A MAD Study of TT301/MW189 in Healthy Volunteers

A Phase 1b, Double-Blind, Randomized, Placebo-Controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of TT301/MW189 Administered Intravenously to Healthy Volunteers

The purpose of this Study is to find out whether an investigational drug is safe and well tolerated. MW189 is being studied as a possible short-term treatment for people with different types of brain injury. MW189 has previously been given to healthy human volunteers as a single dose, and there were no significant problems or bad effects in people who received the Study drug. However, before it can be tested in people with brain injury, it is important to test MW189 in healthy volunteers when given multiple doses.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Volunteers
• Intervention / Treatment: Drug: 0.075mg/kg TT301/MW189; Drug: 0.15mg/kg TT301MW189; Drug: 0.25mg/kg TT301/MW189; Drug: 0.30mg/kg TT301/MW189; Drug: Placebo

Detailed Description

This is a phase 1b study. Written informed consent will be obtained from each study participant before any study-specific procedures or assessments are done.

At various time points noted below, pharmacokinetic (PK) blood sampling will be performed on study participants.

Throughout the study the investigator will be assessing adverse events and concomitant medication.

On-Study/On-Interventions Evaluations/procedures: Participants will arrive at the Phase 1 unit after fasting a minimum of 10 hours, for admission into the unit and will undergo procedures:

• Medical and medication histories
• Infection screen
• Body temperature
• Vital signs (blood pressure and heart rate)
• Physical examination and weight
• Neurological exam
• Safety laboratory tests (blood and urine)
• Urine pregnancy test (females only)
• Alcohol screening (Breathalyzer)
• Urine drug screen
• Hepatitis B, C and HIV screening
• Randomize: Only participants who meet eligibility requirements will be randomized into the study.

Day 1 - Dosing: A light breakfast will be given prior to dosing. Participants will have the following tests/procedures performed at various time points during the day following confirmation of eligibility.

• 8 electrocardiograms (ECG)
• 8 vital signs (blood pressure and heart rate)
• 1 body temperature
• 12 PK Blood draws
• 2 study drug administrations

Day 2: A light breakfast will be given prior to dosing.

• 8 ECGs
• 8 vital signs (blood pressure and heart rate)
• 1 body temperature
• 1 PK blood draw
• 2 study Drug administration

Day 3: Participants will fast for a minimum of 10 hours. Water is allowed. A Light breakfast will be given before dosing

• 1 safety laboratory tests (blood and urine)
• 1 ECG
• 2 vital signs (blood pressure and heart rate)
• 1 body temperature
• 1 PK blood draw
• 1 neurological examination
• 2 study drug administrations

Day 4: A Light breakfast will be given before dosing

• 2 vital signs (blood Pressure and heart rate)
• 1 body temperature
• 1 PK blood draw
• 2 study drug administrations

Day 5: A Light breakfast will be given before dosing

• 1 ECG
• 2 vital signs (Blood Pressure and heart rate)
• 1 body temperature
• 12 PK blood draw
• 2 study drug administration

Day 6: Participants will fast for a minimum of 10 hours. Water is allowed. A Light breakfast will be given

• 1 safety laboratory test (blood and urine)
• 1 vital sign (Blood pressure and heart rate)
• 1 body temperature
• 1 neurological examination
• 2 PK blood draw

Day 7: A light breakfast will be provided

• 1 vital sign
• 1 body temperature
• 1 PK blood draw

Day 8 (Discharge): Participants will fast for a minimum of 10 hours. Water is allowed. A light breakfast will be offered

• 1 safety laboratory test (blood and urine)
• 1 ECG
• 1 vital sign (blood pressure and heart rate)
• 1 body temperature
• 1 physical examination including weight

• 1 neurological examination

  2 Week Follow-up Visit: Participants will fast for a minimum of 10 hours. Water is allowed.

during this visit participants will have the following tests and procedures performed:

• 1 safety laboratory test (blood and urine)
• 1 ECG
• 1 vital sign (blood pressure and heart rate)
• 1 body temperature

6-8 Week Follow-up Phone Call: Participants will be asked about any adverse events and any medications they may be taking.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Clinical Research Unit 40 Duke Medicine Circle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willingness and capacity to give informed consent
• Is in good health
• Weights 50.0 - 120.0 kg
• Not pregnant
• Must agree to use birth control for 1 week after the last day of study drug administration
• Willingness to comply with protocol requirements, including fasting, alcohol and nicotine restrictions, during the study and is available to complete the study
• Adequate forearm vein access
• No significant dietary restrictions
• Must not have donated blood, platelets, or any other blood components 30 days, or plasma 60 days, prior to consenting. Must also agree not to donate blood, platelets, or any other blood components for 8 weeks after the last dose of study drug

Exclusion Criteria:

• Lactating or is pregnant
• severe ischemic heart disease or congestive heart failure
• Heart attack within the previous 2 years;
• history of stroke or cardiomyopathy;
• significant liver or kidney disease;
• diabetes;
• history of any autoimmune disorder; or a history of chronic infections
• a history of cancer
• has received antibiotic treatment or has undergone a surgical procedure within 30 days of Day 1
• has a history of Hepatitis C, Hepatitis B or tuberculosis (TB)
• has a history of Human Immunodeficiency Virus (HIV)
• a history of alcohol or drug use within the twelve months prior to study drug administration
• has used any immunosuppressants or chronic anti-inflammatory drugs medication including prescription medication, over-the-counter medication, health/herbal supplement or vitamin by any route of administration within 7 days of Day 1
• has donated blood within 30 days of consenting or has donated plasma within 60 days of consenting
• has participated in a clinical trial of an immunosuppressive drug within 6 months of Day 1
• has received an investigational drug, used an investigational device or received an investigational medical procedure within 60 days of Day 1, or concurrent with participation in this study
• has participated in any observational studies, experimental studies of non-investigational drugs, devices, or medical procedures within 30 days of Day 1, or concurrent with participation in this study
• has participated in a previous trial with TT301/MW189
• has a history of unexplained syncope or fainting from the collection of blood; i.e., autonomic dysfunction.
• Lack of ability to understand verbal and/ or written English
• had significant trauma or surgical procedure within 1 month prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - TT301/MW189; TT301/MW189 0.075 mg/kg IV (or matched placebo). Each subject will receive 1 dose level of study drug twice daily (bid) on Days 1 through 5, inclusive	Drug: 0.075mg/kg TT301/MW189; 0.075 mg/kg IV twice daily on Days 1 through 5; Other Names: TT301/MW189
Experimental: Cohort 2 -TT301/MW189; TT301/MW189 0.15 mg/kg IV (or matched placebo). Each subject will receive 1 dose level of study drug twice daily (bid) on Days 1 through 5, inclusive	Drug: 0.15mg/kg TT301MW189; 0.15 mg/kg IV twice daily on Days 1 through 5; Other Names: TT301/MW189
Experimental: Cohort 3- TT301/MW189; TT301/MW189 0.25 mg/kg IV (or matched placebo). Each subject will receive 1 dose level of study drug twice daily (bid) on Days 1 through 5, inclusive	Drug: 0.25mg/kg TT301/MW189; 0.25 mg/kg IV twice daily on Days 1 through 5; Other Names: TT301/MW189
Experimental: Cohort 4- TT301/MW189; TT301/MW189 0.30 mg/kg IV (or matched placebo). Each subject will receive 1 dose level of study drug twice daily (bid) on Days 1 through 5, inclusive	Drug: 0.30mg/kg TT301/MW189; 0.30 mg/kg IV twice daily on Days 1 through 5; Other Names: TT301/MW189
Placebo Comparator: Placebo; No drug intervention.	Drug: Placebo; 0.9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Adverse Events	The number of participants who experienced serious adverse events.	4 weeks
Treatment-Emergent Adverse Events	The number of participants who experienced treatment-emergent adverse events (TEAEs). A TEAE is defined as an adverse event that started during the treatment period.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Cmax	Maximum observed concentration in plasma.	5 days
Pharmacokinetics - Tmax	Time to maximum concentration	5 days
Pharmacokinetics - AUC	Area under the concentration-time curve	5 days
Pharmacokinetics - T1/2	Terminal half-life (T1/2)	5 days
Pharmacokinetics - Kel	Elimination rate constant	5 days

Collaborators and Investigators

• Sponsor: Linda Van Eldik
• Collaborators: Duke Clinical Research Institute; Alzheimer's Association
• Investigators: Study Chair: Linda J. Van Eldik, PhD, University of Kentucky; Principal Investigator: Jeffrey T. Guptill, MD, MA,MHS, Duke University

Publications and helpful links

General Publications

• Van Eldik LJ, Sawaki L, Bowen K, Laskowitz DT, Noveck RJ, Hauser B, Jordan L, Spears TG, Wu H, Watt K, Raja S, Roy SM, Watterson DM, Guptill JT. First-in-Human Studies of MW01-6-189WH, a Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Studies in Healthy Adult Volunteers. Clin Pharmacol Drug Dev. 2021 Feb;10(2):131-143. doi: 10.1002/cpdd.795. Epub 2020 Apr 7.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2017
• Primary Completion (Actual): June 4, 2018
• Study Completion (Actual): June 4, 2018

Study Registration Dates

• First Submitted: October 20, 2016
• First Submitted That Met QC Criteria: October 21, 2016
• First Posted (Estimate): October 24, 2016

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 2, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: TT301/MW189 Phase 1b

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No