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

Primary Purpose

Cutaneous T-Cell Lymphoma/Mycosis Fungoides

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cobomarsen
Vorinostat
Sponsored by
miRagen Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cutaneous T-Cell Lymphoma/Mycosis Fungoides focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The University of Alabama at Birmingham
  • Mayo Clinic
  • City of Hope
  • UCLA
  • Chao Family Comprehensive Cancer Center at University of California, Irvine
  • Smilow Cancer Hospital at Yale-New Haven
  • Mayo Clinic
  • H. Lee Moffitt Cancer Center and Research Institute
  • Dana Farber Cancer Institute
  • Mayo Clinic
  • Washington University School of Medicine
  • Dartmouth Hitchcock Medical Center
  • Rochester Skin Lymphoma Medical Group
  • Columbia University Medical Center
  • Memorial Sloan Kettering Cancer Center
  • The Ohio State University Comprehensive Cancer Center
  • Thomas Jefferson University
  • MD Anderson Cancer Center
  • Inova Schar Cancer Institute
  • University of Washington
  • Concord Repatriation General Hospital
  • Westmead Hospital
  • Linear Clinical Research
  • University Clinic UZ Leuven
  • Cross Cancer Institute
  • Jewish General Hospital
  • Hôpital Saint André, CHU de Bordeaux
  • Hôpital Saint-Louis
  • Centre Hospitalier Lyon-Sud
  • Hôpital Robert Dubré, CHU de Reims
  • Centre Hospitalier Universitaire de Rouen
  • Policlinico S. Orsola-Malpighi
  • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • AOU Citta dell Salute e della Scienza di Torino
  • Vall d'Hebron Institute of Oncology
  • Fundación Jiménez Diaz
  • Hospital Universitario 12 de Octubre
  • Hospital Universitario de Salamanca
  • Consorcio Hospital General Universitario Valencia
  • University Hospitals of Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
  • Beatson West of Scotland Cancer Centre
  • Guy's and St. Thomas' NHS Foundation Trust, Cancer Center
  • The Christie NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cobomarsen

Vorinostat

Arm Description

Cobomarsen will be administered by intravenous 2-hour infusion at a dose of 282 mg on Days 1, 3, 5, 8, and weekly thereafter

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.

Outcomes

Primary Outcome Measures

Percentage of Subjects Achieving an Objective Skin Response of at Least 4 Months Duration (ORR4)
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

Progression-free Survival (PFS)
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.
Complete Response Rate
Percentage of subjects with a complete response in the skin based on mSWAT
Time to Progression
Time from date of randomization until the earliest date of confirmed progression
Time to Maximal Effect in mSWAT
Time to greatest improvement in mSWAT score
Objective Response Rate in the Skin of at Least 28-days Duration (ORR1)
Percentage of participants achieving ≥ 50% improvement in mSWAT of at least 28-days duration
Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 28 Days
Percentage of subjects achieving ≥ 50% improvement from baseline in mSWAT at 28 days after first dose
Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 4 Months
Percentage of subjects achieving ≥ 50% improvement from baseline in mSWAT at 4 months after first dose
Time to ≥ 50% Improvement in mSWAT
Time from date of randomization until ≥ 50% improvement in mSWAT score
Duration of Response in Skin
Duration of response in skin (no progression after achieving ≥ 50% improvement in mSWAT)
Pruritus Medication Utilization
Change from baseline in number of pruritus medications taken per subject

Full Information

First Posted
October 17, 2018
Last Updated
March 15, 2022
Sponsor
miRagen Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03713320
Brief Title
SOLAR: Efficacy and Safety of Cobomarsen (MRG-106) vs. Active Comparator in Subjects With Mycosis Fungoides
Acronym
SOLAR
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated early for business reasons, and not due to concerns regarding safety or lack of efficacy.
Study Start Date
April 2, 2019 (Actual)
Primary Completion Date
October 12, 2020 (Actual)
Study Completion Date
December 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
miRagen Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cutaneous T-Cell Lymphoma/Mycosis Fungoides
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cobomarsen
Arm Type
Experimental
Arm Description
Cobomarsen will be administered by intravenous 2-hour infusion at a dose of 282 mg on Days 1, 3, 5, 8, and weekly thereafter
Arm Title
Vorinostat
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cobomarsen
Other Intervention Name(s)
MRG-106
Intervention Description
At least weekly doses of cobomarsen (282 mg) throughout study treatment period
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Intervention Description
Daily doses of vorinostat throughout study treatment period
Primary Outcome Measure Information:
Title
Percentage of Subjects Achieving an Objective Skin Response of at Least 4 Months Duration (ORR4)
Description
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.
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
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
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.
Time Frame
Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Title
Complete Response Rate
Description
Percentage of subjects with a complete response in the skin based on mSWAT
Time Frame
Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Title
Time to Progression
Description
Time from date of randomization until the earliest date of confirmed progression
Time Frame
Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Title
Time to Maximal Effect in mSWAT
Description
Time to greatest improvement in mSWAT score
Time Frame
Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Title
Objective Response Rate in the Skin of at Least 28-days Duration (ORR1)
Description
Percentage of participants achieving ≥ 50% improvement in mSWAT of at least 28-days duration
Time Frame
Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Title
Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 28 Days
Description
Percentage of subjects achieving ≥ 50% improvement from baseline in mSWAT at 28 days after first dose
Time Frame
28 days after first dose
Title
Percentage of Subjects Achieving ≥ 50% Improvement in mSWAT at 4 Months
Description
Percentage of subjects achieving ≥ 50% improvement from baseline in mSWAT at 4 months after first dose
Time Frame
4 months after first dose
Title
Time to ≥ 50% Improvement in mSWAT
Description
Time from date of randomization until ≥ 50% improvement in mSWAT score
Time Frame
Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Title
Duration of Response in Skin
Description
Duration of response in skin (no progression after achieving ≥ 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
Title
Pruritus Medication Utilization
Description
Change from baseline in number of pruritus medications taken per subject
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
Other Pre-specified Outcome Measures:
Title
Peak Plasma Concentration (Cmax) of Cobomarsen - First Dose
Description
Peak plasma concentration (Cmax) of cobomarsen after first dose
Time Frame
1, 1.92, 6, 24 and 48 hours post-dose after the first dose
Title
Peak Plasma Concentration (Cmax) of Cobomarsen - Week 5
Description
Peak plasma concentration (Cmax) of cobomarsen after fourth dose (Week 5)
Time Frame
1, 1.92 and 6 hours post-dose after the Week 5 dose
Title
Area Under the Plasma Concentration vs. Time Curve (AUC) of Cobomarsen - Week 5
Description
Area under the curve (AUClast) for cobomarsen plasma concentration versus time curve after the fourth (Week 5) dose
Time Frame
1, 1.92 and 6 hours post-dose after the Week 5 dose
Title
Number of Participants With Anti-drug Antibody Generation
Description
Number of participants who develop antibodies to cobomarsen during treatment
Time Frame
Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Diana M. Escolar, MD, FAAN
Organizational Affiliation
miRagen Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
The University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Mayo Clinic
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Chao Family Comprehensive Cancer Center at University of California, Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Smilow Cancer Hospital at Yale-New Haven
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63108
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Rochester Skin Lymphoma Medical Group
City
Fairport
State/Province
New York
ZIP/Postal Code
14450
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
The Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Inova Schar Cancer Institute
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Concord Repatriation General Hospital
City
Concord
State/Province
New South Wales
ZIP/Postal Code
2139
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
NSW 2145
Country
Australia
Facility Name
Linear Clinical Research
City
Nedlands
ZIP/Postal Code
6009
Country
Australia
Facility Name
University Clinic UZ Leuven
City
Leuven
ZIP/Postal Code
B3000
Country
Belgium
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Jewish General Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Hôpital Saint André, CHU de Bordeaux
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Facility Name
Hôpital Saint-Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Centre Hospitalier Lyon-Sud
City
Pierre-Bénite
ZIP/Postal Code
69310
Country
France
Facility Name
Hôpital Robert Dubré, CHU de Reims
City
Reims
ZIP/Postal Code
51100
Country
France
Facility Name
Centre Hospitalier Universitaire de Rouen
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Policlinico S. Orsola-Malpighi
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
AOU Citta dell Salute e della Scienza di Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Vall d'Hebron Institute of Oncology
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Fundación Jiménez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Consorcio Hospital General Universitario Valencia
City
Valencia
ZIP/Postal Code
46014
Country
Spain
Facility Name
University Hospitals of Birmingham NHS Foundation Trust, Queen Elizabeth Hospital
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
Guy's and St. Thomas' NHS Foundation Trust, Cancer Center
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33085815
Citation
Ganguly K, Kishore U, Madan T. Interplay between C-type lectin receptors and microRNAs in cellular homeostasis and immune response. FEBS J. 2021 Jul;288(14):4210-4229. doi: 10.1111/febs.15603. Epub 2020 Nov 7.
Results Reference
derived
PubMed Identifier
32632956
Citation
Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.
Results Reference
derived

Learn more about this trial

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

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