PolymyositisPhase 2PRESIDIONCT04033926
A Phase 2 Study of KZR-616 to Evaluate Safety and Efficacy in Patients With Active Polymyositis or Dermatomyositis
A Phase 2 study testing KZR-616 in people with Polymyositis and Dermatomyositis, run by Kezar Life Sciences, Inc. at 14 sites in 3 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polymyositis, Dermatomyositis
- What is being tested?
- KZR-616
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 14 sitesin 3 countries
- Study dates
- 14 Jan 2020to 6 Apr 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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
- Total bilirubin >1.5 × ULN (3 × ULN for patients with documented Gilbert's syndrome)
- Thyroid stimulating hormone outside of the central laboratory normal range
- Immunoglobulin G (IgG) <500 mg/dL.
- Presence of New York Heart Association Class III or IV heart failure, or uncontrolled blood pressure, or prolonged QT interval
- Major surgery within 12 weeks before Screening or planned during the study period
- Clinical evidence of significant unstable or uncontrolled diseases
- 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
Trial locations and contacts
14 sites in 3 countries.
14 sites in 3 countries
United States12 sites
KZR Research Site
Ann Arbor, Michigan, 48109
KZR Research Site
Atlanta, Georgia, 30322
KZR Research Site
Austin, Texas, 78756
KZR Research Site
Baltimore, Maryland, 21224
KZR Research Site
Beverly Hills, California, 90211
KZR Research Site
Duncansville, Pennsylvania, 16635
KZR Research Site
Great Neck, New York, 11021
KZR Research Site
Henrico, Virginia, 23233
KZR Research Site
Kansas City, Kansas, 66160
KZR Research Site
Miami, Florida, 33136
KZR Research Site
Orange, California, 92868
KZR Research Site
Pittsburgh, Pennsylvania, 15213
About this study
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
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
- Being tested
- KZR-616, Placebo
- Keywords
- Myositis, Idiopathic inflammatory myopathies, Polymyositis, Dermatomyositis, Musculoskeletal Diseases, Muscular Diseases
- Medical subject headings
- Polymyositis, Dermatomyositis, Myositis, Musculoskeletal Diseases, Muscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KZR-616Drug
Also called zetomipzomib
Subcutaneous 30 mg weekly for 2 weeks, then 45 mg weekly for 14 weeks
PlaceboDrug
Subcutaneous injection for 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: KZR-616; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 16 weeks in each Treatment Period (32 weeks total)
Secondary outcomes (11)
Proportion of Patients With TIS Response
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.
Measured: 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)
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).
Measured: 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
Mean percent change from baseline of the IMACS CSAMs consisting of:
- Physician Global Assessment: physician assessment of patient's overall disease activity at present, high numbers indicate more severe disease activity [0-10]
- Patient Global Assessments of Disease Activity: patient assessment of their overall disease activity at present, high numbers indicate more severe disease activity [0-100]
- Manual Muscle Testing-8 Muscle Groups: scores range from 0 - 150, high scores are better
- Health Assessment Questionnaire-Disability Index: scores range from 0 - 3, high scores are worse
- Extramuscular Global Assessment of the Myositis Disease Activity Assessment Tool (2005 version): scores range from 0 - 10, high scores are worse
- Muscle enzymes (clinical laboratory assessments [CLA]): Summarize the most abnormal CLA (creatine kinase [CK], aldolase, lactate dehydrogenase [LDH], alanine aminotransferase [ALT], or aspartate aminotransferase [AST]) at baseline, lower scores are better
Measured: 16 weeks in each Treatment Period (32 weeks total)
Mean Change in CDASI From Start to End of Zetomipzomib (KZR-616) Treatment
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.
Measured: 16 weeks in each Treatment Period (32 weeks total)
Mean Change in PP-NRS From Start to End of Zetomipzomib (KZR-616) Treatment
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.
Measured: 16 weeks in each Treatment Period (32 weeks total)
PK of Zetomipzomib [KZR-616] (Cmax)
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.
Measured: Up to 5 hours
PK of Zetomipzomib [KZR-616] (Tmax)
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.
Measured: Up to 5 hours
PK of Zetomipzomib [KZR-616] (AUC)
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.
Measured: Up to 5 hours
PK of KZR-59587 (Cmax)
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.
Measured: Up to 5 hours
PK of KZR-59587 (Tmax)
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.
Measured: Up to 5 hours
PK of KZR-59587 (AUC)
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.
Measured: Up to 5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2019
- Study start14 Jan 2020
- Primary completion6 Apr 2022
- Study completion6 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PolymyositisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kezar Life Sciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kezar, Study director, Kezar Life Sciences, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04033926
- Sponsor's protocol ID
- KZR-616-003
- Acronym
- PRESIDIO
- Status last verified
- Nov 2025
- First submitted
- 23 Jul 2019
- Last updated
- 19 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04033926
- Acronym / sponsor ID
- PRESIDIO / KZR-616-003
- Conditions
- Polymyositis, Dermatomyositis
- Keywords
- Myositis, Idiopathic inflammatory myopathies, Polymyositis, Dermatomyositis, Musculoskeletal Diseases, Muscular Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Kezar Life Sciences, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Jan 2020 (actual)
- Primary completion
- 6 Apr 2022 (actual)
- Study completion
- 6 Apr 2022 (actual)
- First posted
- 26 Jul 2019 (actual)
- Results
- Posted 3 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Other | Drug: KZR-616, Drug: Placebo* 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 |
| Arm B | Other | Drug: KZR-616, Drug: Placebo* 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
- 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:
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KZR-616Also: zetomipzomibSubcutaneous 30 mg weekly for 2 weeks, then 45 mg weekly for 14 weeks | Drug | Arm A, Arm B |
| PlaceboSubcutaneous injection for 16 weeks | Drug | Arm A, Arm B |
Primary outcome
Mean Change in the Total Improvement Score (TIS) From Start to End of Zetomipzomib (KZR-616) Treatment Period
Time frame: 16 weeks in each Treatment Period (32 weeks total)
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.
11 secondary outcomes
Proportion of Patients With TIS Response
Time frame: 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)
Time frame: 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
Time frame: 16 weeks in each Treatment Period (32 weeks total)
Mean Change in CDASI From Start to End of Zetomipzomib (KZR-616) Treatment
Time frame: 16 weeks in each Treatment Period (32 weeks total)
Mean Change in PP-NRS From Start to End of Zetomipzomib (KZR-616) Treatment
Time frame: 16 weeks in each Treatment Period (32 weeks total)
PK of Zetomipzomib [KZR-616] (Cmax)
Time frame: Up to 5 hours
PK of Zetomipzomib [KZR-616] (Tmax)
Time frame: Up to 5 hours
PK of Zetomipzomib [KZR-616] (AUC)
Time frame: Up to 5 hours
PK of KZR-59587 (Cmax)
Time frame: Up to 5 hours
PK of KZR-59587 (Tmax)
Time frame: Up to 5 hours
PK of KZR-59587 (AUC)
Time frame: Up to 5 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Polymyositis
RecruitingPhase 2
FAST for DM - Fatty Acid Supplementation Trial (FAST) for Dermatomyositis (DM)
Dermatomyositis (DM), Juvenile Dermatomyositis (JDM)
Active, not recruitingPhase 2
A Study to Evaluate Safety and Efficacy of Empasiprubart in Adults With Dermatomyositis
Dermatomyositis, Myositis
RecruitingObservational study
Natural History of Inflammatory Muscle Diseases
Inflammation In Skeletal Muscle
RecruitingPhase 1
A Study to Investigate the Safety and Preliminary Efficacy of ALLO-329, an Allogeneic CAR T-cell Therapy, in Adults With Autoimmune Disease
Systemic Lupus Erythematosus (With and Without Nephritis), Idiopathic Inflammatory Myopathy
RecruitingPhase 2
Topical Ruxolitinib Cream for Refractory Cutaneous Dermatomyositis
Dermatomyositis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kezar study director
Kezar Life Sciences, Inc.
14 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KZR-616 in people with Polymyositis and Dermatomyositis, run by Kezar Life Sciences, Inc. at 14 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Czechia, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change in the Total Improvement Score (TIS) From Start to End of Zetomipzomib (KZR-616) Treatment Period (time frame: 16 weeks in each Treatment Period (32 weeks total)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2025.