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Safety and Tolerability of PNT001 in Healthy Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04096287
Recruitment Status : Completed
First Posted : September 19, 2019
Last Update Posted : February 23, 2021
Sponsor:
Information provided by (Responsible Party):
Pinteon Therapeutics, Inc

Tracking Information
First Submitted Date  ICMJE September 17, 2019
First Posted Date  ICMJE September 19, 2019
Last Update Posted Date February 23, 2021
Actual Study Start Date  ICMJE September 17, 2019
Actual Primary Completion Date February 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2019)
  • Incidence of Treatment Emergent Adverse Events [ Time Frame: 16 weeks ]
    assess adverse events during 16 week duration of study
  • Incidence of Treatment Emergent Clinical Laboratory Test Abnormalities [ Time Frame: 16 weeks ]
    measure clinical laboratory values during 16 week duration of study
  • Incidence of Treatment Emergent Abnormalities in Physical Examination Findings [ Time Frame: 16 weeks ]
    observe skin, eyes, ears, nose, throat, cardiac and pulmonary status, abdomen, and extremities for any abnormalities
  • Incidence of Treatment Emergent Abnormalities in Neurological Examination Findings [ Time Frame: 16 weeks ]
    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
  • Incidence of Treatment Emergent Abnormalities in Blood Pressure [ Time Frame: 16 weeks ]
    measure resting pulse rate as beats per minute
  • Incidence of Treatment Emergent Abnormalities in Pulse Rate [ Time Frame: 16 weeks ]
    measure systolic and diastolic blood pressure in mmHg
  • Incidence of Treatment Emergent Abnormalities in 12 lead Electrocardiogram Assessment [ Time Frame: 16 weeks ]
    measure QT and calculate QTcF value
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2019)
  • Pharmacokinetic properties of PNT001 in Serum [ Time Frame: 16 weeks ]
    measure concentration of PNT001 in serum
  • Pharmacokinetic properties of PNT001 in Cerebrospinal Fluid (CSF) [ Time Frame: 28 days ]
    measure concentration of PNT001 in CSF
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2019)
  • Pharmacokinetic properties of PNT001 in Plasma [ Time Frame: 16 weeks ]
    measure concentration of PNT001 in plasma
  • Pharmacokinetic properties of PNT001 in Cerebrospinal Fluid (CSF) [ Time Frame: 28 days ]
    measure concentration of PNT001 in CSF
Current Other Pre-specified Outcome Measures
 (submitted: December 2, 2019)
  • Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - total tau [ Time Frame: 28 days ]
    measure CSF concentrations of total tau
  • Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - cis-pT231 tau [ Time Frame: 28 days ]
    measure CSF concentrations of cis-pT231 tau
  • Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - total pT231 tau [ Time Frame: 28 days ]
    measure CSF concentrations of total pT231 tau
  • Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - NfL [ Time Frame: 28 days ]
    measure CSF concentrations of Neurofilament Light Chain (NfL)
  • Pharmacodynamic effects of PNT001 in Serum - NfL [ Time Frame: 28 days ]
    measure serum concentrations of Neurofilament Light Chain (NfL)
  • Immunogenicity of PNT001 - ADA [ Time Frame: 16 weeks ]
    measure presence of antidrug antibodies (ADA) in serum
Original Other Pre-specified Outcome Measures
 (submitted: September 18, 2019)
  • Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - total tau [ Time Frame: 28 days ]
    measure CSF concentrations of total tau
  • Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - cis-pT231 tau [ Time Frame: 28 days ]
    measure CSF concentrations of cis-pT231 tau
  • Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - total pT231 tau [ Time Frame: 28 days ]
    measure CSF concentrations of total pT231 tau
  • Pharmacodynamic effects of PNT001 in Cerebrospinal Fluid - NfL [ Time Frame: 28 days ]
    measure CSF concentrations of Neurofilament Light Chain (NfL)
  • Pharmacodynamic effects of PNT001 in Serum - NfL [ Time Frame: 28 days ]
    measure serum concentrations of Neurofilament Light Chain (NfL)
  • Immunogenicity of PNT001 - ADA [ Time Frame: 16 weeks ]
    measure presence of antidrug antibodies (ADA) in blood
 
Descriptive Information
Brief Title  ICMJE Safety and Tolerability of PNT001 in Healthy Adults
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • Biological: PNT001
    PNT001 diluted in 5% dextrose
  • Drug: Placebo
    5% dextrose
Study Arms  ICMJE
  • 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
    Intervention: Biological: PNT001
  • 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
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 19, 2021)
49
Original Estimated Enrollment  ICMJE
 (submitted: September 18, 2019)
48
Actual Study Completion Date  ICMJE February 15, 2021
Actual Primary Completion Date February 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04096287
Other Study ID Numbers  ICMJE PNT001-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Pinteon Therapeutics, Inc
Study Sponsor  ICMJE Pinteon Therapeutics, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Larry D. Altstiel, MD, PhD Pinteon Therapeutics, Inc
PRS Account Pinteon Therapeutics, Inc
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP