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MW151-101: First-in-human Study of MW151

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04120233
Recruitment Status : Recruiting
First Posted : October 9, 2019
Last Update Posted : February 19, 2020
Sponsor:
Collaborators:
Duke Clinical Research Institute
National Institute on Aging (NIA)
ImmunoChem Therapeutics, LLC
Information provided by (Responsible Party):
Linda Van Eldik, University of Kentucky

Brief Summary:

MW01-2-151SRM (=MW151), a small molecule, is being developed for the treatment of cognitive disorders. The development program is based on nonclinical evidence that MW151 improves neurocognitive outcomes in animal models of radiation-induced cognitive impairment, Alzheimer's disease, and other central nervous system (CNS) disorders.

The present study will provide safety and pharmacokinetic (PK) information on single ascending doses to support decisions for continued clinical development.


Condition or disease Intervention/treatment Phase
Drug Toxicity Drug: Placebo Drug: MW151, 10mg Drug: MW151, 20mg Drug: MW151, 40mg Drug: MW151, 80mg Drug: MW151, 160mg Phase 1

Detailed Description:

The primary objective of this trial is to assess the safety and tolerability of single ascending doses of MW151 when administered orally to healthy adults.

Subjects will be screened prior to inpatient admission. Subjects will be admitted to the inpatient clinic on the day prior to dosing (Day -1) and will remain in the unit until discharge on Day 3. A follow-up visit will be done on Day 7. A single dose of study drug or placebo will be administered on Day 1. Forty healthy adult male and female subjects will be randomly assigned to one of 5 dose cohorts (8 subjects each). Each subject will receive a single dose of MW151 (10-160mg) or placebo under fasted conditions.

Following a review of safety and tolerability data for the first 24 hours of dosing in each cohort (including reported adverse events (AEs), physical examination findings, clinical laboratory results, vital signs, and electrocardiograms (ECGs), the remaining 6 subjects will be randomized in a 5:1 ratio. Dosing of the remaining subjects in a cohort may proceed after review of sentinel subject safety data collected during the first 24 hours of dosing and determination that no stopping rules are met. The remaining subjects in each cohort will be dosed sequentially, not simultaneously.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose-escalation study.
Masking: Single (Outcomes Assessor)
Masking Description: Data from cohorts will be reviewed in a blinded manner.
Primary Purpose: Other
Official Title: A Phase 1a, Double-Blind, Randomized, Placebo-Controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of MW151 Administered Orally to Healthy Volunteers
Actual Study Start Date : October 22, 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

Arm Intervention/treatment
Placebo Comparator: Placebo
Participants will receive placebo.
Drug: Placebo
Matched placebo administered orally

Experimental: Dose 1
Participants will receive 10 mg of MW151.
Drug: MW151, 10mg
10 mg MW151, 1 x 10mg capsule administered orally

Experimental: Dose 2
Participants will receive 20mg of MW151.
Drug: MW151, 20mg
20 mg MW151, 1 x 20mg capsule administered orally

Experimental: Dose 3
Participants will receive 40mg of MW151.
Drug: MW151, 40mg
40 mg MW151, 2 x 20mg capsule administered orally

Experimental: Dose 4
Participants will receive 80mg of MW151.
Drug: MW151, 80mg
80 mg MW151, 1 x 80mg capsule administered orally

Experimental: Dose 5
Participants will receive 160mg of MW151.
Drug: MW151, 160mg
160 mg MW151, 2 x 80mg capsule administered orally




Primary Outcome Measures :
  1. Percentage of participants experiencing drug-related serious adverse events. [ Time Frame: Seven days ]
    Percentage of participants experiencing drug-related serious adverse events.


Other Outcome Measures:
  1. Maximum Drug Concentration (Cmax) [ Time Frame: Seven days ]
    Peak serum concentration of MW151.

  2. Time to Maximum Drug Concentration (Tmax) [ Time Frame: Seven days ]
    Time required to reach the maximum serum concentration of MW151.

  3. Overall Drug Exposure (AUC) [ Time Frame: Seven days ]
    Overall drug exposure (mg*h/L) determined by calculating the area under the curve (AUC) from a plasma drug concentration-time curve.

  4. Drug Half-Life (T1/2) [ Time Frame: Seven days ]
    Time at which the concentration of MW151 is at half the maximum concentration.

  5. Elimination Rate Constant (Kel) [ Time Frame: Seven days ]
    Fraction of MW151 eliminated per unit of time (mathematical determination).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Willing and able to provide written informed consent
  • In good health as determined by medical history, physical exam, laboratory examinations, ECG, and vital signs.
  • Weight >50kg
  • BMI <34 kg/m2.
  • ECG without clinically significant pathologic abnormalities and with QTcF <450 ms -
  • Systolic BP ≤ 150 mmHg and diastolic BP ≤ 90 mmHg at screening
  • No suicidal ideation, as demonstrated by a score of "0" on the Columbia Suicide Severity Rating Scale (C-SSRS).
  • Women who are neither pregnant (negative pregnancy test) nor nursing, and are either: surgically sterile, postmenopausal with last natural menses greater than 24 months, or premenopausal and agrees to use and acceptable form of birth control during the study and for 1 month after dosing.
  • Men who are surgically sterile or who agree to use a condom with spermicide if sexually active during the study and for 1 month after dosing.
  • Adequate venous access for blood draws.

Exclusion Criteria:

  • Any unstable chronic medical condition requiring interventional treatment that might increase the risk to the subject or confound interpretation of safety observations. Subjects who are considered stable and who have been receiving stable treatment for medical condition for > 3 months may be considered with approval of medical monitor.
  • Evidence of active infection requiring antibiotic therapy within 14 days prior to dosing.
  • Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
  • History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin.
  • Seropositive for human immunodeficiency virus (HIV).
  • History of acute/chronic hepatitis B or C and/or carriers of hepatitis B
  • Clinically significant abnormalities in screening laboratory tests
  • Over-the-counter and herbal medications are prohibited within 10 days prior to study dosing (with exception of calcium/vitamin D supplements and ocular medications at the discretion of the Investigator). Stable doses (> to 3 months of stable dose) of prescription medications are allowed with the approval of the medical monitor (birth control medications are allowed without medical monitor approval). Subjects should not be on non-steroidal anti-inflammatory drugs or immunosuppressive drugs within 10 days prior to dosing.
  • Use of known CYP450 CYP1A2, CYP2D6 or CYP3A4 inhibitors or inducers within 14 days of dosing or planned use during the study.
  • Use of an investigational drug, vaccine, device, or blood product within 3 months prior to dosing in this study.
  • Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs (e.g. small bowel disease, Crohn's disease, celiac disease, or liver disease.)
  • Psychiatric history of current or past psychosis, bi-polar disorder, clinical depression, or anxiety disorder requiring chronic medication within the past 5 years.
  • History of substance abuse including alcohol within the past 5 years.
  • Smoker.
  • Current substance or drug dependence confirmed by positive urine drug screen at screening visit or Day -1 admission.
  • Current alcohol abuse confirmed by positive breathalyzer at screening visit or Day -1 admission.
  • History of serious head injury as determined by the site investigator or designee.
  • Chronic kidney disease (defined as the presence of any degree of proteinuria on urine analysis and/or an eGFR of <60 ml/min using the MDRD formula).
  • Any reason or opinion of the investigator that would prevent the subject from participation in the study.
  • Inability to follow the instructions or an unwillingness to cooperate with study procedures.
  • Has donated more than 500 mL of blood within the last month prior to dosing.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04120233


Contacts
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Contact: Linda J Van Eldik, PhD 859-257-5566 linda.vaneldik@gmail.com

Locations
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United States, North Carolina
Duke Clinical Research Institute Recruiting
Durham, North Carolina, United States, 27705
Contact: Jeffrey T Guptill, MD    919-668-8445    Jeffrey.guptill@duke.edu   
Principal Investigator: Jeffrey T Guptill, MD         
Sponsors and Collaborators
Linda Van Eldik
Duke Clinical Research Institute
National Institute on Aging (NIA)
ImmunoChem Therapeutics, LLC
Investigators
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Principal Investigator: Linda J Van Eldik, PhD University of Kentucky
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Responsible Party: Linda Van Eldik, Director, Sanders-Brown Center on Aging, University of Kentucky
ClinicalTrials.gov Identifier: NCT04120233    
Other Study ID Numbers: Pro00103072, IND143222
R01AG061898 ( U.S. NIH Grant/Contract )
First Posted: October 9, 2019    Key Record Dates
Last Update Posted: February 19, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share IPD at this time.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Linda Van Eldik, University of Kentucky:
cognitive disorder
pharmacokinetics
MW151
MW01-2-151SRM
PK
dose escalation
Additional relevant MeSH terms:
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Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders