Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids
Primary Purpose
Keloid
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Remlarsen
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Keloid focused on measuring Keloid, MicroRNAs, Wound healing
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.
Sites / Locations
- Center for Clinical and Cosmetic Research
- Northwestern University
- Henry Ford Health System
- J & S Studies
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Remlarsen - Intradermal
Placebo - Intradermal
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03601052
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
June 11, 2018 (Actual)
Primary Completion Date
June 24, 2020 (Actual)
Study Completion Date
June 24, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
miRagen Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Keloid
Keywords
Keloid, MicroRNAs, Wound healing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Up to 6 cohorts of 12-16 subjects each may be enrolled to study various dose levels and dosing regimens.
Masking
ParticipantInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Remlarsen - Intradermal
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo - Intradermal
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Remlarsen
Other Intervention Name(s)
MRG-201
Intervention Description
Intradermal injection at site of one excisional wound
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intradermal injection at site of second excisional wound
Primary Outcome Measure Information:
Title
Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 24 Weeks
Description
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.
Time Frame
24 weeks (± 7 days) from first dose
Other Pre-specified Outcome Measures:
Title
Percentage of Subjects With Improvement, Defined as no Confirmed Keloid Formation in the Treated Lesion vs. Confirmed Keloid Formation in the Untreated Lesion.
Description
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.
Time Frame
24 weeks (± 7 days) from first dose
Title
Percentage of Subjects With Confirmed Keloid Formation at Treated vs. Untreated Lesions at 52 Weeks
Description
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 Frame
52 weeks (± 7 days) from first dose
Title
Time to Keloid Formation
Description
Time to first confirmed keloid formation
Time Frame
First dose to 365 days
Title
Volume of Keloid at 24 Weeks
Time Frame
24 weeks from first dose
Title
Volume of Keloid at 52 Weeks
Time Frame
52 weeks from first dose
Title
Area Under the Plasma Concentration vs. Time Curve (AUC) of Remlarsen - Single Dose
Description
Area under the curve (AUClast) for remlarsen + active metabolites (total active drug) after a single dose
Time Frame
First dose to 24 hours post-dose
Title
Peak Plasma Concentration (Cmax) of Remlarsen - Single Dose
Description
Peak plasma concentration (Cmax) of remlarsen + active metabolites (total active drug) after first dose
Time Frame
First dose to 24 hours post-dose
Title
Area Under the Plasma Concentration vs. Time Curve (AUC) of Remlarsen - Multi-dose
Description
Area under the curve (AUClast) for remlarsen + active metabolites (total active drug) after multiple doses
Time Frame
First dose to up to 13 days post-dose
Title
Peak Plasma Concentration (Cmax) of Remlarsen - Multi-dose
Description
Peak plasma concentration (Cmax) of remlarsen + active metabolites (total active drug) after multiple doses
Time Frame
Dosing on Day 10 or Day 12 through 24 hours post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Diana M Escolar, MD, FAAN
Organizational Affiliation
miRagen Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Center for Clinical and Cosmetic Research
City
Aventura
State/Province
Florida
ZIP/Postal Code
33180
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
J & S Studies
City
College Station
State/Province
Texas
ZIP/Postal Code
77845
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids
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