A Phase 1a Study of PMN310 In Healthy Volunteers

Study Overview
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Brief Summary
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This first in human Phase 1a clinical trial will evaluate the safety, tolerability, and pharmacokinetics of a single IV infusion of PMN310 in healthy volunteers.

Detailed Description
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This randomized, double-blind, placebo-controlled study will evaluate the safety, tolerability and pharmacokinetics of single ascending doses of intravenous PMN310 in healthy adult volunteers. Subjects will be randomly assigned to receive either a single infusion of PMN310 or placebo. After randomization on Day 1, study drug will be administered followed by the collection of safety, tolerability, and PK data. All dose cohorts will have lumbar punctures (LPs) for PK analysis performed on Day 3 and Day 29. Primary PK and CSF data will be obtained from Day 1 to Day 29. Safety and tolerability will be collected at all visits. The study is an 85-day study with one optional follow up assessment at Day 120.

Official Title
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A Phase 1a, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of PMN310 Infusions in Healthy Volunteers

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: PMN310
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 non-childbearing potential must have evidence from their medical history indicating that they are not of childbearing potential. Any non-vasectomized male subjects must agree to use barrier contraceptives (male or female partner condom, diaphragm, cervical cap, sponges) plus spermicide. Medically healthy with no clinically significant or relevant abnormalities in medical history, physical exam, vital signs, ECG, or laboratory evaluations. Has provided written informed consent. Body mass index is between 18 and 32 kg/m2 (inclusive). Screening MRI normal. Exclusion Criteria: Clinically significant 12-lead ECG abnormality at Screening. Systolic blood pressure > 150 bpm or diastolic blood pressure > 90 bpm at Screening. Experienced a significant systemic illness within 30 days of the first dose of study drug. Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures. Currently using any medication except for acetaminophen as needed for miscellaneous aches and pains. History of alcohol abuse and/or illicit drug use within 12 months prior dosing or a smoking history (use of tobacco products). Unwilling to refrain from ingesting alcohol within the limits required by the Study. Positive urine drug screen. History of prior malignancy. Documented history of human immunodeficiency virus (HIV) antibody or tested positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody at Screening. Donated blood or blood products (e.g., plasma, platelets) within 28 days prior to first dose. Received an investigational agent within the last 30 days or 5 half-lives (if known) prior to Screening, whichever is longer. Contraindication to brain venipuncture, MRI or LP. Indication of potential suicidality risk as identified by the following Columbia-Suicide Severity Rating Scale (C SSRS).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: There will be 5 sequential escalating dose cohort groups. Dose groups are 175 mg, 350 mg, 700 mg, 1400 mg and 2800 mg (optional) administered as a single 60-minute infusion.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 PMN310 175mg or placebo<br>PMN310 175mg or placebo administered as a 60-minute infusion. | Drug: PMN310<br>* 60-minute intravenous infusion<br>Drug: Placebo<br>* 60-minute intravenous infusion<br>|
| Experimental: Cohort 2 PMN310 350mg or placebo<br>PMN310 350mg or placebo administered as a 60-minute infusion. | Drug: PMN310<br>* 60-minute intravenous infusion<br>Drug: Placebo<br>* 60-minute intravenous infusion<br>|
| Experimental: Cohort 3 PMN310 700mg or placebo<br>PMN310 700mg or placebo administered as a 60-minute infusion. | Drug: PMN310<br>* 60-minute intravenous infusion<br>Drug: Placebo<br>* 60-minute intravenous infusion<br>|
| Experimental: Cohort 4 PMN310 1400mg or placebo<br>PMN310 1400mg or placebo administered as a 60-minute infusion. | Drug: PMN310<br>* 60-minute intravenous infusion<br>Drug: Placebo<br>* 60-minute intravenous infusion<br>|
| Experimental: Cohort 5 PMN310 2800mg or placebo<br>PMN310 2800mg or placebo administered as a 60-minute infusion. | Drug: PMN310<br>* 60-minute intravenous infusion<br>Drug: Placebo<br>* 60-minute intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events | Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects. | 85 days | 
| Incidence of clinically significant abnormal findings in laboratory assessments (hematology, serum clinical chemistry, and urinalysis) | Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects. | 85 days | 
| Incidence of clinically significant abnormal findings in physical examinations including neurological examinations | Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects. | 85 days | 
| Incidence of clinically significant abnormal findings in vital signs (supine Blood Pressure (BP), pulse, respiratory rate and oral body temperature) | Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects. | 85 days | 
| Incidence of clinically significant abnormal findings in 12 Lead electrocardiogram (ECG) | Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects. | 85 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic properties of PMN310 in Serum | Measure concentration of PMN310 in serum | 85 days with an optional assessment at Day 120 | 
| Pharmacokinetic properties of PMN310 in CSF | Measure concentration of PMN310 in CSF | 85 days |