A MAD Study of TT301/MW189 in Healthy Volunteers

Healthy Adult Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02942771
• Other study ID #: TT301/MW189 Phase 1b
• Status: Completed
• Phase: Phase 1
• Start date: March 20, 2017
• Est. completion date: June 4, 2018

Study information

• Verified date: June 2020
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: June 4, 2018
• Est. primary completion date: June 4, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Adult Volunteers

Intervention

Drug:
• 0.075mg/kg TT301/MW189
0.075 mg/kg IV twice daily on Days 1 through 5
• 0.15mg/kg TT301MW189
0.15 mg/kg IV twice daily on Days 1 through 5
• 0.25mg/kg TT301/MW189
0.25 mg/kg IV twice daily on Days 1 through 5
• 0.30mg/kg TT301/MW189
0.30 mg/kg IV twice daily on Days 1 through 5
• Placebo
0.9% sodium chloride

Locations

Country	Name	City	State
United States	Duke Clinical Research Unit 40 Duke Medicine Circle	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Linda Van Eldik	Alzheimer's Association, Duke Clinical Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serious Adverse Events	The number of participants who experienced serious adverse events.	4 weeks
Primary	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	Pharmacokinetics - Cmax	Maximum observed concentration in plasma.	5 days
Secondary	Pharmacokinetics - Tmax	Time to maximum concentration	5 days
Secondary	Pharmacokinetics - AUC	Area under the concentration-time curve	5 days
Secondary	Pharmacokinetics - T1/2	Terminal half-life (T1/2)	5 days
Secondary	Pharmacokinetics - Kel	Elimination rate constant	5 days