A study to evaluate the saftey and efficacy of KZR-616 for the tretament of patients with active inflammations of the muscle and the skin (rheumatic disease)

Phase 1

• Conditions: Autoimmune Disorders Polymyositis and Dermatomyositis; MedDRA version: 20.0Level: HLGTClassification code 10003816Term: Autoimmune disordersSystem Organ Class: 10021428 - Immune system disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2019-002605-22-CZ
• Lead Sponsor: Kezar Life Sciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-11-29
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Adult patients at least 18 years of age at the time of signing informed consent at Screening
2. Body Mass Index (BMI) of 18 to 40 kg/m x m
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:
a. Muscle biopsy with evidence of active myositis within the last 6 months prior to or at Screening
b. Electromyography or magnetic resonance imaging (MRI) with evidence of active myositis within the last 6 months prior to Screening
c. A CK =4 × upper limit of normal (ULN).
5. Must have demonstrable muscle weakness as measured by the MMT-8 with a score =80/150 but =136/150 units and any 2 of the following:
a. MDGA visual analog scale (VAS) =2 cm
b. PtGADA VAS =2 cm
c. At least one muscle enzyme laboratory measurement (ie, CK, aldolase, LDH) =1.3 × ULN
d. MDAAT Extramuscular Global Activity VAS =1 cm.
6. Documented inadequate response to a 12-week trial of corticosteroids or at least 1 immunosuppressant
(eg, methotrexate [MTX], mycophenolate mofetil [MMF], mycophenolate sodium [MPS], azathioprine
[AZA], leflunomide [LEF], tacrolimus, cyclosporine [CyA]) OR have demonstrated significant
documented toxicity or intolerance to such 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
8. Female patients of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and must agree to employ adequate birth control measures for the duration of the study.
Women of childbearing potential (WOCBP) must use highly effective and medically acceptable methods of contraception to prevent pregnancy during Screening and must agree to continue to practice
adequate contraception during the study and for 4 weeks after administration of the last dose of the studydrug.
For the purposes of this study, WOCBP are defined as: all postpubescent female patients, unless the
patient is postmenopausal (defined by amenorrhea for at least 2 years or amenorrhea for at least 1 year with confirmatory follicle stimulating hormone [FSH] level in the postmenopausal range as documented historically or measured by the central laboratory at Screening and if patient is not on supplementary
hormonal therapy) or if the patient is surgically sterile (ie, tubal ligation, hysterectomy, bilateral salpingoophorectomy).
Highly effective contraception is defined as the use of 2 barrier methods (eg, female diaphragm and
male condom), 1 barrier method with spermicide, intrauterine
device, or hormonal contraceptives
(eg, implant or oral). If using a hormonal form of contraception, it must have been stable for at least 4 weeks prior to Screening, and if using concomitant mycophenolate, the patient must use another
nonhormonal form of highly effective contraception. Abstinence will be acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation) and
withdrawal are not acceptable methods of contraception
9. Male patients must be either congenitally sterile or surgically sterile (vasectomy with documented confirmation of aspermia) or willing to use a condom in addition to having their female partner use another form of contraception (such a

Exclusion Criteria

1. Has significant muscle damage (eg, severe muscle atrophy, end-stage disease, postmyopathic DM) per Investigator opinion 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 (eg, metabolic or drug-induced myopathy, drug-induced myositis, juvenile PM or DM, inclusion body myositis, cancer-associated myositis [myositis diagnosed within 3 years, either before or after, of a diagnosis of any malignancy except for squamous or basal cell carcinoma of the skin or cervical carcinoma in situ], myositis in
overlap with another connective disease [eg, systemic lupus erythematosus{SLE}, systemic sclerosis,
rheumatoid arthritis {RA}], or muscular dystrophy); patients with secondary Sjogren’s syndrome, necrotizing myopathy, or antisynthetase syndrome are permitted to participate in this study
3. Any condition (eg, severe arthritis with limited range of motion or severe calcinosis) that, in the Investigator’s opinion, precludes the ability to quantitate muscle strength
4. Has severe interstitial lung disease per Investigator opinion or has a pulmonary damage VAS score =5 cm on the MDI
5. Presence of autoinflammatory disease (eg, psoriatic arthritis, axial spondyloarthropathy, inflammatory bowel disease)
6. Has received treatment with any of the following:
a. Oral prednisone (or prednisone equivalent) >20 mg/day at Screening or during the Screening Period, or initiation of oral prednisone during the Screening Period. If oral prednisone is being
used at Screening, use should be stable during the 2 weeks prior to Baseline
b. Use of nonsteroidal immunosuppressants other than oral MMF or MPS (=3 g/day or 2160 mg/day, respectively); oral, intramuscular (IM), or SC MTX (=25 mg/week); AZA (=2.5 mg/kg/day); LEF (=20 mg/day); tacrolimus (=3 g/day); or concurrent use of more than 1
nonsteroidal immunosuppressant at Baseline. If a permitted nonsteroidal immunosuppressant is being used, it must have used for at least 12 weeks and must have been taken at a stable dose (including stable route of administration) for the last 4 weeks prior to Screening. If MMF, MPS, MTX, AZA, LEF, or tacrolimus is being discontinued, it must be discontinued at least 4 weeks prior to Baseline
c. Antimalarials exceeding the recommended doses (hydroxychloroquine up to 400 mg/day or
6.5 mg/kg/day, whichever is less; chloroquine up to 250 mg/day, or quinacrine up to
100 mg/day are permitted) or taken at an unstable dose during the 12 weeks prior to Screening. If an antimalarial is being discontinued, it must be discontinued at least 4 weeks prior to
Baseline. Antimalarials are considered distinct from corticosteroids in (a) and nonsteroidal immunosuppressants in (b) above
d. Initiation of or use of an unstable dose of topical therapy (eg, corticosteroids, pimecrolimus) in the 4 weeks prior to Screening. If topical therapy is being discontinued, it must be discontinued
at least 4 weeks prior to Baseline.
7. Receipt of any of the following treatments within the following timeframes before Screening:
a. Oral corticosteroids at doses =1 mg/kg/day prednisone or equivalent: 4 weeks
b. Intravenous or IM corticosteroids: 4 weeks
c. Intra-articular therapies, such as corticosteroids or hyaluronic acid preparations: 4 weeks
d. Intravenous, SC, or IM Ig: 4 weeks
e. Cyclophosphamide or chlorambucil: 24 weeks
f. Prohibited nonbiologic nonsteroidal immunosuppressants or targeted therapies including, but
not limited to, CyA, dapsone, tofaci

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified