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

• Sponsor: miRagen Therapeutics, Inc.
• Information provided by (Responsible Party): miRagen Therapeutics, Inc.

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, 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.

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. 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	126 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 :	September 12, 2018
Estimated Primary Completion Date :	October 2020
Estimated Study Completion Date :	September 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cobomarsen; At least weekly doses of cobomarsen throughout study treatment period	Drug: Cobomarsen; Intravenous infusion; Other Name: MRG-106
Active Comparator: Vorinostat; Daily doses of vorinostat throughout study treatment period	Drug: Vorinostat; Oral capsules

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Progression-free survival [ Time Frame: Up to approximately 36 months (estimated study duration) ]
   Time from date of randomization until the date of earliest documented progression or death from any cause
2. Pruritus Numerical Rating Scale [ Time Frame: Daily, up to 6 months, then weekly up to approximately 36 months (estimated study duration) ]
   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.
3. Skindex-29 Dermatological Survey [ Time Frame: Monthly, up to approximately 36 months (estimated study duration) ]
   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.
4. Pain Numerical Rating Scale [ Time Frame: Daily, up to 6 months, then weekly up to approximately 36 months (estimated study duration) ]
   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.
5. Difference in drug tolerability by Patient Impression of Treatment Side Effects [ Time Frame: Weekly, up to approximately 36 months (estimated study duration) ]
6. Duration of composite global response for responding subjects [ Time Frame: Up to approximately 36 months (estimated study duration) ]
7. Complete response rate [ Time Frame: Up to approximately 36 months (estimated study duration) ]
   Based on composite global response criteria including radiological imaging, flow cytometry, and mSWAT.
8. Skin disease severity based on modified Severity-weighted Assessment Tool (mSWAT) [ Time Frame: Monthly, up to approximately 36 months (estimated study duration) ]
   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.
9. Time to progression [ Time Frame: Up to approximately 36 months (estimated study duration) ]
   Time from date of randomization until the earliest date of confirmed progression.
10. Overall survival [ Time Frame: Up to approximately 36 months (estimated study duration) ]
    Time from date of randomization until date of death from any cause.
11. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: Up to approximately 36 months (estimated study duration) ]
12. Plasma concentration of cobomarsen [ Time Frame: From Day 1 to End of Treatment visit, up to approximately 36 months (estimated study duration) ]
    Sparse pharmacokinetic samples will be collected for the purpose of population PK model development and analysis of covariate effects.

Other Outcome Measures:

1. Number of participants with anti-drug antibody generation [ Time Frame: Up to approximately 36 months (estimated study duration) ]
2. Change from baseline in Mycosis Fungoides/Sézary Syndrome Cutaneous T-cell Lymphoma-Quality of Life (MF/SS CTCL QOL) instrument [ Time Frame: Up to approximately 36 months (estimated study duration) ]
   Measures the impact of CTCL on patients' quality of life based on a 12-item questionnaire. The patient's total scaled score is determined from the sum of the 12 item scores and may range from 62 to 154. Lower scores indicate a lesser degree of CTCL disease interference with quality of life.

Eligibility Criteria

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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

Contacts and Locations

Locations

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United States, California
City of Hope	Recruiting
Duarte, California, United States, 91010
Contact: Lilit Stepanyan 626-256-4673 ext 87761 lstepanyan@coh.org
Principal Investigator: Christiane Querfeld, MD
Chao Family Comprehensive Cancer Center at University of California, Irvine	Recruiting
Orange, California, United States, 92868
Contact: Blake Johnson 714-456-3476 Blakej@uci.edu
Principal Investigator: Lauren Pinter-Brown, MD
United States, Connecticut
Smilow Cancer Hospital at Yale-New Haven	Not yet recruiting
New Haven, Connecticut, United States, 06510
Contact: Francine Foss, MD 203-200-4363 francine.foss@yale.edu
Principal Investigator: Francine Foss, MD
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute	Recruiting
Tampa, Florida, United States, 33612
Contact: Elyce Turba 813-745-1706 elyce.turba@moffitt.org
Principal Investigator: Lubomir Sokol, MD, PhD
United States, Missouri
Washington University School of Medicine	Recruiting
Saint Louis, Missouri, United States, 63108
Contact: Mary Tabacchi, CCRC 314-362-8171 mtabacch@wustl.edu
Principal Investigator: Amy Musiek, MD
United States, New York
Rochester Skin Lymphoma Medical Group	Recruiting
Fairport, New York, United States, 14450
Contact: Shelley Secor-Socha 585-678-9654 ssecorsocha@roclymphoma.com
Principal Investigator: Brian Poligone, MD, PhD
United States, Ohio
The Ohio State University Comprehensive Cancer Center	Recruiting
Columbus, Ohio, United States, 43210
Contact: Alyssa Phillips 614-366-3872 Alyssa.Phillips@osumc.edu
Principal Investigator: Basem William, MD
Canada, Alberta
Cross Cancer Institute	Not yet recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Principal Investigator: Minakshi Taparia, MD
Canada, Ontario
Princess Margaret Cancer Centre	Not yet recruiting
Toronto, Ontario, Canada, M5G 2C1
Principal Investigator: Vishal Kukreti, MD
Canada, Quebec
Jewish General Hospital	Not yet recruiting
Montréal, Quebec, Canada, H3T 1E2
Principal Investigator: Kevin Pehr, MD
United Kingdom
University Hospitals of Birmingham NHS Foundation Trust, Queen Elizabeth Hospital	Recruiting
Birmingham, United Kingdom, B15 2TH
Contact: Julia Scarisbrick, MBChB, FRCP, MD +44 121 371 5127 julia.scarisbrick@uhb.nhs.uk
Principal Investigator: Julia Scarisbrick, MBChB, FRCP, MD

Sponsors and Collaborators

miRagen Therapeutics, Inc.

Investigators

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Study Director:	Diana M. Escolar, MD, FAAN	miRagen Therapeutics, Inc.

More Information

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Responsible Party:	miRagen Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT03713320 History of Changes
Other Study ID Numbers:	MRG106-11-201; 2018-000727-13 ( EudraCT Number )
First Posted:	October 19, 2018
Last Update Posted:	April 8, 2019
Last Verified:	January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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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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Lymphoma; Lymphoma, T-Cell; Mycoses; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases	Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Vorinostat; Histone Deacetylase Inhibitors; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action