Clinical trial NCT06105528: A Phase 1a Study of PMN310 In Healthy Volunteers
Official title: A Phase 1a, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of PMN310 Infusions in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Lead sponsor: ProMis Neurosciences, Inc
Sponsor class: INDUSTRY
First posted: 2023-10-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Female subjects of non-childbearing potential must have evidence from their medical history indicating that they are not of childbearing potential.
3. Any non-vasectomized male subjects must agree to use barrier contraceptives (male or female partner condom, diaphragm, cervical cap, sponges) plus spermicide.
4. Medically healthy with no clinically significant or relevant abnormalities in medical history, physical exam, vital signs, ECG, or laboratory evaluations.
5. Has provided written informed consent.
6. Body mass index is between 18 and 32 kg/m2 (inclusive).
7. Screening MRI normal.

Exclusion Criteria:

1. Clinically significant 12-lead ECG abnormality at Screening.
2. Systolic blood pressure \> 150 bpm or diastolic blood pressure \> 90 bpm at Screening.
3. Experienced a significant systemic illness within 30 days of the first dose of study drug.
4. 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.
5. Currently using any medication except for acetaminophen as needed for miscellaneous aches and pains.
6. History of alcohol abuse and/or illicit drug use within 12 months prior dosing or a smoking history (use of tobacco products).
7. Unwilling to refrain from ingesting alcohol within the limits required by the Study.
8. Positive urine drug screen.
9. History of prior malignancy.
10. 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.
11. Donated blood or blood products (e.g., plasma, platelets) within 28 days prior to first dose.
12. Received an investigational agent within the last 30 days or 5 half-lives (if known) prior to Screening, whichever is longer.
13. Contraindication to brain venipuncture, MRI or LP.
14. Indication of potential suicidality risk as identified by the following Columbia-Suicide Severity Rating Scale (C SSRS).

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events
timeFrame: 85 days
measure: Incidence of clinically significant abnormal findings in laboratory assessments (hematology, serum clinical chemistry, and urinalysis)
timeFrame: 85 days
measure: Incidence of clinically significant abnormal findings in physical examinations including neurological examinations
timeFrame: 85 days
measure: Incidence of clinically significant abnormal findings in vital signs (supine Blood Pressure (BP), pulse, respiratory rate and oral body temperature)
timeFrame: 85 days
measure: Incidence of clinically significant abnormal findings in 12 Lead electrocardiogram (ECG)
timeFrame: 85 days
Secondary outcomes:
measure: Pharmacokinetic properties of PMN310 in Serum
timeFrame: 85 days with an optional assessment at Day 120
measure: Pharmacokinetic properties of PMN310 in CSF
timeFrame: 85 days
Other outcomes:
measure: Immunogenicity of PMN310 - anti-drug antibodies (ADAs) in serum
timeFrame: 85 days with an optional assessment at Day 120
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, LLC
state: Florida
city: Columbus
country: United States
facility: Ohio Clinical Trials
state: Ohio
Study officials:
affiliation: Clnical Pharmacology of Miami
name: Alfredo Fernandez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clnical Pharmacology of Miami
name: Alexander N Prezioso, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio Clinical Trials
name: Angela Eakin, MD
role: PRINCIPAL_INVESTIGATOR
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