Study of the Safety, Tolerability, and PK of MRX-8 Administered Intravenously to HVs in SAD and MAD Cohorts

• ClinicalTrials.gov Identifier: NCT04649541
• Recruitment Status: Recruiting
• First Posted: December 2, 2020
• Last Update Posted: May 21, 2021
• Sponsor: MicuRx
• Collaborators: Biomedical Advanced Research and Development Authority; Wellcome Trust
• Information provided by (Responsible Party): MicuRx

Study Description

Brief Summary:

This Phase 1 study is designed to assess the safety and tolerability of single and multiple intravenous (IV) doses of MRX-8, to assess the pharmacokinetics of MRX-8 and its primary metabolite following single and multiple IV doses, and to measure the elimination of MRX-8 and its metabolite in urine.

Condition or disease	Intervention/treatment	Phase
Safety	Drug: MRX-8; Drug: Placebo	Phase 1

Detailed Description:

This is a first-in-human, randomized, double-blind, placebo-controlled study consisting of 3 parts. Part 1 will evaluate single ascending doses (SAD) of study drug. Part 2 will evaluate multiple ascending doses (MAD) of study drug administered for 7 days. Part 3 will evaluate MAD of study drug administered for 14 days.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Adaptive, Randomized, Double Blind, Placebo Controlled Three Part Study of the Safety, Tolerability, and Pharmacokinetics of MRX-8 Administered Intravenously to Healthy Volunteers in Single Ascending and Multiple Ascending Dose Cohorts
• Actual Study Start Date: November 29, 2020
• Estimated Primary Completion Date: August 30, 2021
• Estimated Study Completion Date: August 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Single intravenous doses of MRX-8; Single escalating doses of MRX-8	Drug: MRX-8; novel semi-synthetic polymyxin B analog.
Placebo Comparator: Single intravenous doses of placebo; Single intravenous doses of placebo to match MRX-8	Drug: Placebo; 5% dextrose in water
Active Comparator: Multiple intravenous doses of MRX-8 for 7 days; Multiple ascending intravenous doses of MRX-8 every 12 hours for 7 days.	Drug: MRX-8; novel semi-synthetic polymyxin B analog.
Placebo Comparator: Multiple intravenous doses of placebo for 7 days; Multiple intravenous doses of placebo every 12 hours for 7 days to match MRX-8.	Drug: Placebo; 5% dextrose in water
Active Comparator: Multiple intravenous doses of MRX-8 for 14 days; Multiple ascending intravenous doses of MRX-8 every 12 hours for 14 days.	Drug: MRX-8; novel semi-synthetic polymyxin B analog.
Placebo Comparator: Multiple intravenous doses of placebo for 14 days; Multiple intravenous doses of placebo every 12 hours for 14 days to match MRX-8.	Drug: Placebo; 5% dextrose in water

Outcome Measures

Primary Outcome Measures :

1. Adverse events [ Time Frame: Pre-dose through 48 hours after the end of infusion on the final infusion of study drug ]
   Symptoms reported by subjects.
2. Clinical laboratory assessment [ Time Frame: Pre-dose through 48 hours after the end of infusion on the final infusion of study drug ]
   Complete blood count
3. Peak Plasma Concentration (Cmax) [ Time Frame: Pre-dose through 48 hours after the end of infusion on the final infusion of study drug ]
   Cmax of MRX-8 and its primary metabolite following single and multiple intravenous doses
4. Time to Peak Plasma Concentration (Tmax) [ Time Frame: Pre-dose through 48 hours after the end of infusion on the final infusion of study drug ]
   Tmax of MRX-8 and its primary metabolite following single and multiple intravenous doses
5. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Pre-dose through 48 hours after the end of infusion on the final infusion of study drug ]
   AUC of MRX-8 and its primary metabolite following single and multiple intravenous doses
6. Vital signs [ Time Frame: Pre-dose through 48 hours after the end of infusion on the final infusion of study drug ]
   Heart rate

Secondary Outcome Measures :

1. Elimination of MRX-8 and its primary metabolite in urine [ Time Frame: At the end of infusion through 24 hours after the end of infusion on the final infusion of study drug ]
   Quantity of measurable MRX-8 and its primary metabolite excreted in urine

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Willing and able to provide written informed consent
• In good general health

Exclusion Criteria:

• Prior participation in a study utilizing a polymyxin or aminoglycoside antibiotic or other nephrotoxic drug within the 12 months prior to study drug administration on Day 1
• Use of tobacco or nicotine products, in any form, within 30 days prior to study drug administration on Day 1
• Venous access considered inadequate for IV infusions, laboratory safety assessments, or PK sample collection
• Underlying hepatic, renal, metabolic, cardiovascular or immunologic disorders

Contacts and Locations

Contacts

Contact: Clinical coordinator; 510-782-2022; info@micurx.com

Locations

United States, Arizona

Celerion; Recruiting

Tempe, Arizona, United States, 85283

Sponsors and Collaborators

MicuRx

Biomedical Advanced Research and Development Authority

Wellcome Trust

More Information

• Responsible Party: MicuRx
• ClinicalTrials.gov Identifier: NCT04649541
• Other Study ID Numbers: MRX8-101
• First Posted: December 2, 2020
• Last Update Posted: May 21, 2021
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No