Clinical trial NCT03603431: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MRG-110 Following Intradermal Injection in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: Healthy Volunteers
MicroRNAs
Angiogenesis Inducing Agents
Lead sponsor: miRagen Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-27
Enrollment: 42
Sex: ALL
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
timeFrame: Up to Day 55
Secondary outcomes:
measure: Area under the plasma concentration vs. time curve (AUC) of MRG-110 following single and repeat doses.
timeFrame: Up to Day 45
measure: Peak plasma concentration (Cmax) of MRG-110 following single and repeat doses
timeFrame: Up to Day 45
Other outcomes:
measure: Area of granulation tissue formation
timeFrame: Day 11 or Day 18
measure: Histological markers of angiogenesis (such as CD31, ERG, ITGA5)
timeFrame: Day 11 or Day 18
measure: Wound perfusion measured by laser speckle imaging
timeFrame: Up to Day 45
measure: Proportion of wounds closed over time
timeFrame: Up to Day 55
Locations:
city: Lincoln
country: United States
facility: Celerion, Inc.
state: Nebraska
Study officials:
affiliation: miRagen Therapeutics, Inc.
name: Diana Escolar, MD
role: STUDY_DIRECTOR
References:
citation: 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.