Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids

A Phase 2, Double-blind, Placebo-Controlled Study to Investigate the Efficacy, Safety and Tolerability of MRG-201 Following Intradermal Injection in Subjects With a History of Keloids

Remlarsen (MRG-201) is designed to mimic the activity of a molecule called miR-29 that decreases the expression of collagen and other proteins that are involved in scar formation. Remlarsen is being studied to determine if it can limit the formation of fibrous scar tissue in certain diseases. The objectives of this study are to investigate the safety and tolerability of remlarsen in subjects with a history of keloid scars, and to investigate the activity of remlarsen in prevention or reduction of keloid formation. Another objective is to study the pharmacokinetics of remlarsen (the movement of a drug into, through and out of the body). A group of 12-16 study volunteers will undergo two small skin biopsies in the upper back/shoulder region that will be closed with sutures. One biopsy site will be injected with up to 6 doses of remlarsen over a period of 2 weeks and the second site will be injected similarly with a placebo solution. Participants will be monitored for keloid formation at the two biopsy sites, for signs or symptoms of adverse effects on the body, and for the levels of remlarsen in the blood over time. A second 2-week cycle of treatment may be administered if there are signs that a keloid may be forming at one or both biopsy sites. Subjects will be followed for about 1 year following their final course of treatment to assess the long-term safety of remlarsen and the potential for later appearance of a keloid scar. Additional groups of subjects may be enrolled to test lower doses of remlarsen or an extended dosing schedule.

Study Overview

• Status: Completed
• Conditions: Keloid
• Intervention / Treatment: Drug: Remlarsen; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Aventura, Florida, United States, 33180
      • Center for Clinical and Cosmetic Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Texas
    • College Station, Texas, United States, 77845
      • J & S Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Must provide written informed consent.
• Females must not be pregnant, or lactating, and have negative pregnancy tests.
• Study candidates should be likely to form keloids in the upper back/shoulder area after punch biopsy based on a history of a high frequency of keloid formation (≥ 10 keloids) or a history of large keloids (≥ 4 cm).
• Subjects should not anticipate requiring systemic corticosteroids during the study.
• Must have area in upper back/shoulder region free of keloids, acne, striae, or other skin pathologies or complications.
• Female subjects of childbearing potential or male subjects engaged in sexual relations with a female of childbearing potential must be willing to use a highly effective method of contraception throughout their study participation and for at least 6 months after the last dose of study drug.

Key Exclusion Criteria:

• Clinically significant abnormalities in medical history or physical exam that, in the opinion of the Investigator, would make the subject unsuitable for inclusion in the study.
• History of genetic disorders that predispose to keloids (e.g. Ehlers-Danlos syndrome, Ullrich congenital muscular dystrophy, etc.).
• History of renal or liver dysfunction or evidence of renal or liver dysfunction at screening.
• Evidence of clinically significant anemia, neutropenia, or thrombocytopenia at screening.
• History of bleeding diathesis or coagulopathy.
• Active or uncontrolled infection at screening or baseline.
• Recent history of alcoholism, drug abuse or illicit drugs (within the last year), and agreement to refrain from using illicit drugs throughout the study.
• Positive for bloodborne pathogen (HBV, HCV, HIV) at screening.
• Prior malignancies within the past 3 years (allowing squamous cell and basal cell carcinomas that have been successfully treated).
• Use of systemic steroids within 4 weeks of the Baseline visit or local use of steroids within 1 week of the Baseline visit.
• Use of an investigational small molecule drug within 30 days of the baseline visit or use of an investigational oligonucleotide or biologic drug within 90 days of the baseline visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remlarsen - Intradermal; Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject will serve as their own simultaneous control.	Drug: Remlarsen; Intradermal injection at site of one excisional wound; Other Names: MRG-201
Placebo Comparator: Placebo - Intradermal; Six doses remlarsen (5.3 mg) over a period of 2 weeks at the site of one excisional skin wound and six doses Placebo over the same period at the site of a second excisional skin wound. Each subject will serve as their own simultaneous control.	Drug: Placebo; Intradermal injection at site of second excisional wound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 24 Weeks	The percentage of subjects with confirmed keloid formation at treated versus untreated lesions at 24 weeks (± 7 days) after first dose, analyzed using the modified Vancouver Scar Scale which reports a cumulative score based on subscores for vascularity, pliability and height.	24 weeks (± 7 days) from first dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Improvement, Defined as no Confirmed Keloid Formation in the Treated Lesion vs. Confirmed Keloid Formation in the Untreated Lesion.	Percentage of subjects with improvement at 24 weeks (± 7 days), defined as no confirmed keloid formation in the treated lesion vs. confirmed keloid formation in the untreated lesion, based on assessment using the modified Vancouver Scar Scale which reports a cumulative score based on subscores for vascularity, pliability and height.	24 weeks (± 7 days) from first dose
Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 52 Weeks	The percentage of subjects with confirmed keloid formation at treated versus untreated lesions at 52 weeks (± 7 days) after first dose, analyzed using the modified Vancouver Scar Scale which reports a cumulative score based on subscores for vascularity, pliability and height.	52 weeks (± 7 days) from first dose
Time to Keloid Formation	Time to first confirmed keloid formation	First dose to 365 days
Volume of Keloid at 24 Weeks		24 weeks from first dose
Volume of Keloid at 52 Weeks		52 weeks from first dose
Area Under the Plasma Concentration vs. Time Curve (AUC) of Remlarsen - Single Dose	Area under the curve (AUClast) for remlarsen + active metabolites (total active drug) after a single dose	First dose to 24 hours post-dose
Peak Plasma Concentration (Cmax) of Remlarsen - Single Dose	Peak plasma concentration (Cmax) of remlarsen + active metabolites (total active drug) after first dose	First dose to 24 hours post-dose
Area Under the Plasma Concentration vs. Time Curve (AUC) of Remlarsen - Multi-dose	Area under the curve (AUClast) for remlarsen + active metabolites (total active drug) after multiple doses	First dose to up to 13 days post-dose
Peak Plasma Concentration (Cmax) of Remlarsen - Multi-dose	Peak plasma concentration (Cmax) of remlarsen + active metabolites (total active drug) after multiple doses	Dosing on Day 10 or Day 12 through 24 hours post-dose

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2018
• Primary Completion (Actual): June 24, 2020
• Study Completion (Actual): June 24, 2020

Study Registration Dates

• First Submitted: July 6, 2018
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): August 18, 2021
• Last Update Submitted That Met QC Criteria: July 19, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Wound healing; Keloid; MicroRNAs
• Additional Relevant MeSH Terms: Pathologic Processes; Connective Tissue Diseases; Fibrosis; Cicatrix; Collagen Diseases; Keloid
• Other Study ID Numbers: MRG201-30-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No