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

NCT03601052 | Completed Phase 2 Results FDA Drug

• 1 other identifier: MRG201-30-201
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Keloid

Keywords

Keloid; MicroRNAs; Wound healing

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Percentage of Subjects With Improvement, Defined as no Confirmed Keloid Formation in the Treated Lesion vs. Confirmed Keloid Formation in the Untreated Lesion.

  24 weeks (± 7 days) from first dose

• Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 52 Weeks

  52 weeks (± 7 days) from first dose

• Time to Keloid Formation

  First dose to 365 days

Study Arms (2)

Remlarsen - Intradermal

EXPERIMENTAL

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

Placebo - Intradermal

PLACEBO COMPARATOR

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

Interventions

Remlarsen DRUG

Intradermal injection at site of one excisional wound

Also known as: MRG-201

Remlarsen - Intradermal

Placebo DRUG

Intradermal injection at site of second excisional wound

Placebo - Intradermal

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• miRagen Therapeutics, Inc.: lead

Study Sites (4)

Center for Clinical and Cosmetic Research

Aventura, Florida, 33180, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

J & S Studies

College Station, Texas, 77845, United States

Location

MeSH Terms

Conditions

Keloid

Condition Hierarchy (Ancestors)

Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Cicatrix; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Regulatory Affairs
• Organization: Viridian Therapeutics (formerly miRagen Therapeutics)

clinicaltrials@viridiantherapeutics.com

720-722-5917

Study Officials

• Diana M Escolar, MD, FAAN

  miRagen Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The treatment administered to each of two wound sites will be randomized (left versus right), such that all subjects will receive both remlarsen and placebo in a double-blinded fashion.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Up to 6 cohorts of 12-16 subjects each may be enrolled to study various dose levels and dosing regimens.

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: July 26, 2018
• Study Start: June 11, 2018
• Primary Completion: June 24, 2020
• Study Completion: June 24, 2020
• Last Updated: August 18, 2021
• Results First Posted: July 19, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)