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

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

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04120233
Enrollment
40
Registered
2019-10-09
Start date
2019-10-22
Completion date
2021-09-16
Last updated
2022-12-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Drug Toxicity

Keywords

cognitive disorder, pharmacokinetics, MW151, MW01-2-151SRM, PK, dose escalation

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.

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. Healthy adult 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.

Interventions

DRUGPlacebo

Matched placebo administered orally

DRUGMW151, 10mg

10 mg MW151, 1 x 10mg capsule administered orally

DRUGMW151, 20mg

20 mg MW151, 1 x 20mg capsule administered orally

DRUGMW151, 40mg

40 mg MW151, 2 x 20mg capsule administered orally

DRUGMW151, 80mg

80 mg MW151, 1 x 80mg capsule administered orally

DRUGMW151, 160mg

160 mg MW151, 2 x 80mg capsule administered orally

Sponsors

Duke Clinical Research Institute
CollaboratorOTHER
National Institute on Aging (NIA)
CollaboratorNIH
Linda Van Eldik
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)

Masking description

Data from cohorts will be reviewed in a blinded manner.

Intervention model description

Dose-escalation study.

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes

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. * 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.

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Participants Experiencing Drug-related Serious Adverse Events.Seven daysPercentage of participants experiencing drug-related serious adverse events from the start of study drug administration up to 7-day follow-up.

Secondary

MeasureTime frameDescription
Maximum Drug Concentration (Cmax)predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dosePeak serum concentration of MW151.
Time to Maximum Drug Concentration (Tmax)predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-doseTime required to reach the maximum serum concentration of MW151.
Overall Drug Exposure (AUC)predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-doseOverall drug exposure (h\*ng/mL) determined by calculating the area under the curve (AUC) from a plasma drug concentration-time curve.
Drug Half-Life (T1/2)predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-doseTime at which the concentration of MW151 is at half the maximum concentration.
Elimination Rate Constant (Kel)predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-doseFraction of MW151 eliminated per unit of time (mathematical determination).

Countries

United States

Participant flow

Recruitment details

The study was initiated on October 11, 2019 and last follow-up was completed on September 16,2021.

Pre-assignment details

A total of 97 subjects were screened and 40 subjects were randomized.

Participants by arm

ArmCount
Placebo
Participants will receive placebo. Placebo: Matched placebo administered orally
10
Dose 1
Participants will receive 10 mg of MW151. MW151, 10mg: 10 mg MW151, 1 x 10mg capsule administered orally
6
Dose 2
Participants will receive 20mg of MW151. MW151, 20mg: 20 mg MW151, 1 x 20mg capsule administered orally
6
Dose 3
Participants will receive 40mg of MW151. MW151, 40mg: 40 mg MW151, 2 x 20mg capsule administered orally
6
Dose 4
Participants will receive 80mg of MW151. MW151, 80mg: 80 mg MW151, 1 x 80mg capsule administered orally
6
Dose 5
Participants will receive 160mg of MW151. MW151, 160mg: 160 mg MW151, 2 x 80mg capsule administered orally
6
Total40

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005
Overall StudyAdverse Event000010

Baseline characteristics

CharacteristicPlaceboTotalDose 5Dose 4Dose 3Dose 2Dose 1
Age, Continuous34.7 years
STANDARD_DEVIATION 9.4
36.8 years
STANDARD_DEVIATION 8.1
35.2 years
STANDARD_DEVIATION 7.4
40.9 years
STANDARD_DEVIATION 6.4
34.5 years
STANDARD_DEVIATION 8.6
39.3 years
STANDARD_DEVIATION 8.2
37.9 years
STANDARD_DEVIATION 8.3
Body Mass Index (BMI)28.0 kg/m^2
STANDARD_DEVIATION 3.6
27.4 kg/m^2
STANDARD_DEVIATION 3.7
27.6 kg/m^2
STANDARD_DEVIATION 4
27.5 kg/m^2
STANDARD_DEVIATION 4.3
25.8 kg/m^2
STANDARD_DEVIATION 2.6
28.3 kg/m^2
STANDARD_DEVIATION 4.9
26.9 kg/m^2
STANDARD_DEVIATION 3.8
Ethnicity (NIH/OMB)
Hispanic or Latino
3 Participants7 Participants0 Participants1 Participants0 Participants3 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
7 Participants33 Participants6 Participants5 Participants6 Participants3 Participants6 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Height163.3 cm
STANDARD_DEVIATION 5.8
165.9 cm
STANDARD_DEVIATION 8.5
165.1 cm
STANDARD_DEVIATION 4.3
169.3 cm
STANDARD_DEVIATION 7.5
162.5 cm
STANDARD_DEVIATION 1.9
158.0 cm
STANDARD_DEVIATION 7.5
178.1 cm
STANDARD_DEVIATION 8.2
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants0 Participants
Race (NIH/OMB)
Black or African American
4 Participants17 Participants5 Participants2 Participants2 Participants1 Participants3 Participants
Race (NIH/OMB)
More than one race
1 Participants4 Participants0 Participants2 Participants1 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
5 Participants18 Participants1 Participants2 Participants3 Participants4 Participants3 Participants
Region of Enrollment
United States
10 participants40 participants6 participants6 participants6 participants6 participants6 participants
Sex: Female, Male
Female
9 Participants33 Participants6 Participants6 Participants6 Participants6 Participants0 Participants
Sex: Female, Male
Male
1 Participants7 Participants0 Participants0 Participants0 Participants0 Participants6 Participants
Weight74.8 kg
STANDARD_DEVIATION 11.7
75.5 kg
STANDARD_DEVIATION 13.1
75.1 kg
STANDARD_DEVIATION 10.2
79.6 kg
STANDARD_DEVIATION 17.4
68.1 kg
STANDARD_DEVIATION 7.6
70.5 kg
STANDARD_DEVIATION 12.9
85.3 kg
STANDARD_DEVIATION 15.2

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
deaths
Total, all-cause mortality
0 / 100 / 60 / 60 / 60 / 60 / 6
other
Total, other adverse events
6 / 100 / 64 / 63 / 63 / 62 / 6
serious
Total, serious adverse events
0 / 100 / 60 / 60 / 60 / 60 / 6

Outcome results

Primary

Percentage of Participants Experiencing Drug-related Serious Adverse Events.

Percentage of participants experiencing drug-related serious adverse events from the start of study drug administration up to 7-day follow-up.

Time frame: Seven days

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants Experiencing Drug-related Serious Adverse Events.0 percentage of participants
Dose 1Percentage of Participants Experiencing Drug-related Serious Adverse Events.0 percentage of participants
Dose 2Percentage of Participants Experiencing Drug-related Serious Adverse Events.0 percentage of participants
Dose 3Percentage of Participants Experiencing Drug-related Serious Adverse Events.0 percentage of participants
Dose 4Percentage of Participants Experiencing Drug-related Serious Adverse Events.0 percentage of participants
Dose 5Percentage of Participants Experiencing Drug-related Serious Adverse Events.0 percentage of participants
Secondary

Drug Half-Life (T1/2)

Time at which the concentration of MW151 is at half the maximum concentration.

Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose

Population: Placebo: PK parameters for MW151 cannot be analyzed, as they did not receive the study drug.~Dose 2: Data from two participants were excluded for being nonacceptable, and were not analyzed.~Dose 3, 4 and 5: Data from 5 participants in each group were nonacceptable, and were not analyzed.~Non-acceptance data are defined as: R\^2\_adjusted \<0.8 and terminal elimination phase time span \<3 half-lives after Tmax.

ArmMeasureValue (MEAN)Dispersion
Dose 1Drug Half-Life (T1/2)8.2 hourStandard Deviation 1.9
Dose 2Drug Half-Life (T1/2)10.6 hourStandard Deviation 1.4
Dose 3Drug Half-Life (T1/2)8.8 hour—
Dose 4Drug Half-Life (T1/2)10.4 hour—
Dose 5Drug Half-Life (T1/2)10.6 hour—
Secondary

Elimination Rate Constant (Kel)

Fraction of MW151 eliminated per unit of time (mathematical determination).

Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose

Population: Placebo: PK parameters for MW151 cannot be analyzed, as they did not receive the study drug.~Dose 2: Data from two participants were excluded for being nonacceptable, and were not analyzed.~Dose 3, 4 and 5: Data from 5 participants in each group were nonacceptable, and were not analyzed.~Non-acceptance data are defined as: R\^2\_adjusted \<0.8 and terminal elimination phase time span \<3 half-lives after Tmax.

ArmMeasureValue (MEAN)Dispersion
Dose 1Elimination Rate Constant (Kel)0.09 1/hStandard Deviation 0.02
Dose 2Elimination Rate Constant (Kel)0.07 1/hStandard Deviation 0.01
Dose 3Elimination Rate Constant (Kel)0.08 1/h—
Dose 4Elimination Rate Constant (Kel)0.07 1/h—
Dose 5Elimination Rate Constant (Kel)0.07 1/h—
Secondary

Maximum Drug Concentration (Cmax)

Peak serum concentration of MW151.

Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose

Population: The PK population included all subjects who were administered MW151 and had at least 1 quantifiable concentration of MW151 measurement.~One subject in Cohort 4 withdrew prior to the 36h plasma sampling, so that sampling point was excluded from the PK dataset at that timepoint.~PK parameters for MW151 cannot be analyzed in the placebo group, as they did not receive the study drug.

ArmMeasureValue (MEAN)Dispersion
Dose 1Maximum Drug Concentration (Cmax)32.2 ng/mLStandard Deviation 14.6
Dose 2Maximum Drug Concentration (Cmax)132.0 ng/mLStandard Deviation 62.5
Dose 3Maximum Drug Concentration (Cmax)283.0 ng/mLStandard Deviation 244
Dose 4Maximum Drug Concentration (Cmax)361.0 ng/mLStandard Deviation 53.2
Dose 5Maximum Drug Concentration (Cmax)1190.0 ng/mLStandard Deviation 707
Secondary

Overall Drug Exposure (AUC)

Overall drug exposure (h\*ng/mL) determined by calculating the area under the curve (AUC) from a plasma drug concentration-time curve.

Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose

Population: The PK population included all subjects who were administered MW151 and had at least 1 quantifiable concentration of MW151 measurement.~One subject in Cohort 4 withdrew prior to the 36h plasma sampling, so that sampling point was excluded from the PK dataset at that timepoint.~PK parameters for MW151 cannot be analyzed in the placebo group, as they did not receive the study drug.

ArmMeasureValue (MEAN)Dispersion
Dose 1Overall Drug Exposure (AUC)208.0 h*ng/mLStandard Deviation 91.8
Dose 2Overall Drug Exposure (AUC)741.0 h*ng/mLStandard Deviation 168
Dose 3Overall Drug Exposure (AUC)1250.0 h*ng/mLStandard Deviation 453
Dose 4Overall Drug Exposure (AUC)3120.0 h*ng/mLStandard Deviation 1290
Dose 5Overall Drug Exposure (AUC)7590.0 h*ng/mLStandard Deviation 1800
Secondary

Time to Maximum Drug Concentration (Tmax)

Time required to reach the maximum serum concentration of MW151.

Time frame: predose, 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h and 36h post-dose

Population: The PK population included all subjects who were administered MW151 and had at least 1 quantifiable concentration of MW151 measurement.~One subject in Cohort 4 withdrew prior to the 36h plasma sampling, so that sampling point was excluded from the PK dataset at that timepoint.~PK parameters for MW151 cannot be analyzed in the placebo group, as they did not receive the study drug.

ArmMeasureValue (MEAN)Dispersion
Dose 1Time to Maximum Drug Concentration (Tmax)1.8 hoursStandard Deviation 0.4
Dose 2Time to Maximum Drug Concentration (Tmax)1.6 hoursStandard Deviation 0.7
Dose 3Time to Maximum Drug Concentration (Tmax)1.5 hoursStandard Deviation 1.4
Dose 4Time to Maximum Drug Concentration (Tmax)2.3 hoursStandard Deviation 1.4
Dose 5Time to Maximum Drug Concentration (Tmax)2.0 hoursStandard Deviation 1.6

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026