KZR-616-003

Kezar Life Sciences, Inc.

4000 Shoreline Court, Suite 300, South San Francisco, United States, 94080

Regulatory Affairs, Kezar Life Sciences, Inc., 001 6508225600, PRESIDIO@kezarbio.com

Clinical Science, Kezar Life Sciences, Inc., 001 6508225600, PRESIDIO@kezarbio.com

No

No

No

Final

27 Jul 2023

Yes

06 Apr 2022

Yes

06 Apr 2022

No

Evaluate efficacy of KZR-616 in patient with Polymyositis (PM) or Dermatomyositis (DM)

Investigators and all parties involved in this study conducted the study in adherence to the ethical principles based on the Declaration of Helsinki, ICH guidelines for cGCP, and the applicable laws and regulatory requirements. IRB/IEC approval of the study and relevant study information (e.g. protocol, informed consent form (ICF), patient-facing materials) was obtained before initiation of study sites or releasing study drug to sites. Extensions/renewals of the approval were obtained as necessary. Written informed consent (signed and dated) was obtained before any study-related procedures were performed. Patients were given every opportunity to ask for clarification and were given ample time to consider the study. Patients may refuse to enter the study or to withdraw from the study at any time, without consequences for their further care or penalty or loss of benefits to which the patient is otherwise entitled. All Investigators promptly reported any new information that may have adversely affected patient safety or the study conduct and submitted study status summaries to the IRB/IEC as required. Patients were informed about new information available that was relevant to their willingness to continue participation in the study and were reconsented to the IRB/IEC/regulatory authorities currently approved ICF. Patients’ identity remained confidential in any presentations or publications of the study results. All personal data collected and processed for the purposes of this study were managed with adequate precautions to ensure confidentiality of data, and in accordance with the applicable laws and regulations on personal data protection. A study-specific Data Monitoring Committee (Safety Review Committee per BfArM) met to review accumulating safety data, study conduct and progress and to make recommendations about the study progress on a regular basis. Each voting member provided their recommendation at the conclusion of each meeting.

14 Jan 2020

No

No

Czechia: 1

United States: 24

25

1

0

0

0

0

0

0

21

4

0

Treatment Period 1

Randomised - controlled

No

zetomipzomib

KZR-616

Powder for solution for injection

Subcutaneous use

30 mg subcutaneous injections of zetomipzomib once weekly for the first two weeks, then 45 mg zetomipzomib SC QW for the remaining 14 weeks of treatment

sterile water for injection

Solvent for parenteral use

Subcutaneous use

Matching placebo was administered by SC injection QW to patients in Arm B during Period 1 and patients in Arm A during Period 2.

Treatment Period 2

Randomised - controlled

No

sterile water for injection

Solvent for parenteral use

Subcutaneous use

Matching placebo was administered by SC injection QW to patients in Arm B during Period 1 and patients in Arm A during Period 2.

zetomipzomib

KZR-616

Powder for solution for injection

Subcutaneous use

30 mg subcutaneous injections of zetomipzomib once weekly for the first two weeks, then 45 mg zetomipzomib SC QW for the remaining 14 weeks of treatment

Treatment Period 1

Arm A: Period 1 (Zetomipzomib)

Arm B: Period 1 (Placebo)

Arm A: Period 2 (Placebo)

Arm B: Period 2 (Zetomipzomib)

Arm A: Period 1 (Zetomipzomib)

Zetomipzomib 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks

Arm B: Period 1 (Placebo)

Placebo SC weekly for 16 weeks

Arm A: Period 2 (Placebo)

Placebo SC weekly for 16 weeks

Arm B: Period 2 (Zetomipzomib)

Zetomipzomib 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks

Zetomipzomib First, Then Placebo (Arm A)

Treatment Period 1: Zetomipzomib 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks Treatment Period 2: Placebo SC weekly for 16 weeks

Placebo First, Then Zetomipzomib (Arm B)

Treatment Period 1: Placebo SC weekly for 16 weeks Treatment Period 2: Zetomipzomib 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks

Arm A: Period 1 + Arm B: Period 2

All patients treated with zetomipzomib. Arm A - Treatment Period 1: Zetomipzomib 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks Arm B - Treatment Period 2: Zetomipzomib 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks

Baseline

For the statistical analysis of the primary endpoint, Total Improvement Score (TIS) was assessed using Week 0 as the baseline (before zetomipzomib [KZR-616] administration) timepoint for both Arm A and Arm B patients.

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.

Primary

16 weeks in each Treatment Period (32 weeks total)

Mean change in TIS was calculated by comparing the baseline and post baseline observations within patients for the zetomipzomib (KZR-616) treatment periods combined (Arm A: Period 1 + Arm B: Period 2). Due to system limitations, the number of "Subjects in this analysis" reads 44 but should be 22. This discrepancy occurs from subjects being counted twice, once at baseline group and once in the treatment group, even though they should only be counted once.

Arm A: Period 1 + Arm B: Period 2 v Baseline

44

Pre-specified

The proportion of patients with an increase of ≥ 20 points on the TIS from start to end of zetomipzomib (KZR-616) treatment. TIS response is categorized by the following improvement thresholds: Minimal response = TIS ≥ 20 Moderate response = TIS ≥ 40 Major response = TIS ≥ 60 This endpoint was assessed by comparing Week 16 versus Week 0 for patients allocated to Arm A and Week 32 versus Week 16 for patients allocated to Arm B. This re-baselining approach was utilized to maximize the precision for assessment of zetomipzomib effect in Arm B.

Secondary

32 weeks

The IMACS DOI is ≥ 20% improvement in at least 3 of 6 core set activity measures, with no more than 2 core set activity measures (CSAMs) worsening by ≥ 25% (Manual Muscle Testing-8 Muscle Groups [MMT-8] could not be a worsening measure).

Secondary

32 weeks

Mean percent change from baseline of the IMACS CSAMs which consists of: Physician Global Assessment (MDGA) - 5 point Likert scale and 10cm Visual Analogue Scale Patient Global Assessments of Disease Activity (PtGADA) - 10cm Visual Analogue Scale Manual Muscle Testing-8 Muscle Groups (MMT-8) - scores range from 0 - 260, high scores are better Health Assessment Questionnaire-Disability Index (HAQ-DI) - scores range from 0 - 3, high scores are worse Myositis Disease Activity Assessment Tool (MDAAT, 2005 version) - scores range from 0 - 60, high scores are worse Muscle enzymes (clinical laboratory assessments): Summarize the most abnormal clinical laboratory assessment at baseline between creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST).

Secondary

32 weeks

Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) is a clinician scored single-page instrument that separately measures activity and damage, which consists of three (3) activity measures and two (2) damage measures which are assessed over 15 body areas. Scores range from 0-100 for activity and from 0-32 for damage, with higher scores indicating more severe disease.

Secondary

32 weeks

The Peak Pruritus Numeric Rating Scale (PP-NRS) is used to evaluate severity of itch in DM patients. Scores range from 0-10, with zero (0) representing no itch and ten (10) representing the worst itch imaginable within a 24-hour recall period.

Secondary

32 weeks

This is the maximum observed plasma concentration (Cmax) observed after administration of the first dose of KZR-616 (either Week 0 or Week 16). The pharmacokinetic (PK) parameters were calculated using all timepoints at which the concentration was measured, ie. pre-dose and 30 minutes, and 4 hours post-dose, with an additional sample obtained at 0.25, 1, or 2 hours post-dose.

Secondary

4 hours

This is the time to maximum observed plasma concentration (tmax) observed after administration of the first dose of KZR-616 (either Week 0 or Week 16). The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 30 minutes, and 4 hours postdose, with an additional sample obtained at 0.25, 1, or 2 hours postdose.

Secondary

4 hours

This is the area under the curve (AUC) from predose through 4 hour postdose observed after administration of the first dose of KZR-616 (either Week 0 or Week 16). The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 30 minutes, and 4 hours postdose, with an additional sample obtained at 0.25, 1, or 2 hours postdose.

Secondary

4 hours

This is the maximum observed plasma concentration of KZR-59587 (Cmax) observed after administration of the first dose of KZR-616 (either Week 0 or Week 16). The pharmacokinetic (PK) parameters were calculated using all timepoints at which the concentration was measured, ie. pre-dose and 30 minutes, and 4 hours post-dose, with an additional sample obtained at 0.25, 1, or 2 hours post-dose.

Secondary

4 hours

This is the time to maximum observed plasma concentration of KZR-59587 (tmax) observed after administration of the first dose of KZR-616 (either Week 0 or Week 16). The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 30 minutes, and 4 hours postdose, with an additional sample obtained at 0.25, 1, or 2 hours postdose.

Secondary

4 hours

This is the area under the curve of KZR-59587 (AUC) from predose through 4 hour postdose observed after administration of the first dose of KZR-616 (either Week 0 or Week 16). The PK parameters were calculated using all timepoints at which the concentration was measured, ie. predose and 30 minutes, and 4 hours postdose, with an additional sample obtained at 0.25, 1, or 2 hours postdose.

Secondary

4 hours

Up to 40 weeks

25.1

Arm A: Period 1 (Zetomipzomib)

Arm A: Period 2 (Placebo)

Arm B: Period 1 (Placebo)

Arm B: Period 2 (Zetomipzomib)