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 |
|
E.1.1.1 | Medical condition in easily understood language |
A cancer of the lymphatic system that affects the skin |
|
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 | 22.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028483 |
E.1.2 | Term | Mycosis fungoides |
E.1.2 | System Organ Class | 100000004864 |
|
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 who have shown disease progression following treatment with vorinostat in the SOLAR study. |
|
E.2.2 | Secondary objectives of the trial |
• Investigate the safety and tolerability of cobomarsen in subjects with MF. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must provide written informed consent (signed and dated), and any authorizations required by law and be able to comply with all study requirements. 2. Must have participated in the comparator arm of the SOLAR clinical trial and completed the study (confirmed disease progression). Subjects who discontinued from SOLAR for any reason other than confirmed disease progression on the comparator arm are not eligible. 3. Meets the following criteria per the central laboratory at Screening: a. Calculated creatinine clearance ≥ 40 mL/min using 24-hour creatinine clearance OR modified Cockcroft-Gault equation (using ideal body mass [IBM] instead of mass). b. AST and ALT ≤ 2.5 × the ULN; bilirubin ≤ 1.5 × ULN (except subjects with Gilbert's Syndrome who may have bilirubin ≤ 3.0 × ULN following discussion with the Sponsor). 4. Females who had a menstrual cycle within 2 years of Screening must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on their first dosing day. 5. Subjects of childbearing potential must agree to use highly effective methods of contraception. |
|
E.4 | Principal exclusion criteria |
Individuals who meet any of the following exclusion criteria are not to be enrolled in this study. 1. Sézary syndrome or mycosis fungoides with B2 involvement, defined as a documented history of B2 and/or B2 staging at the Screening visit. B2 means T-cell clone in peripheral blood + one of the following at Screening: a. ≥ 1000/μL Sézary cells by direct examination OR b. ≥ 1000/μL CD4+ CD26- OR c. ≥ 1000/μL CD4+ CD7- 2. Evidence of large cell transformation. 3. Evidence of visceral involvement related to MF at Screening. 4. Unresolved toxicities from prior vorinostat treatment, defined as having not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), grade 0 or 1. 5. 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; • Any CTCL systemic therapy after completion of the SOLAR study and prior to Day 1 for PRISM. 6. Positive test for blood (including trace) on urinalysis. Subjects with non-clinically significant etiology such as menstrual blood are allowed. 7. An active or uncontrolled infection defined as subjects who require systemic antibacterial, antiviral, or antifungal therapy within the last 7 days prior to Screening. 8. Clinically significant anemia (hemoglobin < 8 g/dL), neutropenia (absolute neutrophil count [ANC] < 1000/mm3) or thrombocytopenia (platelets < 50,000/mm3) at Screening. 9. Presence on ECG of QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 msec for males or > 470 msec for females or > 480 msec for subjects with bundle branch block, based on a mean of the triplicate ECG measurements collected at Screening. 10. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or inability to communicate or cooperate fully with the Investigator. 11. Lactating or pregnant. 12. Major surgery within 4 weeks of the first dose of study treatment. 13. Any active, clinically significant, unresolved adverse event (related or unrelated to study drug) from the prior study at the time of Screening. 14. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations). 15. Clinically significant abnormalities in medical history, physical examination, or laboratory values that, in the opinion of the Investigator, would make the subject unsuitable for inclusion in the study. |
|
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 mSWAT scoring. |
|
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.
|
|
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: • Pharmacokinetic Cmax and trough concentration analysis. |
|
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. |
|
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 |
|
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
|
|
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 |