Safety and Tolerability of PNT001 in Healthy Adults

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single-Ascending-Dose Trial to Evaluate the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of Intravenous PNT001 in Healthy Volunteers

This first in human study is a multi-center, randomized, double-blind, placebo-controlled single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of intravenous PNT001 in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: PNT001; Drug: Placebo

Detailed Description

This Phase 1 clinical trial is a multicenter, double-blind, single ascending dose trial evaluating safety in up to a total of 48 participants across up to 6 dose cohorts, 5 planned and 1 to be determined if an additional dose group is required. Each cohort will include 8 participants (6 active, 2 placebo) who will receive a single dose of either PNT001 or placebo. Within each cohort a sentinel group of 2 participants (1 active, 1 placebo) will be enrolled to evaluate safety and tolerability before enrolling the full cohort. If there are no safety concerns (as determined by the data and safety monitoring board [DSMB]), the remaining 6 participants (randomized as 5 active, 1 placebo) will be enrolled. This process will be followed for all additional cohorts.

After screening, and laboratory assessments at Day -1, eligible participants will be admitted to the research unit on Day 1 (or Day -1 at Investigator's discretion), where they will remain for three (or four) nights with standardized meals provided during their inpatient stay. On Day 1, participants will be randomized to receive either active drug or placebo. Study medication will be administered as a single i.v. infusion over 30 minutes (up to 60 minutes for doses greater than 2,700 mg), followed by collection of safety, tolerability, and PK data over 16 weeks. Participants will be discharged on Day 4 and will return for an outpatient study visit on Day 5 (may be phone or clinic visit), and to the study site on Days 7, 14, 28, 42, 56, 70, 84, 98, and 112.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest
  • California
    • San Diego, California, United States, 92103
      • Pacific Research Network, Inc.
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The participant provides written informed consent.
• The participant is a male or female (not of childbearing potential), 21 to 65 years of age at time of screening.
• Female participants must have documented proof that they are not of childbearing potential and must not currently be breastfeeding.
• Male participants must agree to use barrier contraceptives plus spermicide and refrain from sperm donation during the entire study and for 200 days after dosing has been completed.
• The participant must not have participated in a clinical drug trial within 3 months of study start, or within 5 half-lives, unless the study blind has been broken and the participant was known to be on placebo
• The participant must have a body mass index of 18.5 to 30 kg/m^2

Exclusion Criteria:

• Any contraindication or inability to undergo lumbar puncture due to anticoagulant use, platelet level, or coagulation study/INR result
• 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
• A history of smoking or using tobacco products within 3 months before study drug administration
• A history of drug or alcohol abuse as defined in 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
• A history or current status of schizophrenia, schizoaffective disorder or bipolar disorder, untreated major depression (DSM-V or ICD-10 criteria)
• Any significant illness or infection requiring intervention within the prior 30 days as determined by the investigator and sponsor
• An indication of potential suicidality risk based on the C-SSRS assessment
• Any of the following abnormalities:
• serum creatinine > 1.5 mg/dL at screening
• AST or ALT > 2x the upper limit of normal at screening
• blood pressure > 140/90 Hg at screening or baseline
• QTcF > 470 msec at screening or baseline
• A known hypersensitivity to any components of the PNT001 drug product or placebo (5% dextrose)
• Current use of or plan to use any medication (prescription or over-the-counter) that would potentially affect the assessment of the pharmacokinetics, pharmacodynamics, or immunogenicity of PNT001

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PNT001; Single escalating doses of intravenous PNT001 administered as a 30 minute infusion at doses of 33mg, 100mg, 300mg, 900mg, 2700mg, and as a 60 minute infusion at 4000 mg	Biological: PNT001; PNT001 diluted in 5% dextrose
PLACEBO_COMPARATOR: Placebo; Single intravenous dose of vehicle administered as a 30 minute infusion up to 2700 mg and as a 60 minute infusion at 4000 mg	Drug: Placebo; 5% dextrose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events	assess adverse events during 16 week duration of study	16 weeks
Incidence of Treatment Emergent Clinical Laboratory Test Abnormalities	measure clinical laboratory values during 16 week duration of study	16 weeks
Incidence of Treatment Emergent Abnormalities in Physical Examination Findings	observe skin, eyes, ears, nose, throat, cardiac and pulmonary status, abdomen, and extremities for any abnormalities	16 weeks
Incidence of Treatment Emergent Abnormalities in Neurological Examination Findings	perform a neurological assessment of orientation, cranial nerve function, limb function for presence of involuntary movements, muscle mass, tone, and strength, coordination, reflexes, sensation, joint position, gait, Romberg test	16 weeks
Incidence of Treatment Emergent Abnormalities in Blood Pressure	measure resting pulse rate as beats per minute	16 weeks
Incidence of Treatment Emergent Abnormalities in Pulse Rate	measure systolic and diastolic blood pressure in mmHg	16 weeks
Incidence of Treatment Emergent Abnormalities in 12 lead Electrocardiogram Assessment	measure QT and calculate QTcF value	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic properties of PNT001 in Serum	measure concentration of PNT001 in serum	16 weeks
Pharmacokinetic properties of PNT001 in Cerebrospinal Fluid (CSF)	measure concentration of PNT001 in CSF	28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - total tau	measure CSF concentrations of total tau	28 days
Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - cis-pT231 tau	measure CSF concentrations of cis-pT231 tau	28 days
Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - total pT231 tau	measure CSF concentrations of total pT231 tau	28 days
Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - NfL	measure CSF concentrations of Neurofilament Light Chain (NfL)	28 days
Pharmacodynamic effects of PNT001 in Serum - NfL	measure serum concentrations of Neurofilament Light Chain (NfL)	28 days
Immunogenicity of PNT001 - ADA	measure presence of antidrug antibodies (ADA) in serum	16 weeks

Collaborators and Investigators

• Sponsor: Pinteon Therapeutics, Inc
• Investigators: Study Director: Larry D. Altstiel, MD, PhD, Pinteon Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 17, 2019
• Primary Completion (ACTUAL): February 15, 2021
• Study Completion (ACTUAL): February 15, 2021

Study Registration Dates

• First Submitted: September 17, 2019
• First Submitted That Met QC Criteria: September 18, 2019
• First Posted (ACTUAL): September 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 19, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: PNT001-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No