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

Cutaneous T-Cell Lymphoma/Mycosis Fungoides Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03713320
• Other study ID #: MRG106-11-201
• Secondary ID: 2018-000727-13
• Status: Terminated
• Phase: Phase 2
• Start date: April 2, 2019
• Est. completion date: December 1, 2020

Study information

• Verified date: March 2022
• Source: miRagen Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 37
• Est. completion date: December 1, 2020
• Est. primary completion date: October 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cutaneous T-Cell Lymphoma/Mycosis Fungoides
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Mycoses
• Mycosis Fungoides

Intervention

Drug:
• Cobomarsen
At least weekly doses of cobomarsen (282 mg) throughout study treatment period
• Vorinostat
Daily doses of vorinostat throughout study treatment period

Locations

Country	Name	City	State
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Linear Clinical Research	Nedlands
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	University Clinic UZ Leuven	Leuven
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Jewish General Hospital	Montréal	Quebec
France	Hôpital Saint André, CHU de Bordeaux	Bordeaux
France	Hôpital Saint-Louis	Paris
France	Centre Hospitalier Lyon-Sud	Pierre-Bénite
France	Hôpital Robert Dubré, CHU de Reims	Reims
France	Centre Hospitalier Universitaire de Rouen	Rouen
Italy	Policlinico S. Orsola-Malpighi	Bologna
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milano
Italy	AOU Citta dell Salute e della Scienza di Torino	Torino
Spain	Vall d'Hebron Institute of Oncology	Barcelona
Spain	Fundación Jiménez Diaz	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Consorcio Hospital General Universitario Valencia	Valencia
United Kingdom	University Hospitals of Birmingham NHS Foundation Trust, Queen Elizabeth Hospital	Birmingham
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Guy's and St. Thomas' NHS Foundation Trust, Cancer Center	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	City of Hope	Duarte	California
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Rochester Skin Lymphoma Medical Group	Fairport	New York
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	UCLA	Los Angeles	California
United States	Smilow Cancer Hospital at Yale-New Haven	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Chao Family Comprehensive Cancer Center at University of California, Irvine	Orange	California
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Washington	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
miRagen Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Peak Plasma Concentration (Cmax) of Cobomarsen - First Dose	Peak plasma concentration (Cmax) of cobomarsen after first dose	1, 1.92, 6, 24 and 48 hours post-dose after the first dose
Other	Peak Plasma Concentration (Cmax) of Cobomarsen - Week 5	Peak plasma concentration (Cmax) of cobomarsen after fourth dose (Week 5)	1, 1.92 and 6 hours post-dose after the Week 5 dose
Other	Area Under the Plasma Concentration vs. Time Curve (AUC) of Cobomarsen - Week 5	Area under the curve (AUClast) for cobomarsen plasma concentration versus time curve after the fourth (Week 5) dose	1, 1.92 and 6 hours post-dose after the Week 5 dose
Other	Number of Participants With Anti-drug Antibody Generation	Number of participants who develop antibodies to cobomarsen during treatment	Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Primary	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.	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	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.	Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Secondary	Complete Response Rate	Percentage of subjects with a complete response in the skin based on mSWAT	Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Secondary	Time to Progression	Time from date of randomization until the earliest date of confirmed progression	Date of first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Secondary	Time to Maximal Effect in mSWAT	Time to greatest improvement in mSWAT score	Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Secondary	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	Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Secondary	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	28 days after first dose
Secondary	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	4 months after first dose
Secondary	Time to = 50% Improvement in mSWAT	Time from date of randomization until = 50% improvement in mSWAT score	Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Secondary	Duration of Response in Skin	Duration of response in skin (no progression after achieving = 50% improvement in mSWAT)	Monthly from first dose through interim analysis data cut-off date of 12-Oct-2020, up to 16 months
Secondary	Pruritus Medication Utilization	Change from baseline in number of pruritus medications taken per subject	Date of first dose through end of treatment or interim analysis data cut-off date of 12-Oct-2020, up to 16 months