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

Dermatomyositis Clinical Trial

— PRESIDIO  

Official title:

A 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04033926
• Other study ID #: KZR-616-003
• Status: Completed
• Phase: Phase 2
• Start date: January 14, 2020
• Est. completion date: April 6, 2022

Study information

• Verified date: December 2023
• Source: Kezar Life Sciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 6, 2022
• Est. primary completion date: April 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult patients at least 18 years of age

2. Body Mass Index (BMI) of 18 to 40 kg/m^2

3. Diagnosis of probable or definite DM or PM by the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria

4. Must have their data reviewed by an adjudication committee to confirm eligibility unless at least 1 of the following is present:

1. Muscle biopsy with evidence of active myositis within the last 6 months prior to or at Screening

2. Electromyography or magnetic resonance imaging with evidence of active myositis within the last 6 months prior to Screening

3. A creatine kinase (CK) =4 × upper limit of normal (ULN).

5. 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:

1. Physician Global Assessment (MDGA) visual analog scale (VAS) =2 cm

2. Patient Global Assessment of Disease Activity (PtGADA) VAS =2 cm

3. At least one muscle enzyme laboratory measurement =1.3 × ULN

4. Myositis Disease Activity Assessment Tool (MDAAT) Extramuscular Global Activity VAS =1 cm.

6. Documented inadequate response OR have demonstrated documented toxicity or intolerance to prior standard of care therapies

7. Has had age-appropriate cancer screening that is up to date and negative for evidence of malignancy as per local standard of care

Exclusion Criteria:

1. Has significant muscle damage or has a muscle damage VAS score =5 cm on the MDI

2. Any other form of myositis or myopathy other than PM or DM

3. Any condition that precludes the ability to quantitate muscle strength

4. Has severe interstitial lung disease or has a pulmonary damage VAS score =5 cm on the Myositis Damage Index (MDI)

5. Presence of autoinflammatory disease

6. Use of nonpermitted medications or treatments within the specified washout periods prior to screening

7. Patient has had recent serious or ongoing infection, or risk for serious infection

8. Any of the following laboratory values at Screening:

1. Estimated glomerular filtration rate <45 mL/min

2. Hemoglobin <10 g/dL

3. White blood cell (WBC) count <3.0 × 10^9/L

4. Absolute neutrophil count (ANC) <1.5 × 10^9/L (1500/mm^3)

5. Platelet count <100 × 10^9/L

6. Serum AST or serum ALT >2.5 × ULN (unless considered consistent with muscle origin)

7. Serum alkaline phosphatase >2.5 × ULN

8. Total bilirubin >1.5 × ULN (3 × ULN for patients with documented Gilbert's syndrome)

9. Thyroid stimulating hormone outside of the central laboratory normal range

10. Immunoglobulin G (IgG) <500 mg/dL.

9. Presence of New York Heart Association Class III or IV heart failure, or uncontrolled blood pressure, or prolonged QT interval

10. Major surgery within 12 weeks before Screening or planned during the study period

11. Clinical evidence of significant unstable or uncontrolled diseases

12. Any active or suspected malignancy, including myeloproliferative or lymphoproliferative disorder, or history of documented malignancy within the last 5 years before Screening or within 3 years of diagnosis of myositis, except appropriately excised and cured cervical carcinoma in situ or basal or squamous cell carcinoma of the skin

Related Conditions & MeSH terms

• Dermatomyositis
• Polymyositis

Intervention

Drug:
• KZR-616
Subcutaneous 30 mg weekly for 2 weeks, then 45 mg weekly for 14 weeks
• Placebo
Subcutaneous injection for 16 weeks

Locations

Country	Name	City	State
Czechia	KZR Research Site	Prague
Germany	KZR Research Site	Göttingen
United States	KZR Research Site	Ann Arbor	Michigan
United States	KZR Research Site	Atlanta	Georgia
United States	KZR Research Site	Austin	Texas
United States	KZR Research Site	Baltimore	Maryland
United States	KZR Research Site	Beverly Hills	California
United States	KZR Research Site	Duncansville	Pennsylvania
United States	KZR Research Site	Great Neck	New York
United States	KZR Research Site	Henrico	Virginia
United States	KZR Research Site	Kansas City	Kansas
United States	KZR Research Site	Miami	Florida
United States	KZR Research Site	Orange	California
United States	KZR Research Site	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Kezar Life Sciences, Inc.

Countries where clinical trial is conducted

United States,  Czechia,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)