primary Completion: April 6, 2022
• Study Completion: April 6, 2022
• Last Updated: November 19, 2025
• Results First Posted: January 3, 2024

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); US (12); CZ (1)