Clinical trial NCT03601052: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Keloid
Keywords: Keloid
MicroRNAs
Wound healing
Lead sponsor: miRagen Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-26
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Up to 6 cohorts of 12-16 subjects each may be enrolled to study various dose levels and dosing regimens.
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 24 Weeks
timeFrame: 24 weeks (± 7 days) from first dose
Secondary outcomes:
Other outcomes:
measure: Percentage of Subjects With Improvement, Defined as no Confirmed Keloid Formation in the Treated Lesion vs. Confirmed Keloid Formation in the Untreated Lesion.
timeFrame: 24 weeks (± 7 days) from first dose
measure: Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 52 Weeks
timeFrame: 52 weeks (± 7 days) from first dose
measure: Time to Keloid Formation
timeFrame: First dose to 365 days
measure: Volume of Keloid at 24 Weeks
timeFrame: 24 weeks from first dose
measure: Volume of Keloid at 52 Weeks
timeFrame: 52 weeks from first dose
measure: Area Under the Plasma Concentration vs. Time Curve (AUC) of Remlarsen - Single Dose
timeFrame: First dose to 24 hours post-dose
measure: Peak Plasma Concentration (Cmax) of Remlarsen - Single Dose
timeFrame: First dose to 24 hours post-dose
measure: Area Under the Plasma Concentration vs. Time Curve (AUC) of Remlarsen - Multi-dose
timeFrame: First dose to up to 13 days post-dose
measure: Peak Plasma Concentration (Cmax) of Remlarsen - Multi-dose
timeFrame: Dosing on Day 10 or Day 12 through 24 hours post-dose
Locations:
city: Aventura
country: United States
facility: Center for Clinical and Cosmetic Research
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: College Station
country: United States
facility: J & S Studies
state: Texas
Study officials:
affiliation: miRagen Therapeutics, Inc.
name: Diana M Escolar, MD, FAAN
role: STUDY_DIRECTOR
References: