Clinical Trials /

SOLAR: Efficacy and Safety of Cobomarsen (MRG-106) vs. Active Comparator in Subjects With Mycosis Fungoides

NCT03713320

Description:

The main objective of this clinical trial is to study the efficacy and safety of cobomarsen (also known as MRG-106) for the treatment of cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) subtype. Cobomarsen is designed to inhibit the activity of a molecule called miR-155 that may be important to the growth and survival of MF cancer cells. The study will compare the effects of cobomarsen to vorinostat, a drug that has been approved for the treatment of CTCL in the United States and several other countries. Participants in the clinical trial will be randomly assigned to receive either weekly doses of cobomarsen by injection into a vein or daily oral doses of vorinostat. Participants will continue on their assigned treatment as long as there is no evidence of progression of their cancer. The effects of treatment will be measured based on changes in skin lesion severity, disease-associated symptoms, and quality of life, as well as the length of time that the subject's disease remains stable or improved, without evidence of disease progression. The safety and tolerability of cobomarsen will be assessed based on the frequency and severity of observed side effects. Participants assigned to receive vorinostat who experience progression of their disease during their participation in this study may have the option to be treated with cobomarsen in a separate clinical trial (MRG106-11-203 or PRISM), if they meet the entry criteria for that study.

Related Conditions:
  • Mycosis Fungoides
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: SOLAR: Efficacy and Safety of Cobomarsen (MRG-106) vs. Active Comparator in Subjects With Mycosis Fungoides
  • Official Title: SOLAR: A Phase 2, Randomized, Open-label, Parallel-group, Active Comparator, Multi-center Study to Investigate the Efficacy and Safety of Cobomarsen (MRG-106) in Subjects With Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype

Clinical Trial IDs

  • ORG STUDY ID: MRG106-11-201
  • SECONDARY ID: 2018-000727-13
  • NCT ID: NCT03713320

Conditions

  • Cutaneous T-Cell Lymphoma/Mycosis Fungoides

Interventions

DrugSynonymsArms
CobomarsenMRG-106Cobomarsen
VorinostatVorinostat

Purpose

The main objective of this clinical trial is to study the efficacy and safety of cobomarsen (also known as MRG-106) for the treatment of cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) subtype. Cobomarsen is designed to inhibit the activity of a molecule called miR-155 that may be important to the growth and survival of MF cancer cells. The study will compare the effects of cobomarsen to vorinostat, a drug that has been approved for the treatment of CTCL in the United States and several other countries. Participants in the clinical trial will be randomly assigned to receive either weekly doses of cobomarsen by injection into a vein or daily oral doses of vorinostat. Participants will continue on their assigned treatment as long as there is no evidence of progression of their cancer. The effects of treatment will be measured based on changes in skin lesion severity, disease-associated symptoms, and quality of life, as well as the length of time that the subject's disease remains stable or improved, without evidence of disease progression. The safety and tolerability of cobomarsen will be assessed based on the frequency and severity of observed side effects. Participants assigned to receive vorinostat who experience progression of their disease during their participation in this study may have the option to be treated with cobomarsen in a separate clinical trial (MRG106-11-203 or PRISM), if they meet the entry criteria for that study.

Detailed Description

      Study Design:

      Subjects will be randomly assigned in a 1:1 ratio to receive either cobomarsen or vorinostat.
      A total of 126 subjects (63 per arm) will be enrolled. Cobomarsen will be administered in the
      clinic by 2-hr intravenous infusion on Days 1, 3, 5 and 8, and weekly thereafter. Vorinostat
      will be dispensed to study subjects and taken as a daily oral dose according to the
      manufacturer's labeled dosing instructions. Treatment will continue until the subject becomes
      intolerant, develops clinically significant side effects, progresses, or the trial is
      terminated.
    

Trial Arms

NameTypeDescriptionInterventions
CobomarsenExperimental
  • Cobomarsen
VorinostatActive Comparator
  • Vorinostat

Eligibility Criteria

        Key Inclusion Criteria:

          -  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

        Key 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, defined as documented
             history of B2 and/or B2 staging at screening

          -  Evidence of large cell transformation

          -  Lymph node involvement at screening, unless radiologically or histologically confirmed
             to be nonmalignant

          -  Visceral involvement related to MF at screening
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of subjects achieving an objective response of at least 4 months duration (ORR4)
Time Frame:Up to approximately 36 months (estimated study duration)
Safety Issue:
Description:Based on composite global response criteria including radiological imaging, flow cytometry, and the modified Severity Weighted Assessment Tool (mSWAT).

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:Up to approximately 36 months (estimated study duration)
Safety Issue:
Description:Time from date of randomization until the date of earliest documented progression or death from any cause
Measure:Pruritus Numerical Rating Scale
Time Frame:Daily, up to 6 months, then weekly up to approximately 36 months (estimated study duration)
Safety Issue:
Description:Measures the patient's degree of itch related to mycosis fungoides based on an 11-point scale (from 0-10), with 0 being no itch and 10 being worst imaginable itch.
Measure:Skindex-29 Dermatological Survey
Time Frame:Monthly, up to approximately 36 months (estimated study duration)
Safety Issue:
Description:Measures the effects of skin disease on quality of life based on a 30-item questionnaire. The patient's responses are transformed to a linear scale from 0 to 100 and averaged to determine a subscore in three domains (Symptoms, Emotions and Functioning), as well as a total score. Lower scores indicate a lesser degree of skin disease interference with quality of life.
Measure:Pain Numerical Rating Scale
Time Frame:Daily, up to 6 months, then weekly up to approximately 36 months (estimated study duration)
Safety Issue:
Description:Measures the patient's intensity of pain related to mycosis fungoides based on an 11-point scale (from 0-10), with 0 being no pain and 10 being worst imaginable pain.
Measure:Difference in drug tolerability by Patient Impression of Treatment Side Effects
Time Frame:Weekly, up to approximately 36 months (estimated study duration)
Safety Issue:
Description:
Measure:Duration of composite global response for responding subjects
Time Frame:Up to approximately 36 months (estimated study duration)
Safety Issue:
Description:
Measure:Complete response rate
Time Frame:Up to approximately 36 months (estimated study duration)
Safety Issue:
Description:Based on composite global response criteria including radiological imaging, flow cytometry, and mSWAT.
Measure:Skin disease severity based on modified Severity-weighted Assessment Tool (mSWAT)
Time Frame:Monthly, up to approximately 36 months (estimated study duration)
Safety Issue:
Description:Measures skin disease severity based on the percentage of skin within each body region with patches, plaques, or tumors. Total scores are calculated by adding the total percent for each category of lesion (patch, plaque, or tumor) and multiplying by a weighting factor. Weighted subtotals are added together to obtain the total score. Lower scores indicate a lower degree of skin disease severity.
Measure:Time to progression
Time Frame:Up to approximately 36 months (estimated study duration)
Safety Issue:
Description:Time from date of randomization until the earliest date of confirmed progression.
Measure:Overall survival
Time Frame:Up to approximately 36 months (estimated study duration)
Safety Issue:
Description:Time from date of randomization until date of death from any cause.
Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame:Up to approximately 36 months (estimated study duration)
Safety Issue:
Description:
Measure:Plasma concentration of cobomarsen
Time Frame:From Day 1 to End of Treatment visit, up to approximately 36 months (estimated study duration)
Safety Issue:
Description:Sparse pharmacokinetic samples will be collected for the purpose of population PK model development and analysis of covariate effects.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:miRagen Therapeutics, Inc.

Trial Keywords

  • SOLAR
  • Cutaneous T-cell Lymphoma
  • CTCL
  • Mycosis Fungoides
  • Lymphoma
  • Lymphoma, T-cell
  • Lymphoma, T-cell, cutaneous
  • Lymphoma, Non-Hodgkin
  • Lymphoproliferative Disorders
  • Lymphatic Diseases
  • Immunoproliferative Disorders
  • Immune System Diseases
  • Neoplasms
  • MicroRNAs
  • Vorinostat
  • Histone Deacetylase Inhibitors

Last Updated

December 6, 2019