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

• Sponsor: Kezar Life Sciences, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04033926
• Collaborator: (none)
• Enrollment: 24
• Locations: 19
• Arms: 2
• Anticipated Duration (Months): 30.5
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

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
• Anticipated 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: Jan 14, 2020
• Anticipated Primary Completion Date: Apr 30, 2022
• Anticipated Study Completion Date: Jul 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: 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
Other: 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 [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. [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). [16 weeks]

3. Absolute change from start to end of KZR-616 treatment in the IMACS individual core set activity measures (CSAMs) [16 weeks]

4. Percent change from start to end of KZR-616 treatment in the IMACS individual CSAMs [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) [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. [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) [40 weeks]

8. Peak plasma concentration (Cmax) following KZR-616 injection [Day 1]

9. Time to peak plasma concentration (Tmax) following KZR-616 injection [Day 1]

10. Area under the plasma concentration versus time curve (AUC) following KZR-616 injection [Day 1]

11. Half life (T1/2) following KZR-616 injection [Day 1]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

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

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

7. A creatine kinase (CK) ≥4 × upper limit of normal (ULN).

8. 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:

9. Physician Global Assessment (MDGA) visual analog scale (VAS) ≥2 cm

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

11. At least one muscle enzyme laboratory measurement ≥1.3 × ULN

12. Myositis Disease Activity Assessment Tool (MDAAT) Extramuscular Global Activity VAS ≥1 cm.

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

14. 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:

9. Estimated glomerular filtration rate <45 mL/min

10. Hemoglobin <10 g/dL

11. White blood cell (WBC) count <3.0 × 109/L

12. Absolute neutrophil count (ANC) <1.5 × 109/L (1500/mm3)

13. Platelet count <100 × 109/L

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

15. Serum alkaline phosphatase >2.5 × ULN

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

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

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

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

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

21. Clinical evidence of significant unstable or uncontrolled diseases

22. 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

	Site	City	State	Country	Postal Code
1	KZR Research Site	Beverly Hills	California	United States	90211
2	KZR Research Site	Orange	California	United States	92868
3	KZR Research Site	Miami	Florida	United States	33136
4	KZR Research Site	Atlanta	Georgia	United States	30322
5	KZR Research Site	Kansas City	Kansas	United States	66160
6	KZR Research Site	Baltimore	Maryland	United States	21224
7	KZR Research Site	Ann Arbor	Michigan	United States	48109
8	KZR Research Site	Great Neck	New York	United States	11021
9	KZR Research Site	Duncansville	Pennsylvania	United States	16635
10	KZR Research Site	Pittsburgh	Pennsylvania	United States	15213
11	KZR Research Site	Austin	Texas	United States	78756
12	KZR Research Site	Henrico	Virginia	United States	23233
13	KZR Research Site	Prague		Czechia
14	KZR Research Site	Göttingen		Germany
15	KZR Research Site	Bydgoszcz		Poland
16	KZR Research Site	Elbląg		Poland
17	KZR Research Site	Kraków		Poland
18	KZR Research Site	Szczecin		Poland
19	KZR Research Site	Wrocław		Poland

Sponsors and Collaborators

• Kezar Life Sciences, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kezar Life Sciences, Inc.
• ClinicalTrials.gov Identifier: NCT04033926
• Other Study ID Numbers: KZR-616-003
• First Posted: Jul 26, 2019
• Last Update Posted: Mar 14, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• 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

Study Results

No Results Posted as of Mar 14, 2022