PRISM: Efficacy and Safety of Cobomarsen (MRG-106) in Subjects With Mycosis Fungoides Who Have Completed the SOLAR Study

Cutaneous T-Cell Lymphoma/Mycosis Fungoides Clinical Trial

— PRISM  

Official title:

PRISM: An Open-label, Multi-Center Extension Study to Investigate the Efficacy and Safety of Cobomarsen (MRG-106) Following Systemic Treatment in Subjects With Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype, Who Have Completed the SOLAR Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03837457
• Other study ID #: MRG106-11-203
• Secondary ID: 2018-003748-22
• Status: Terminated
• Phase: Phase 2
• Start date: October 1, 2019
• Est. completion date: July 27, 2020

Study information

• Verified date: November 2020
• 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 in subjects who have confirmed disease progression following treatment with vorinostat in the SOLAR clinical study (MRG106-11-201). 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 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.

Description:

Study Design:

Up to 60 subjects are expected to be enrolled after discontinuation from the SOLAR clinical study (MRG106-11-201). Cobomarsen will be administered in the clinic by 2-hr intravenous infusion on Days 1, 3, 5 and 8, and weekly thereafter. Treatment will continue until the subject becomes intolerant, develops clinically significant side effects, progresses, or the trial is terminated.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: July 27, 2020
• Est. primary completion date: July 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Must have participated in the comparator arm of the SOLAR clinical trial and completed the study (confirmed disease progression).

Key Exclusion Criteria:

• 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.

• Visceral involvement related to MF at screening.

• Unresolved toxicities from prior vorinostat treatment, defined as having not resolved to CTCAE v5.0 grade 0 or 1.

• Any CTCL systemic therapy after completion of the SOLAR study and prior to Day 1 for PRISM.

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 intravenous infusions of cobomarsen (282 mg) throughout study treatment period

Locations

Country	Name	City	State
Belgium	University Hospital Leuven	Leuven
France	Hopital Saint Andre, CHU de Bordeaux	Bordeaux
France	Hopital Saint-Louis	Paris
France	Hopital Charles Nicolle, CHU de Rouen	Rouen
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The Ohio State University and Wexner Medical Center	Columbus	Ohio
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Washington/Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
miRagen Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with anti-drug antibody generation		Up to approximately 36 months (estimated study duration)
Primary	Proportion of subjects achieving an objective response of at least 4 months duration (ORR4)	Based on composite global response criteria including radiological imaging, flow cytometry, and the modified Severity Weighted Assessment Tool (mSWAT).	Up to approximately 36 months (estimated study duration)
Secondary	Progression-free survival	Time from date of first dose of cobomarsen until the date of earliest documented progression or death from any cause.	Up to approximately 36 months (estimated study duration)
Secondary	Pruritis Numerical Rating Scale	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.	Daily for up to 6 months, then weekly up to approximately 36 months (estimated study duration)
Secondary	Skindex-29 Dermatological Survey	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.	Monthly, up to approximately 36 months (estimated study duration)
Secondary	Pain Numerical Rating Scale	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.	Daily, for up to 6 months, then weekly up to approximately 36 months (estimated study duration)
Secondary	Difference in drug tolerability by Patient Impression of Treatment Side Effects		Weekly, up to approximately 36 months (estimated study duration)
Secondary	Duration of composite global response for responding subjects		Up to approximately 36 months (estimated study duration)
Secondary	Complete response rate	Based on composite global response criteria including radiological imaging, flow cytometry, and mSWAT.	Up to approximately 36 months (estimated study duration)
Secondary	Skin disease severity based on modified Severity-weighted Assessment Tool (mSWAT)	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.	Monthly, up to approximately 36 months (estimated study duration)
Secondary	Time to progression	Time from date of first dose of cobomarsen until the earliest date of confirmed progression.	Up to approximately 36 months (estimated study duration)
Secondary	Overall survival	Time from date of first dose of cobomarsen until the date of death from any cause.	Up to approximately 36 months (estimated study duration)
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0		Up to approximately 36 months (estimated study duration)
Secondary	Plasma concentration of cobomarsen	Sparse pharmacokinetic samples will be collected to monitor for accumulation of cobomarsen.	Day 1, Day 29 and monthly or every other month thereafter until End of Treatment visit, up to approximately 36 months (estimated study duration)