Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MRG-110 Following Intradermal Injection in Healthy Volunteers

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose-escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of MRG-110 Following Local Intradermal Injection After Skin Excisional Wound Creation in Normal Healthy Volunteers

MRG-110 is intended to promote the growth of new blood vessels by inhibiting a molecule called miR-92a. MRG-110 is being studied to determine if it can accelerate healing of wounds by improving blood flow into the wound area. The primary objective of this study is to investigate the safety and tolerability of MRG-110 when injected into the skin at the site of a small skin wound in normal healthy volunteers. Another objective is to study the pharmacokinetics of MRG-110 (the movement of a drug into, through and out of the body). Participants in the clinical trial will receive either a single dose or multiple doses of MRG-110 and/or placebo. Blood samples, urine samples and skin biopsies will be collected to measure how MRG-110 is processed by the body, and how the body responds when exposed to MRG-110.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: MRG-110; Drug: Placebo; Drug: MRG-110; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Normal healthy volunteers.
• Females must be of non-childbearing potential.
• If engaged in sexual relations with a female of child-bearing potential, males must be surgically sterile or 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.
• Must have 2 regions on lower back/upper buttocks that are free of striae, scars, tattoos, or other skin pathologies.
• Must have no conditions that could increase risk of abnormal or delayed healing.

Key Exclusion Criteria:

• Clinically significant abnormalities in medical history or physical examination.
• Clinically significant abnormalities in laboratory tests at screening.
• History of cutaneous disorder.
• Hemangioma, history of hemangioblastoma, or other known vascular disorder.
• Positive for bloodborne pathogen (hepatitis B, hepatitis C, HIV).
• Use of an investigational drug or device within 28 days prior to Day 1, or use of an investigational biological or oligonucleotide drug within 90 days of Day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single Ascending Dose - MRG-110; Intradermal injection of MRG-110 at two wound sites and intradermal injection of placebo at two other wound sites	Drug: MRG-110; Single ascending doses of MRG-110; Drug: Placebo; Single doses of placebo; Drug: MRG-110; Multiple ascending doses of MRG-110; Drug: Placebo; Multiple doses of Placebo
PLACEBO_COMPARATOR: Single Ascending Dose - Placebo; Intradermal injection of placebo at four wound sites	Drug: Placebo; Single doses of placebo; Drug: Placebo; Multiple doses of Placebo
EXPERIMENTAL: Multiple Ascending Dose - MRG-110; Intradermal injection of MRG-110 at two wound sites and intradermal injection of placebo at two other wound sites	Drug: MRG-110; Single ascending doses of MRG-110; Drug: Placebo; Single doses of placebo; Drug: MRG-110; Multiple ascending doses of MRG-110; Drug: Placebo; Multiple doses of Placebo
PLACEBO_COMPARATOR: Multiple Ascending Dose - Placebo; Intradermal injection of placebo at four wound sites	Drug: Placebo; Single doses of placebo; Drug: Placebo; Multiple doses of Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.	Up to Day 55

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration vs. time curve (AUC) of MRG-110 following single and repeat doses.	Up to Day 45
Peak plasma concentration (Cmax) of MRG-110 following single and repeat doses	Up to Day 45

Other Outcome Measures

Outcome Measure	Time Frame
Area of granulation tissue formation	Day 11 or Day 18
Histological markers of angiogenesis (such as CD31, ERG, ITGA5)	Day 11 or Day 18
Wound perfusion measured by laser speckle imaging	Up to Day 45
Proportion of wounds closed over time	Up to Day 55

Collaborators and Investigators

• Sponsor: miRagen Therapeutics, Inc.
• Investigators: Study Director: Diana Escolar, MD, miRagen Therapeutics, Inc.

Publications and helpful links

General Publications

• Huang CK, Kafert-Kasting S, Thum T. Preclinical and Clinical Development of Noncoding RNA Therapeutics for Cardiovascular Disease. Circ Res. 2020 Feb 28;126(5):663-678. doi: 10.1161/CIRCRESAHA.119.315856. Epub 2020 Feb 27.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 9, 2018
• Primary Completion (ACTUAL): March 13, 2019
• Study Completion (ACTUAL): March 13, 2019

Study Registration Dates

• First Submitted: July 9, 2018
• First Submitted That Met QC Criteria: July 19, 2018
• First Posted (ACTUAL): July 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 7, 2019
• Last Update Submitted That Met QC Criteria: May 3, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Angiogenesis Inducing Agents; MicroRNAs
• Other Study ID Numbers: MRG110-01-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No