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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03713320
Recruitment Status : Terminated (The study was terminated early for business reasons, and not due to concerns regarding safety or lack of efficacy.)
First Posted : October 19, 2018
Results First Posted : April 8, 2022
Last Update Posted : April 8, 2022
Sponsor:
Information provided by (Responsible Party):
miRagen Therapeutics, Inc.

Brief Summary:

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, 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 an open-label, crossover arm of the same study if they meet the entry criteria for that part of the study.


Condition or disease Intervention/treatment Phase
Cutaneous T-Cell Lymphoma/Mycosis Fungoides Drug: Cobomarsen Drug: Vorinostat Phase 2

Detailed Description:

Study Design:

Subjects will be randomly assigned in a 1:1 ratio to receive either cobomarsen or vorinostat. Approximately 126 subjects (63 per arm) are expected to 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. An interim analysis will be conducted after approximately 40 subjects have been followed for a minimum of approximately 6 months. Enrollment will be suspended until the completion of the interim analysis.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 2, 2019
Actual Primary Completion Date : October 12, 2020
Actual Study Completion Date : December 1, 2020


Arm Intervention/treatment
Experimental: Cobomarsen
Cobomarsen will be administered by intravenous 2-hour infusion at a dose of 282 mg on Days 1, 3, 5, 8, and weekly thereafter
Drug: Cobomarsen
At least weekly doses of cobomarsen (282 mg) throughout study treatment period
Other Name: MRG-106

Active Comparator: Vorinostat
Vorinostat will be administered orally at a dose of 400 mg (four 100-mg capsules) once daily with food, at approximately the same time each day.
Drug: Vorinostat
Daily doses of vorinostat throughout study treatment period




Primary Outcome Measures :
  1. Percentage of Subjects Achieving an Objective Skin Response of at Least 4 Months Duration (ORR4) [ Time Frame: Date of first dose through the earlier of last study visit or interim analysis data cut-off date of 12-Oct-2020, up to 16 months ]
    ORR4 is the percentage of subjects with a complete response (CR) or partial response (PR) in the skin for 4 consecutive months confirmed by repeat assessments no less than 28 days (± 3 days) later. The modified Severity Weighted Assessment Tool (mSWAT) is used to measure skin disease severity based on the percentage of body surface area (BSA) with patches, plaques, or tumors. Total scores are calculated by multiplying the BSA percentage for each category of lesion (patch, plaque, or tumor) by a weighting factor and adding the three sub-scores. Lower scores indicate a lower degree of skin disease severity. CR corresponds to 100% clearance of skin lesions present at baseline (mSWAT score of 0). PR corresponds to 50-99% clearance of skin disease present at baseline (at least 50% reduction in mSWAT score), without new tumors.


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months ]
    Time from date of randomization until the date of earliest documented progression or death from any cause. The duration of PFS was censored at the date of the last mSWAT assessment if the subject was alive and had no documented progression. Disease progression in the skin is defined as ≥ 25% increase in mSWAT score from baseline or, in participants with complete or partial response, increase in mSWAT score of greater than the sum of the nadir plus 50% baseline score.

  2. Complete Response Rate [ Time Frame: Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months ]
    Percentage of subjects with a complete response in the skin based on mSWAT

  3. Time to Progression [ Time Frame: Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months ]
    Time from date of randomization until the earliest date of confirmed progression

  4. Time to Maximal Effect in mSWAT [ Time Frame: Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months ]
    Time to greatest improvement in mSWAT score

  5. Objective Response Rate in the Skin of at Least 28-days Duration (ORR1) [ Time Frame: Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months ]
    Percentage of participants achieving ≥ 50% improvement in mSWAT of at least 28-days duration

  6. Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 28 Days [ Time Frame: 28 days after first dose ]
    Percentage of subjects achieving ≥ 50% improvement from baseline in mSWAT at 28 days after first dose

  7. Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 4 Months [ Time Frame: 4 months after first dose ]
    Percentage of subjects achieving ≥ 50% improvement from baseline in mSWAT at 4 months after first dose

  8. Time to ≥ 50% Improvement in mSWAT [ Time Frame: Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months ]
    Time from date of randomization until ≥ 50% improvement in mSWAT score

  9. Duration of Response in Skin [ Time Frame: Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months ]
    Duration of response in skin (no progression after achieving ≥ 50% improvement in mSWAT)

  10. Pruritus Medication Utilization [ Time Frame: Date of first dose through end of treatment or interim analysis data cut-off date of 12-Oct-2020, up to 16 months ]
    Change from baseline in number of pruritus medications taken per subject


Other Outcome Measures:
  1. Peak Plasma Concentration (Cmax) of Cobomarsen - First Dose [ Time Frame: 1, 1.92, 6, 24 and 48 hours post-dose after the first dose ]
    Peak plasma concentration (Cmax) of cobomarsen after first dose

  2. Peak Plasma Concentration (Cmax) of Cobomarsen - Week 5 [ Time Frame: 1, 1.92 and 6 hours post-dose after the Week 5 dose ]
    Peak plasma concentration (Cmax) of cobomarsen after fourth dose (Week 5)

  3. Area Under the Plasma Concentration vs. Time Curve (AUC) of Cobomarsen - Week 5 [ Time Frame: 1, 1.92 and 6 hours post-dose after the Week 5 dose ]
    Area under the curve (AUClast) for cobomarsen plasma concentration versus time curve after the fourth (Week 5) dose

  4. Number of Participants With Anti-drug Antibody Generation [ Time Frame: Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months ]
    Number of participants who develop antibodies to cobomarsen during treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03713320


Locations
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Sponsors and Collaborators
miRagen Therapeutics, Inc.
Investigators
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Study Director: Diana M. Escolar, MD, FAAN miRagen Therapeutics, Inc.
  Study Documents (Full-Text)

Documents provided by miRagen Therapeutics, Inc.:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: miRagen Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03713320    
Other Study ID Numbers: MRG106-11-201
2018-000727-13 ( EudraCT Number )
First Posted: October 19, 2018    Key Record Dates
Results First Posted: April 8, 2022
Last Update Posted: April 8, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by miRagen Therapeutics, Inc.:
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
Additional relevant MeSH terms:
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Mycoses
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Mycosis Fungoides
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Bacterial Infections and Mycoses
Infections
Vorinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action