E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype |
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E.1.1.1 | Medical condition in easily understood language |
A cancer of the lymphatic system that affects the skin |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028483 |
E.1.2 | Term | Mycosis fungoides |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
The primary objective of the trial is to evaluate the efficacy of cobomarsen in subjects with MF. |
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E.2.2 | Secondary objectives of the trial |
• Investigate the safety and tolerability of cobomarsen in subjects with MF. • Characterize the population pharmacokinetics (PK) of cobomarsen in subjects with MF. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Must provide written informed consent (signed and dated) and any authorizations required by law and be able to comply with all study requirements. • Males or females, ≥ 18 years of age at the time of informed consent. • Biopsy-proven CTCL, MF subtype. • Clinical stage IB, II, or III, with staging based on Screening assessments. • Minimum mSWAT score of 10 at Screening. • Receipt of at least one prior therapy for CTCL (per the National Comprehensive Cancer Network [NCCN] guidelines for generalized skin involvement; e.g., topical, phototherapy, Total Skin Electron Beam Therapy [TSEBT] or systemic therapy). • Subjects of childbearing potential must agree to use highly effective methods of contraception as defined in the protocol. |
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E.4 | Principal exclusion criteria |
• Previous enrollment in a cobomarsen study. • Prior therapy with vorinostat or other HDAC inhibitors, or contraindication to an HDAC inhibitor. • Sézary syndrome or mycosis fungoides with B2 involvement. • Evidence of large cell transformation • Evidence of enlarged peripheral or central lymph node(s) > 1.5 cm in the long diameter or > 1.0 cm in the short diameter by radiographical imaging at Screening. • Any palpable peripheral node, regardless of size, that on physical examination is firm, irregular, clustered, or fixed, unless histologically confirmed to be non-malignant. • Evidence of visceral involvement related to MF at Screening. • Receipt of any the following treatments: - Macrolide or tetracycline antibiotics within 28 days prior to Screening; - More than 3 short courses of prednisone equivalent > 10 mg per day within 8 weeks prior to Screening; however, a stable regimen of systemic prednisone equivalent to ≤ 10 mg per day (or steroid equivalent) is permitted; - Total skin electron beam therapy within 4 weeks prior to Screening; - Investigational small molecule drug within 5 half-lives prior to Screening; - Investigational biologic drug within 5 half-lives prior to Screening; - Phototherapy within 4 weeks prior to Screening; - Antibody-directed or immunoglobulin-based immune therapy or other monoclonal antibody therapies within 8 weeks prior to Screening; - Previous chronic (more than 20 days total) high potency topical corticosteroid use within 4 weeks of Screening. Stable doses of low to medium potency topical corticosteroids are allowed; - Previous chronic (more than 20 days total) use of topical MF treatments (not listed in the bullets above) within 4 weeks prior to Screening; - Previous systemic MF treatments (not listed in the bullets above) within 4 weeks prior to Screening; - Previous treatment with an oligonucleotide. • Clinically significant liver disease within 1 year prior to Screening. • Positivity for human immunodeficiency virus (HIV), Hepatitis B surface antigen, or Hepatitis C at the time of Screening, • Clinically significant anemia, neutropenia or thrombocytopenia at Screening. • Previous or concurrent malignancy with the following exceptions: - Adequately treated basal cell or squamous cell carcinoma of the skin (adequate wound healing is required prior to study entry), - In situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to the study, - Or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry. • History of long QT syndrome and/or a history of persistent hypokalemia • Lactating or pregnant. • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure, as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment. • History of stroke or intracranial hemorrhage within 6 months prior to enrollment. • Clinically significant abnormalities which, in the opinion of the Investigator, would make subject unsuitable for inclusion in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Evaluation: Proportion of subjects achieving an objective response (complete response [CR] or partial response [PR]) of at least 4 months duration (ORR4) using composite global response criteria, including radiological imaging, flow cytometry, and the Modified Severity Weighted Assessment Tool (mSWAT) scoring. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Global response criteria collected 4 weeks after 4 months of sustained response (PR or CR) in the skin, and every 12 weeks thereafter.
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E.5.2 | Secondary end point(s) |
Efficacy measures • Key Secondary Endpoint: Progression-free survival (PFS). • Change from baseline and longitudinally during the study in Pruritus Numerical Rating Scale (NRS). • Change from baseline and longitudinally during the study in Skindex-29 total score. • Change from baseline and longitudinally during the study in Skindex-29 Subdomains (Symptoms, Emotion and Functionality). • Change from baseline and longitudinally during the study in Pain NRS. • Difference in drug tolerability by Patient Impression of Treatment Side Effects • Duration of composite global response for responding subjects. • Complete response rate (CRR). • Time to progression (TTP). • Time to maximal effect in mSWAT. • Proportion of subjects achieving ≥ 50% improvement in mSWAT of at least 4-months duration. • Proportion of subjects achieving ≥ 50% improvement in mSWAT of at least 28-days duration. • Percent of subjects achieving ≥ 50% improvement in mSWAT from baseline at 28 days and at 4 months. • Time to ≥ 50% improvement in mSWAT. • Duration of response in skin (no progression after achieving ≥ 50% improvement in mSWAT). • Change in pruritus medication utilization from baseline and incidence of pruritus medication utilization. • Overall survival. • Time to next treatment.
Safety and Tolerability Evaluations: • Incidence and severity of clinically significant adverse events (AEs) (including grade 3 and 4 AEs, treatment-related AEs, serious adverse events [SAEs], and AEs requiring discontinuation), physical examination findings, changes in electrocardiograms (ECGs), changes in laboratory parameters and changes in vital signs.
Pharmacokinetic Evaluation: • Population PK parameters. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Progression free survival, time to progression, overall survival, complete response rate: assessed throughout study Daily pruritus and pain score from Day 1 until follow up visit. Skindex-29, mSWAT: every 4 weeks to week 81, every 8 weeks thereafter Safety and tolerability: assessed throughout study PK: Days 1, 2, 3, 5, 8, 15, 29, every 4 weeks through week 81 and every 8 weeks thereafter. |
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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 | No |
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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | 40 |
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 |
Australia |
Austria |
Belgium |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 3 |
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 | 3 |
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 |