Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype MedDRA version: 22.0 Level: LLT Classification code 10028483 Term: Mycosis fungoides System Organ Class: 100000004864
Conditions
Sponsors
miRagen Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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. Additional Criteria for Crossover Period: • Must have participated in the comparator arm of the randomized period and completed the randomized period (confirmed disease progression in skin). Subjects who discontinued from the randomized period of SOLAR for any reason other than confirmed skin disease progression on the comparator arm are not eligible. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 63 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 63
Exclusion criteria
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. • Current evidence of large cell transformation (LCT), defined as > 25% of the lymphocytes at least 4 × the size of normal lymphocytes. Current evidence refers to LCT diagnosis from biopsy performed within 4 months prior to randomization. Subjects with a history of LCT but with a negative current biopsy (within 4 months) are eligible, provided there is no clinical indication for chemotherapy. • 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. A subject with one or more enlarged lymph node(s) may be allowed, provided that a representative lymph node has been confirmed (via biopsy or positron emission tomography [PET] scan) to be N0-N2 or SUV = 5 within the 3 months prior to Day 1, and there has not been an appearance of new abnormal lymph nodes since the biopsy or PET scan. Subjects with uncharacterized enlarged lymph nodes (i.e. not confirmed by biopsy or PET scan) will not be allowed. • 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 (= 7 days) 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 or radiotherapy 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. - Patients on chronic prophylactic (for prevention, more than 20 days per month) nonsteroidal antipruritic medications within 4 weeks of screening are excluded. Patients on symptomatic (for current symptoms) stable nonsteroidal antipruritic medications (dose and frequency remain the same for at least 1 month prior to screening) for symptomatic pruritus are allowed. • 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 ce
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to evaluate the efficacy of cobomarsen in subjects with MF.;Secondary Objective: • Investigate the safety and tolerability of cobomarsen in subjects with MF. • Characterize the population pharmacokinetics (PK) of cobomarsen in subjects with MF. • During the crossover portion of the study: - Evaluate the efficacy, safety and tolerability of cobomarsen in subjects with MF who have shown disease progression following treatment with vorinostat.;Primary end point(s): Primary Efficacy Evaluation: Proportion of subjects achieving an objective skin response (complete response [CR] or partial response [PR]) of at least 4 months duration (ORR4) using the Modified Severity Weighted Assessment Tool (mSWAT) scoring.;Timepoint(s) of evaluation of this end point: Response criteria collected 4 weeks after 4 months of sustained response (PR or CR) in the skin, and every 12 weeks thereafter. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy measures • Progression-free survival (PFS). • Complete response rate (CRR). • Time to progression (TTP). • Time to maximal effect in skin (mSWAT). • Proportion of subjects achieving = 50% improvement in mSWAT of at least 28-days duration (ORRI). • Proportion 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. • During the crossover portion of the study: o Proportion of subjects achieving an objective skin response (complete response [CR] or partial response [PR]) of at least 4 months duration (ORR4) using the mSWAT scoring. o Progression-free survival (PFS). o Complete response rate (CRR). o Time to progression (TTP). o Time to maximal effect in skin (mSWAT). o Proportion of subjects achieving = 50% improvement in mSWAT of at least 28-days duration (ORR1). o Proportion of subjects achieving = 50% improvement in mSWAT from baseline at 28 days and at 4 months. o Time to = 50% improvement in mSWAT. o Duration of response in skin (no progression after achieving = 50% improvement in mSWAT). o Change in pruritus medication utilization from baseline and incidence of pruritus medication utilization. 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. • Characterization of anti-drug antibody generation. Pharmacokinetic Evaluation: • Population PK parameters. • During the crossover portion of the study: o Pharmacokinetic Cmax and trough concentration analys | — |
Countries
Austria, Belgium, Canada, France, Germany, Spain, United Kingdom, United States
Contacts
Public ContactSOLAR Clinical Trial Information
miRagen Therapeutics, Inc.
Outcome results
None listed