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

• ClinicalTrials.gov Identifier: NCT03601052
• Recruitment Status: Completed
• First Posted: July 26, 2018
• Results First Posted: July 19, 2021
• Last Update Posted: August 18, 2021
• Sponsor: miRagen Therapeutics, Inc.
• Information provided by (Responsible Party): miRagen Therapeutics, Inc.

Tracking Information

• First Submitted Date: July 6, 2018
• First Posted Date: July 26, 2018
• Results First Submitted Date: June 28, 2021
• Results First Posted Date: July 19, 2021
• Last Update Posted Date: August 18, 2021
• Actual Study Start Date: June 11, 2018
• Actual Primary Completion Date: June 24, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 19, 2021)

Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 24 Weeks [ Time Frame: 24 weeks (± 7 days) from first dose ]

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.

Original Primary Outcome Measures (submitted: July 17, 2018)

• Proportion of confirmed keloid formation across subjects for treated vs. untreated lesions. [ Time Frame: Up to 365 days ]
• Proportion of subjects with improvement, defined as no confirmed keloid formation in the treated lesion vs. confirmed keloid formation in the untreated lesion. [ Time Frame: Up to 365 days ]
• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: Up to 365 days ]

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: July 17, 2018)

• Area under the plasma concentration vs. time curve (AUC) of MRG-201 [ Time Frame: Up to 27 days ]
• Peak plasma concentration (Cmax) of MRG-201 [ Time Frame: Up to 27 days ]

Current Other Pre-specified Outcome Measures (submitted: July 19, 2021)

• Percentage of Subjects With Improvement, Defined as no Confirmed Keloid Formation in the Treated Lesion vs. Confirmed Keloid Formation in the Untreated Lesion. [ Time Frame: 24 weeks (± 7 days) from first dose ]
  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.
• Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 52 Weeks [ Time Frame: 52 weeks (± 7 days) from first dose ]
  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.
• Time to Keloid Formation [ Time Frame: First dose to 365 days ]
  Time to first confirmed keloid formation
• Volume of Keloid at 24 Weeks [ Time Frame: 24 weeks from first dose ]
• Volume of Keloid at 52 Weeks [ Time Frame: 52 weeks from first dose ]
• Area Under the Plasma Concentration vs. Time Curve (AUC) of Remlarsen - Single Dose [ Time Frame: First dose to 24 hours post-dose ]
  Area under the curve (AUClast) for remlarsen + active metabolites (total active drug) after a single dose
• Peak Plasma Concentration (Cmax) of Remlarsen - Single Dose [ Time Frame: First dose to 24 hours post-dose ]
  Peak plasma concentration (Cmax) of remlarsen + active metabolites (total active drug) after first dose
• Area Under the Plasma Concentration vs. Time Curve (AUC) of Remlarsen - Multi-dose [ Time Frame: First dose to up to 13 days post-dose ]
  Area under the curve (AUClast) for remlarsen + active metabolites (total active drug) after multiple doses
• Peak Plasma Concentration (Cmax) of Remlarsen - Multi-dose [ Time Frame: Dosing on Day 10 or Day 12 through 24 hours post-dose ]
  Peak plasma concentration (Cmax) of remlarsen + active metabolites (total active drug) after multiple doses

Original Other Pre-specified Outcome Measures (submitted: July 17, 2018)

• Time to keloid formation [ Time Frame: Up to 365 days ]
• Volume of keloid [ Time Frame: Up to 365 days ]

Descriptive Information

• Brief Title: Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

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

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment

• Condition: Keloid

Intervention

• Drug: Remlarsen
  Intradermal injection at site of one excisional wound
  Other Name: MRG-201
• Drug: Placebo
  Intradermal injection at site of second excisional wound

Study Arms

• 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.
  Intervention: Drug: Remlarsen
• 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.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 8, 2019): 14
• Original Estimated Enrollment (submitted: July 17, 2018): 12
• Actual Study Completion Date: June 24, 2020
• Actual Primary Completion Date: June 24, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03601052
• Other Study ID Numbers: MRG201-30-201
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: miRagen Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: miRagen Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: miRagen Therapeutics, Inc.
• Verification Date: July 2021