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 |
Efficacy: To evaluate the long-term efficacy of KZR-616 in patients with PM or DM. Safety: To evaluate the long-term safety and tolerability of KZR-616 in patients with PM or DM.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must have successfully completed Study KZR-616-003 through Week 32, including the Week 32 Visit assessments, be willing and able to provide written informed consent prior to any study-related procedures, and be willing and able to comply with study requirements.
2. Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test prior to the first dose of KZR-616 in Study KZR-616-003E, and must agree to continue to use a highly effective method of birth control until completion of the study (or 30 days following the last dose of KZR-616 in case of early withdrawal). Women of childbearing potential are defined as 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 or local laboratory and if patient is not on supplementary hormonal therapy) or surgically sterile (ie, tubal ligation, hysterectomy, bilateral salpingoophorectomy).
3. Male patients must continue to use an effective contraception method (eg, condom with spermicide) for 1 week following their last dose of KZR-616 or be congenitally or surgically sterile (eg, vasectomy with documented confirmation of post-surgical aspermia).
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E.4 | Principal exclusion criteria |
1. Have clinical evidence of significant unstable or uncontrolled diseases other than the disease under study (eg, cardiac [including congestive heart failure, hypertension, angina, or myocardial infarction], pulmonary [including pulmonary hypertension or interstitial lung disease], hematologic, gastrointestinal, endocrinologic, hepatic, renal, neurological, or infectious disease, any ongoing SAE(s), or AE(s) ≥ Grade 3 by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]) that, in the opinion of the Investigator or Sponsor/designee, could confound the results of the study, put the patient at undue risk, or interfere with protocol adherence.
2. Has participated in any clinical study other than KZR-616-003 between the Week 32 Visit of Study KZR-616-003 and the first study visit of KZR-616-003E, if they are not on the same calendar day.
3. Are females who are breastfeeding or who plan to become pregnant during the study, or who are actively trying to conceive at the time of signing of the informed consent form (ICF).
4. Have hypersensitivity to KZR-616 or any of its excipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoints: • Mean change in TIS over time for all patients, for patients with DM only, for patients with PM only, and for patients with a myositis-associated antibody or myositis-specific antibody at the Screening Visit of Study KZR-616-003 • Proportion of patients meeting International Myositis Assessment and Clinical Studies Group (IMACS) definition of improvement (DOI) over time for patients with baseline core set measures as ascertained at the beginning of KZR-616-003 • Mean change and mean percentage change over time in the IMACS individual core set activity measures (CSAMs) and core set damage measures (CSDMs), stratified by all patients and patients with myositis-associated or myositis-specific antibody at the Screening Visit of Study KZR-616-003 • Mean change over time in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) for all patients with DM, and for patients with DM who have active skin manifestations at baseline of Study KZR-616-003E • Mean change over time in the Myositis Damage Index (MDI) • Mean change over time in muscle enzymes • Change in proportion and dose of corticosteroid and non-corticosteroid immunosuppressants during Study KZR-616-003E for all patients, and for patients taking corticosteroids or non-corticosteroid immunosuppressants at baseline of Study KZR-616-003E • Percentage of patients requiring additional medication for myositis treatment during Study KZR-616-003E • Mean change over time in the EuroQol 5-dimension 5-level (EQ-5D-5L) • Additional exploratory endpoints (Physician Global Impression of Change [MDGIC], Functional Index-2 [FI-2], Patient Global Impression of Change [PGIC], and Peak Pruritis Numerical Rating Scale [NRS]) will be assessed at multiple time points
Safety Endpoints: • Incidence, nature, and severity of adverse events (AEs) and serious adverse events (SAEs) • Incidence of AEs leading to KZR-616 discontinuation • Changes in standard laboratory parameters and vital signs
Exploratory Endpoint: • Relationships between clinical efficacy, clinical safety, and various biomarker endpoints including changes in circulating cytokine and whole blood gene expression
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints are given in E.5.1
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
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 |
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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 | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |