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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Healthy Volunteer

Intervention / Treatment
-----------------
* Drug: MRG-110
* Drug: Placebo
* Drug: MRG-110
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose - MRG-110<br>Intradermal injection of MRG-110 at two wound sites and intradermal injection of placebo at two other wound sites | Drug: MRG-110<br>* Single ascending doses of MRG-110<br>Drug: Placebo<br>* Single doses of placebo<br>|
| Placebo Comparator: Single Ascending Dose - Placebo<br>Intradermal injection of placebo at four wound sites | Drug: Placebo<br>* Single doses of placebo<br>|
| Experimental: Multiple Ascending Dose - MRG-110<br>Intradermal injection of MRG-110 at two wound sites and intradermal injection of placebo at two other wound sites | Drug: MRG-110<br>* Multiple ascending doses of MRG-110<br>Drug: Placebo<br>* Multiple doses of Placebo<br>|
| Placebo Comparator: Multiple Ascending Dose - Placebo<br>Intradermal injection of placebo at four wound sites | Drug: Placebo<br>* Multiple doses of Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Healthy Volunteers, MicroRNAs, Angiogenesis Inducing Agents