E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autoimmune Disorders Polymyositis and Dermatomyositis |
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E.1.1.1 | Medical condition in easily understood language |
inflammation of the muscles; inflammation of the skin |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10003816 |
E.1.2 | Term | Autoimmune disorders |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate efficacy of KZR-616 in patient with Polymyositis or Dermatomyositis |
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E.2.2 | Secondary objectives of the trial |
Secondary Objective(s) Evaluate safety and tolerability of KZR-616 in patients with PM or DM Evaluate pharmacokinetics (PK) of KZR-616 in patients with PM or DM.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 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.
9. Male patients with a partner of childbearing potential must be either congenitally sterile or surgically sterile (by vasectomy) or willing to use a condom in addition to having their female partner use another form of contraception (such as an intrauterine device, barrier method with spermicide, or hormonal contraceptive [eg, implant, injectable, patch, or oral]) from Screening until 12 weeks after the last dose of study drug, unless their partners are infertile or surgically sterile
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E.4 | Principal 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)
Nota Bene: Exclusion Criteria one to five are listed. Exclusion criteria six to twenty are listed in the protocol (28May2021) from page 8-11.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is: Mean change from start to end of KZR-616 treatment in the Total Improvement Score (TIS), which ranges from 0 to 100.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis period is from start to end of KZR-616 treatment for both sequence arms combined. A secondary analysis comparing KZR-616 to parallel placebo will be confined to the Baseline to Week 16 period.
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints are:
Proportion of patients with an increase ≥20 points on the TIS from start to end of KZR-616 treatment.
Proportion of patients from start to end of KZR-616 treatment meeting IMACS Definition of Improvement (DOI).
Absolute change and percent change from start to end of KZR-616 treatment in the IMACS individual CSAMs.
For patients with DM, the mean change from start to end of KZR-616 treatment in the CDASI
For patients with DM, the mean change from start to end of KZR-616 treatment in the Peak Pruritus NRS.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Start to end of KZR-616 treatment. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Germany |
Poland |
Czechia |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |