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

• ClinicalTrials.gov Identifier: NCT04033926
• Recruitment Status: Active, not recruiting
• First Posted: July 26, 2019
• Last Update Posted: March 14, 2022
• Sponsor: Kezar Life Sciences, Inc.
• Information provided by (Responsible Party): Kezar Life Sciences, Inc.

Study Description

Brief Summary:

"This is 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 will be evaluated for eligibility during the Screening Period. Eligible patients will be randomized 1:1 to Arm A or Arm B of the study.

During the 32-week treatment period, patients will receive study drug subcutaneously (SC) once weekly with 2 treatment periods of 16 weeks each.

This study will be conducted on an outpatient basis.

Condition or disease	Intervention/treatment	Phase
Polymyositis; Dermatomyositis	Drug: KZR-616; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 14, 2020
• Estimated Primary Completion Date: April 30, 2022
• Estimated Study Completion Date: July 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Arm A; 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; Subcutaneous 30 mg weekly for 2 weeks, then 45 mg weekly for 14 weeks; Drug: Placebo; Subcutaneous injection for 16 weeks
Arm B; 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; Subcutaneous 30 mg weekly for 2 weeks, then 45 mg weekly for 14 weeks; Drug: Placebo; Subcutaneous injection for 16 weeks

Outcome Measures

Primary Outcome Measures :

1. Primary Outcome Measure [ Time Frame: From start to end of KZR-616 treatment for both sequence arms combined. ]
   Mean change from start to end of KZR-616 treatment in the Total Improvement Score (TIS), which ranges from 0 to 100.

Secondary Outcome Measures :

1. Proportion of patients with an increase ≥20 points on the TIS from start to end of KZR-616 treatment. [ Time Frame: 16 weeks ]
2. Proportion of patients from start to end of KZR-616 treatment meeting International Myositis Assessment and Clinical Studies Group (IMACS) Definition of Improvement (DOI). [ Time Frame: 16 weeks ]
3. Absolute change from start to end of KZR-616 treatment in the IMACS individual core set activity measures (CSAMs) [ Time Frame: 16 weeks ]
4. Percent change from start to end of KZR-616 treatment in the IMACS individual CSAMs [ Time Frame: 16 weeks ]
5. For patients with DM, the mean change from start to end of KZR-616 treatment in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) [ Time Frame: 16 weeks ]
6. For patients with DM, the mean change from start to end of KZR-616 treatment in the Peak Pruritus Numeric Rating Scale. [ Time Frame: 16 weeks ]
   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.
7. Safety and tolerability of KZR-616 in patients with PM or DM as assessed by monitoring incidence and severity of adverse events (AEs) [ Time Frame: 40 weeks ]
8. Peak plasma concentration (Cmax) following KZR-616 injection [ Time Frame: Day 1 ]
9. Time to peak plasma concentration (Tmax) following KZR-616 injection [ Time Frame: Day 1 ]
10. Area under the plasma concentration versus time curve (AUC) following KZR-616 injection [ Time Frame: Day 1 ]
11. Half life (T1/2) following KZR-616 injection [ Time Frame: Day 1 ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Adult patients at least 18 years of age
2. Body Mass Index (BMI) of 18 to 40 kg/m2
3. Diagnosis of probable or definite DM or PM

4. Must 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 × 109/L
   4. Absolute neutrophil count (ANC) <1.5 × 109/L (1500/mm3)
   5. Platelet count <100 × 109/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

Contacts and Locations

Locations

United States, California

KZR Research Site

Beverly Hills, California, United States, 90211

KZR Research Site

Orange, California, United States, 92868

United States, Florida

KZR Research Site

Miami, Florida, United States, 33136

United States, Georgia

KZR Research Site

Atlanta, Georgia, United States, 30322

United States, Kansas

KZR Research Site

Kansas City, Kansas, United States, 66160

United States, Maryland

KZR Research Site

Baltimore, Maryland, United States, 21224

United States, Michigan

KZR Research Site

Ann Arbor, Michigan, United States, 48109

United States, New York

KZR Research Site

Great Neck, New York, United States, 11021

United States, Pennsylvania

KZR Research Site

Duncansville, Pennsylvania, United States, 16635

KZR Research Site

Pittsburgh, Pennsylvania, United States, 15213

United States, Texas

KZR Research Site

Austin, Texas, United States, 78756

United States, Virginia

KZR Research Site

Henrico, Virginia, United States, 23233

Czechia

KZR Research Site

Prague, Czechia

Germany

KZR Research Site

Göttingen, Germany

Poland

KZR Research Site

Bydgoszcz, Poland

KZR Research Site

Elbląg, Poland

KZR Research Site

Kraków, Poland

KZR Research Site

Szczecin, Poland

KZR Research Site

Wrocław, Poland

Sponsors and Collaborators

Kezar Life Sciences, Inc.

Investigators

• Study Director: Kezar; Kezar Life Sciences, Inc.

More Information

• Responsible Party: Kezar Life Sciences, Inc.
• ClinicalTrials.gov Identifier: NCT04033926
• Other Study ID Numbers: KZR-616-003
• First Posted: July 26, 2019
• Last Update Posted: March 14, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kezar Life Sciences, Inc.:

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

Additional relevant MeSH terms:

Dermatomyositis; Polymyositis; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin Diseases