A First-in-Human Study of AV-001 in Healthy Subjects

NCT04737486 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AV001-PK-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1 randomized, double-blind, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) first-in-human study in healthy subjects. Safety and tolerability assessments will be conducted, and blood samples will be taken pre-dose and at several time points post-dose for pharmacokinetic (PK) and pharmacodynamics (PD) analysis.

Conditions

Covid19-associated ARDS; Covid19; ARDS

Keywords

Vascular normalization; Endothelial stability

Outcome Measures

Primary Outcomes (1)

• Participants experiencing drug-related adverse events

  Number of drug-related adverse events as determined by abnormal clinical laboratory tests, vitals signs, continuous blood pressure monitoring and collection (systolic, diastolic, pulse pressure, heart rate and mean arterial pressure), physical exam and ECG parameters

  8 days following a single intravenous dose (SAD) or 8 days following 7 consecutive daily intravenous doses (MAD)

Secondary Outcomes (12)

• Cmax: Maximum plasma AV-001 concentration

  1 day following a single intravenous dose (SAD); 8 days following 7 consecutive daily intravenous doses (MAD)

• Tmax: Time of maximum plasma AV-001 concentration

  1 day following a single intravenous dose (SAD); 8 days ollowing 7 consecutive daily intravenous doses (MAD)

• AUClast: AUC from predose (time 0) to the time of the last quantifiable concentration

  1 day following a single intravenous dose (SAD); 8 days following 7 consecutive daily intravenous doses (MAD)

• AUCinf: AUC from predose (time 0) extrapolated to infinite time

  1 day following a single intravenous dose (SAD); 1 day following first daily intravenous dose (MAD)

• AUCtau: AUC over the dose interval time

  8 days following 7 consecutive daily intravenous doses (MAD)

Study Arms (4)

Single Ascending Dose Cohort 1-4

EXPERIMENTAL

Intervention: AV-001, 6 subjects per cohort will receive single doses of 1.4 µg/kg up to 56 µg/kg of AV-001 by intravenous bolus injection.

Drug: AV-001

Single Ascending Dose Cohort 1-4, Placebo

PLACEBO COMPARATOR

Intervention: Placebo, 2 subjects per cohort will receive single doses of D-PBS placebo by intravenous bolus injection.

Other: Placebo

Multiple Ascending Dose Cohort 1-2

EXPERIMENTAL

Intervention: AV-001, 6 subjects per cohort will receive multiple doses of 1.4 µg/kg/day up to 56 µg/kg/day of AV-001 daily for 7 consecutive days by intravenous bolus injection.

Drug: AV-001

Multiple Ascending Dose Cohort 1-2, Placebo

PLACEBO COMPARATOR

Intervention: Placebo, 2 subjects per cohort will receive multiple doses of D-PBS placebo daily for 7 consecutive days by intravenous bolus injection.

Other: Placebo

Interventions

AV-001 DRUG

AV-001 (mpaBr) Cl for Injection 2.5 mg/mL

Multiple Ascending Dose Cohort 1-2; Single Ascending Dose Cohort 1-4

Placebo OTHER

D-PBS

Multiple Ascending Dose Cohort 1-2, Placebo; Single Ascending Dose Cohort 1-4, Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject voluntarily agrees to participate in this study and signs an Institutional Review Board (IRB) approved informed consent prior to performing any of the Screening Visit procedures
• Males and female subjects of nonchildbearing potential between 18 to 65 years of age, inclusive, at the Screening Visit
• Male subjects must agree to use a highly effective form of contraception (e.g., abstinence, double-barrier methods, have had a vasectomy or have sexual partner(s) of nonchildbearing potential) at the time of the Screening Visit and for 30 days after the dose or last dose of IMP. Male subjects must also agree to not donate sperm for the duration of the study and until 90 days after the dose or last dose of IMP
• Female subjects must be nonpregnant and nonlactating and either surgically sterile (e.g., bilateral tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or postmenopausal for \> 12 months. Postmenopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels ≥ 40 U/mL at the Screening Visit for amenorrheic female subjects
• Non smokers (or other nicotine use) as determined by history (no nicotine use over the past three months) and by negative urine cotinine concentration at the Screening Visit and admission
• Body weight \> 50 kg and \<150 kg at the Screening Visit
• Body mass index (BMI) between 19 and 32 kg/m2, inclusive, at the Screening Visit
• Vital sign measurements at the Screening Visit and on Day 1 within the following ranges (measurements may be repeated once per the discretion of the Principal Investigator):
• Systolic blood pressure: 110 to 139 mmHg
• Diastolic blood pressure: 70 to 89 mmHg
• Pulse rate: 40 to 90 bpm
• Oral body temperature: 35.0°C to 37.5°C A subject should not be included if their standing vital signs (relative to sitting) show findings which, in the opinion of the Principal Investigator, are associated with the clinical manifestation of postural hypotension (i.e., absence of any other cause). These changes include either a \> 20 mmHg decrease in systolic, a \>10 mmHg decrease in DBP, a \> 30 bpm increase in heart rate from sitting to standing or \> 120 bpm
• Healthy, determined by prestudy medical evaluation (medical history, physical examination, vital signs, 12-lead ECG and clinical laboratory evaluations)

You may not qualify if:

• Subject has clinically significant history or evidence of cardiovascular, hematologic, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological or psychiatric disorder(s) as determined by the Principal Investigator or designee
• Subject has any disorder that would interfere with the absorption, distribution, metabolism or excretion of drugs, in the opinion of the Principal Investigator
• Subject has a history of autonomic dysfunction (e.g., a history of fainting, orthostatic hypotension)
• Subject has any concurrent disease or condition that, in the opinion of the Principal Investigator, would make the subject unsuitable for participation in the clinical study
• Subject has history of alcohol and/or illicit drug abuse within 2 years of entry
• Subject has positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (anti-HCV) or human immunodeficiency virus (HIV) type 1 and 2 antibodies
• Subject has positive breath alcohol test for ethanol at the Screening Visit or admission.
• Subject has positive urine drug test at the Screening Visit or admission
• Female subjects are breastfeeding or female subjects with a positive serum pregnancy test at the Screening Visit or admission
• Subject is unwilling to avoid consumption of xanthine containing products (e.g., caffeine in coffee, tea, chocolate) within 48 hours prior to admission until discharge from the clinical site
• Subject is unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to admission until discharge from the clinical site
• Subject has donated blood (\> 500 mL) or blood products within 2 months (56 days) prior to admission
• Subject has used over-the-counter (OTC) medications (including vitamins), 7 days prior to admission or prescription medications or herbal remedies from 14 days prior to admission until the End-of-Study Visit. By exception, paracetamol/acetaminophen ≤ 1000 mg per day and hormonal replacement therapy are permitted
• Subject has participated in a clinical study or used an investigational drug within 30 days or 5 × half lives (whichever is the longer interval) prior to the Screening Visit
• Subject is unwilling to abstain from vigorous exercise from 48 hours prior to admission until the End of Study Visit

Sponsors & Collaborators

• Vasomune Therapeutics, Inc.: lead

Study Sites (1)

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45227, United States

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Leela Vrishabhendra, MD

  Medpace, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single and multiple ascending dose

Study Record Dates

• First Submitted: December 31, 2020
• First Posted: February 3, 2021
• Study Start: December 16, 2020
• Primary Completion: March 10, 2021
• Study Completion: March 10, 2021
• Last Updated: March 24, 2021

Record last verified: 2021-01

Locations

US (1)