A Phase 1a Study of PMN310 In Healthy Volunteers

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06105528

Enrollment

Registered

2023-10-27

Start date

2023-11-18

Completion date

2024-07-31

Last updated

2025-07-25

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

Conditions

Healthy Participants

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.

Interventions

DRUGPMN310

60-minute intravenous infusion

DRUGPlacebo

60-minute intravenous infusion

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

Double blind

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.

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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).

Design outcomes

Primary

Measure	Time frame	Description
Incidence of Clinically Significant Abnormal Findings in 12 Lead Electrocardiogram (ECG)	85 days	Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.
Incidence of Treatment Emergent Adverse Events	85 days	Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.
Incidence of Clinically Significant Abnormal Findings in Laboratory Assessments (Hematology, Serum Clinical Chemistry, and Urinalysis)	85 days	Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.
Incidence of Clinically Significant Abnormal Findings in Physical Examinations Including Neurological Examinations	85 days	Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.
Incidence of Clinically Significant Abnormal Findings in Vital Signs (Supine Blood Pressure (BP), Pulse, Respiratory Rate and Oral Body Temperature)	85 days	Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.

Secondary

Measure	Time frame	Description
Summary of Serum Pharmacokinetic Parameters of PMN310 - Cmax	0 to 2040 hours post-dose	Measure concentration of PMN310 in serum
Summary of Serum Pharmacokinetic Parameters of PMN310 - T1/2	0 to 2040 hours post-dose	Measure concentration of PMN310 in serum
Summary of Serum Pharmacokinetic Parameters of PMN310 - Vd	0 to 2040 hours post-dose	Measure concentration of PMN310 in serum
Summary of Serum Pharmacokinetic Parameters of PMN310 - Tmax	0 to 2040 hours post-dose	Measure concentration of PMN310 in serum
Summary of Serum Pharmacokinetic Parameters of PMN310 - AUCinf	0 to 2040 hours post-dose	Measure concentration of PMN310 in serum
Summary of CSF Concentrations of PMN310	Days 3 and 29	Measure concentration of PMN310 in CSF
Summary of Serum Pharmacokinetic Parameters of PMN310 - AUClast	0 to 2040 hours post-dose	Measure concentration of PMN310 in serum
Summary of Serum Pharmacokinetic Parameters of PMN310 - CL	0 to 2040 hours post-dose	Measure concentration of PMN310 in serum

Other

Measure	Time frame	Description
Immunogenicity of PMN310 - Anti-drug Antibodies (ADAs) in Serum	85 days	The number of subjects who developed detectable levels of anti-PMN310 antibodies following a single intravenous dose

Countries

United States

Participant flow

Recruitment details

To evaluate the short-term safety and tolerability of PMN310, each cohort enrolled a sentinel group of 2 subjects who were dosed prior to dosing the remaining 6 subjects in the cohort (5:1, PMN310:placebo).A total of 129 subjects were screened, of whom, 40 subjects were randomized to treatment groups as follows: 6 subjects each in the PMN310 175 mg, 350 mg, 700 mg, 1400 mg, and 2800 mg groups and 2 subjects each in the matching placebo groups for these doses (10 subjects total received placebo).

Participants by arm

Arm	Count
PMN310 175 mg PMN310 175 mg single IV infusion	6
PMN310 350 mg PMN310 350 mg single IV infusion	6
PMN310 700 mg PMN310 700 mg single IV infusion	6
PMN310 1400 mg PMN310 1400 mg single IV infusion	6
PMN310 2800 mg PMN310 2800 mg single IV infusion	6
Placebo Placebo	10
Total	40

Baseline characteristics

Characteristic	PMN310 350 mg	PMN310 700 mg	PMN310 1400 mg	PMN310 2800 mg	Placebo	PMN310 175 mg	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	6 Participants	6 Participants	6 Participants	6 Participants	10 Participants	6 Participants	40 Participants
Age, Continuous	40.50 Years STANDARD_DEVIATION 9.854	46.17 Years STANDARD_DEVIATION 8.589	43.50 Years STANDARD_DEVIATION 8.826	41.67 Years STANDARD_DEVIATION 9.73	42.10 Years STANDARD_DEVIATION 10.671	38.50 Years STANDARD_DEVIATION 10.407	42.08 Years STANDARD_DEVIATION 9.458
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	5 Participants	0 Participants	2 Participants	6 Participants	6 Participants	24 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants	1 Participants	6 Participants	4 Participants	4 Participants	0 Participants	16 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	0 Participants	6 Participants	4 Participants	1 Participants	1 Participants	14 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) White	4 Participants	5 Participants	0 Participants	2 Participants	9 Participants	5 Participants	25 Participants
Region of Enrollment United States	6 Participants	6 Participants	6 Participants	6 Participants	10 Participants	6 Participants	40 Participants
Sex: Female, Male Female	4 Participants	1 Participants	0 Participants	1 Participants	1 Participants	2 Participants	9 Participants
Sex: Female, Male Male	2 Participants	5 Participants	6 Participants	5 Participants	9 Participants	4 Participants	31 Participants

Adverse events

Event type	EG000 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 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 10
other Total, other adverse events	2 / 6	2 / 6	0 / 6	3 / 6	3 / 6	3 / 10
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6	0 / 6	0 / 6	0 / 10

Outcome results

Primary

Incidence of Clinically Significant Abnormal Findings in 12 Lead Electrocardiogram (ECG)

Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.

Time frame: 85 days

Arm	Measure	Value (NUMBER)
PMN310 175 mg	Incidence of Clinically Significant Abnormal Findings in 12 Lead Electrocardiogram (ECG)	0 abnormal findings
PMN310 350 mg	Incidence of Clinically Significant Abnormal Findings in 12 Lead Electrocardiogram (ECG)	0 abnormal findings
PMN310 700 mg	Incidence of Clinically Significant Abnormal Findings in 12 Lead Electrocardiogram (ECG)	0 abnormal findings
PMN310 1400 mg	Incidence of Clinically Significant Abnormal Findings in 12 Lead Electrocardiogram (ECG)	0 abnormal findings
PMN310 2800 mg	Incidence of Clinically Significant Abnormal Findings in 12 Lead Electrocardiogram (ECG)	0 abnormal findings
Placebo	Incidence of Clinically Significant Abnormal Findings in 12 Lead Electrocardiogram (ECG)	0 abnormal findings

Primary

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.

Time frame: 85 days

Arm	Measure	Value (NUMBER)
PMN310 175 mg	Incidence of Clinically Significant Abnormal Findings in Laboratory Assessments (Hematology, Serum Clinical Chemistry, and Urinalysis)	0 participants
PMN310 350 mg	Incidence of Clinically Significant Abnormal Findings in Laboratory Assessments (Hematology, Serum Clinical Chemistry, and Urinalysis)	0 participants
PMN310 700 mg	Incidence of Clinically Significant Abnormal Findings in Laboratory Assessments (Hematology, Serum Clinical Chemistry, and Urinalysis)	0 participants
PMN310 1400 mg	Incidence of Clinically Significant Abnormal Findings in Laboratory Assessments (Hematology, Serum Clinical Chemistry, and Urinalysis)	0 participants
PMN310 2800 mg	Incidence of Clinically Significant Abnormal Findings in Laboratory Assessments (Hematology, Serum Clinical Chemistry, and Urinalysis)	0 participants
Placebo	Incidence of Clinically Significant Abnormal Findings in Laboratory Assessments (Hematology, Serum Clinical Chemistry, and Urinalysis)	0 participants

Primary

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.

Time frame: 85 days

Arm	Measure	Value (NUMBER)
PMN310 175 mg	Incidence of Clinically Significant Abnormal Findings in Physical Examinations Including Neurological Examinations	0 participants
PMN310 350 mg	Incidence of Clinically Significant Abnormal Findings in Physical Examinations Including Neurological Examinations	0 participants
PMN310 700 mg	Incidence of Clinically Significant Abnormal Findings in Physical Examinations Including Neurological Examinations	0 participants
PMN310 1400 mg	Incidence of Clinically Significant Abnormal Findings in Physical Examinations Including Neurological Examinations	0 participants
PMN310 2800 mg	Incidence of Clinically Significant Abnormal Findings in Physical Examinations Including Neurological Examinations	0 participants
Placebo	Incidence of Clinically Significant Abnormal Findings in Physical Examinations Including Neurological Examinations	0 participants

Primary

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.

Time frame: 85 days

Arm	Measure	Value (NUMBER)
PMN310 175 mg	Incidence of Clinically Significant Abnormal Findings in Vital Signs (Supine Blood Pressure (BP), Pulse, Respiratory Rate and Oral Body Temperature)	0 participants
PMN310 350 mg	Incidence of Clinically Significant Abnormal Findings in Vital Signs (Supine Blood Pressure (BP), Pulse, Respiratory Rate and Oral Body Temperature)	0 participants
PMN310 700 mg	Incidence of Clinically Significant Abnormal Findings in Vital Signs (Supine Blood Pressure (BP), Pulse, Respiratory Rate and Oral Body Temperature)	0 participants
PMN310 1400 mg	Incidence of Clinically Significant Abnormal Findings in Vital Signs (Supine Blood Pressure (BP), Pulse, Respiratory Rate and Oral Body Temperature)	0 participants
PMN310 2800 mg	Incidence of Clinically Significant Abnormal Findings in Vital Signs (Supine Blood Pressure (BP), Pulse, Respiratory Rate and Oral Body Temperature)	0 participants
Placebo	Incidence of Clinically Significant Abnormal Findings in Vital Signs (Supine Blood Pressure (BP), Pulse, Respiratory Rate and Oral Body Temperature)	0 participants

Primary

Incidence of Treatment Emergent Adverse Events

Safety and tolerability of PMN310 following a single intravenous dose in healthy subjects.

Time frame: 85 days

Arm	Measure	Group	Value (NUMBER)
PMN310 175 mg	Incidence of Treatment Emergent Adverse Events	Any TESAE	0 participants
PMN310 175 mg	Incidence of Treatment Emergent Adverse Events	Any Severity Grade 3 TEAE	1 participants
PMN310 175 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE Related to Study Treatment	1 participants
PMN310 175 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE Leading to Treatment Discontinuation	0 participants
PMN310 175 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE	2 participants
PMN310 350 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE Leading to Treatment Discontinuation	0 participants
PMN310 350 mg	Incidence of Treatment Emergent Adverse Events	Any Severity Grade 3 TEAE	0 participants
PMN310 350 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE Related to Study Treatment	1 participants
PMN310 350 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE	2 participants
PMN310 350 mg	Incidence of Treatment Emergent Adverse Events	Any TESAE	0 participants
PMN310 700 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE Leading to Treatment Discontinuation	0 participants
PMN310 700 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE	0 participants
PMN310 700 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE Related to Study Treatment	0 participants
PMN310 700 mg	Incidence of Treatment Emergent Adverse Events	Any Severity Grade 3 TEAE	0 participants
PMN310 700 mg	Incidence of Treatment Emergent Adverse Events	Any TESAE	0 participants
PMN310 1400 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE	3 participants
PMN310 1400 mg	Incidence of Treatment Emergent Adverse Events	Any TESAE	0 participants
PMN310 1400 mg	Incidence of Treatment Emergent Adverse Events	Any Severity Grade 3 TEAE	0 participants
PMN310 1400 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE Leading to Treatment Discontinuation	0 participants
PMN310 1400 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE Related to Study Treatment	0 participants
PMN310 2800 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE Related to Study Treatment	1 participants
PMN310 2800 mg	Incidence of Treatment Emergent Adverse Events	Any Severity Grade 3 TEAE	1 participants
PMN310 2800 mg	Incidence of Treatment Emergent Adverse Events	Any TESAE	0 participants
PMN310 2800 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE	3 participants
PMN310 2800 mg	Incidence of Treatment Emergent Adverse Events	Any TEAE Leading to Treatment Discontinuation	0 participants
Placebo	Incidence of Treatment Emergent Adverse Events	Any TEAE Related to Study Treatment	2 participants
Placebo	Incidence of Treatment Emergent Adverse Events	Any TEAE	3 participants
Placebo	Incidence of Treatment Emergent Adverse Events	Any TEAE Leading to Treatment Discontinuation	0 participants
Placebo	Incidence of Treatment Emergent Adverse Events	Any Severity Grade 3 TEAE	1 participants
Placebo	Incidence of Treatment Emergent Adverse Events	Any TESAE	0 participants

Secondary

Summary of CSF Concentrations of PMN310

Measure concentration of PMN310 in CSF

Time frame: Days 3 and 29

Arm	Measure	Group	Value (MEAN)	Dispersion
PMN310 175 mg	Summary of CSF Concentrations of PMN310	Day 3	50.05 ng/mL	Standard Deviation 21.205
PMN310 175 mg	Summary of CSF Concentrations of PMN310	Day 29	32.43 ng/mL	Standard Deviation 27.276
PMN310 350 mg	Summary of CSF Concentrations of PMN310	Day 3	78.47 ng/mL	Standard Deviation 35.281
PMN310 350 mg	Summary of CSF Concentrations of PMN310	Day 29	37.20 ng/mL	Standard Deviation 19.916
PMN310 700 mg	Summary of CSF Concentrations of PMN310	Day 3	150.10 ng/mL	Standard Deviation 50.301
PMN310 700 mg	Summary of CSF Concentrations of PMN310	Day 29	92.80 ng/mL	Standard Deviation 45.787
PMN310 1400 mg	Summary of CSF Concentrations of PMN310	Day 29	134.43 ng/mL	Standard Deviation 71.353
PMN310 1400 mg	Summary of CSF Concentrations of PMN310	Day 3	284.00 ng/mL	Standard Deviation 136.995
PMN310 2800 mg	Summary of CSF Concentrations of PMN310	Day 3	502.50 ng/mL	Standard Deviation 242.214
PMN310 2800 mg	Summary of CSF Concentrations of PMN310	Day 29	241.00 ng/mL	Standard Deviation 111.366

Secondary