A Phase 1, Randomized, Double-blind, Placebo-Controlled, Single-Ascending-Dose Study to Evaluate the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of Intravenous ORT247 in Healthy Volunteers

Orthogonal Neuroscience Inc.1 site in 1 country44 target enrollmentJune 6, 2022

InterventionsORT247 Placebo

DrugsORT247 Placebo

Overview

Phase: Phase 1
Intervention: ORT247
Conditions: Not specified
Sponsor: Orthogonal Neuroscience Inc.
Enrollment: 44
Locations: 1
Primary Endpoint: Number of participants with treatment-emergent adverse events assessed by severity, frequency and causality
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single center, double-blinded, randomized, placebo controlled single ascending dose clinical study, with the primary purpose of evaluating the safety, tolerability, pharmacokinetics (PK), and immunohistochemistry of escalating intravenous doses of ORT247 in healthy volunteers.

Detailed Description

This is a phase 1, first in human, study of ORT247

Registry

clinicaltrials.gov

Start Date

June 6, 2022

End Date

October 24, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Orthogonal Neuroscience Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject voluntarily consents to participate in this study and provides written informed consent before the start of any study-specific procedures
•Male and females, 18 to 65 years of age at time of screening
•Female subjects of childbearing potential must not be breastfeeding and must have no plans to become pregnant during the course of the study through 120 days after infusion of study drug. Female subjects of childbearing potential who are heterosexual must agree to use a method of contraception considered to be highly effective (i.e., results in \<1% failure rate when used consistently and correctly) from screening through 120 days after the last dose of study drug
•Female subjects of non-childbearing potential must have evidence from their medical history indicating that they are not of childbearing potential and must not currently be breastfeeding.
•Any non-vasectomized male subjects must have agreed to use barrier contraceptives plus spermicide for 200 days after dosing.
•Male subjects must agree not to donate sperm for 200 days after dosing
•Female subjects must agree not to preserve eggs (ova) for 120 days after dosing
•Has not participated in a clinical drug study within 30 days of study start, or within 5 half-lives, unless study blind has been broken and the subject was known to be on placebo
•Body mass index of 18-32

Exclusion Criteria

•Contraindication to undergo LP including international normalized ratio (INR) \>1.4 or other coagulopathy, platelet cell count of \<120,000/μL, infection at the desired LP site, current use of anti-coagulant medication except for low dose aspirin, degenerative arthritis, spinal scoliosis, back surgery, suspected increased intracranial pressure on history or neurologic exam, non-communicating hydrocephalus or intracranial mass, or prior history of spinal mass or trauma
•Any significant acute or chronic medical illness
•Any history of cancer within 5 years of enrollment with the exception of resected skin basal cell carcinoma
•Any major surgery within 4 weeks of study drug administration
•Donation of blood or serum \>500 mL to a blood bank or in a clinical study (except screening visit) within 3 months of study drug administration
•Inability to undergo venipuncture or tolerate venous access
•Has smoked or used tobacco products within 3 months before study drug administration
•Positive drug screen for alcohol, drugs of abuse, or tobacco
•Recent (within 6 months of study drug administration) drug or alcohol abuse as defined in Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V), Diagnostic Criteria for Drug and Alcohol Abuse
•Evidence of any clinically significant neurological or psychiatric disorder that could interfere with study assessments as determined by investigator and sponsor

Arms & Interventions

ORT247

Single ascending dose of intravenous ORT247 administered as a infusion over 60 minutes. Subjects enrolled into 1 of 5 planned cohorts will receive 75mg, 150mg, 300mg, 600mg, and 1200mg with dosing being conducted in a staggered fashion, separated by at least 30 minutes of an infusion in one subject and the start of an infusion in another subject.

Intervention: ORT247

Placebo

Single intravenous dose of vehicle with dosing being conducted in a staggered fashion, separated by at least 30 minutes of an infusion in one subject and the start of an infusion in another subject.

Intervention: Placebo

Outcomes

Primary Outcomes

Number of participants with treatment-emergent adverse events assessed by severity, frequency and causality

Time Frame: From enrollment to day 85 or early termination

Secondary Outcomes

Time to maximum observed serum concentration (Tmax)(Before and at end of infusion (0 hours), and 0.5, 1, 2, 4, 8, and 12, 24, 36 and 48 hours after infusion. Additional samples for assessment of serum concentrations were collected on Day 8, 15, 29, 43, 57, 71 and 85/early termination.)
Maximum observed serum concentration (Cmax)(Before and at end of infusion (0 hours), and 0.5, 1, 2, 4, 8, and 12, 24, 36 and 48 hours after infusion. Additional samples for assessment of serum concentrations were collected on Day 8, 15, 29, 43, 57, 71 and 85/early termination.)
Number of subjects developing anti-drug antibodies(From enrollment to day 85 or early termination)
Area under the curve from Time 0 to 168 hours (AUC0-168)(Before and at end of infusion (0 hours), and 0.5, 1, 2, 4, 8, and 12, 24, 36 and 48 hours after infusion. Additional samples for assessment of serum concentrations were collected on Day 8, 15, 29, 43, 57, 71 and 85/early termination.)
Area under the curve from Time 0 to last sampling time (AUC0-t)(Before and at end of infusion (0 hours), and 0.5, 1, 2, 4, 8, and 12, 24, 36 and 48 hours after infusion. Additional samples for assessment of serum concentrations were collected on Day 8, 15, 29, 43, 57, 71 and 85/early termination.)
Area under the curve from Time 0 to infinity (AUC0-∞)(Before and at end of infusion (0 hours), and 0.5, 1, 2, 4, 8, and 12, 24, 36 and 48 hours after infusion. Additional samples for assessment of serum concentrations were collected on Day 8, 15, 29, 43, 57, 71 and 85/early termination.)
Time to clearance (CL) following single i.v. infusion of ORT247(Before and at end of infusion (0 hours), and 0.5, 1, 2, 4, 8, and 12, 24, 36 and 48 hours after infusion. Additional samples for assessment of serum concentrations were collected on Day 8, 15, 29, 43, 57, 71 and 85/early termination.)
Volume of distribution (Vd) following single i.v. infusion of ORT247(Before and at end of infusion (0 hours), and 0.5, 1, 2, 4, 8, and 12, 24, 36 and 48 hours after infusion. Additional samples for assessment of serum concentrations were collected on Day 8, 15, 29, 43, 57, 71 and 85/early termination.)
Terminal half-life (t1/2) following single i.v. infusion of ORT247(Before and at end of infusion (0 hours), and 0.5, 1, 2, 4, 8, and 12, 24, 36 and 48 hours after infusion. Additional samples for assessment of serum concentrations were collected on Day 8, 15, 29, 43, 57, 71 and 85/early termination.)