Efficacy, Safety, and Tolerability of Remlarsen (MRG-201) Following Intradermal Injection in Subjects With a History of Keloids
Condition: Keloid
MeSH terms: Keloid
Intervention: Remlarsen; Placebo
Intervention description: Intradermal injection at site of one excisional wound; Intradermal injection at site of second excisional wound
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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.
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Keloid; MicroRNAs; Wound healing

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.