Safety and Tolerability of PNT001 in Patients With Acute Traumatic Brain Injury (TBI)

NCT04677829 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PNT001-002
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, multi-center, randomized, double-blind, placebo-controlled, multiple-ascending- dose trial to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of intravenous PNT001 in hospitalized patients with traumatic brain injury.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (6)

• Incidence of Treatment Emergent Adverse Events

  assess adverse events

  84 day study duration

• Incidence of Treatment Emergent Clinical Laboratory Test Abnormalities

  measure clinical laboratory values

  84 day study duration

• Incidence of Treatment Emergent Abnormalities in Physical Examination Findings

  perform physical examination

  84 day study duration

• Incidence of Treatment Emergent Abnormalities in Neurological Examination Findings

  perform neurological examination

  84 day study duration

• Incidence of Treatment Emergent Abnormalities in Vital Signs

  assess blood pressure, pulse, temperature, respiratory rate

  84 day study duration

• Incidence of Treatment Emergent Abnormalities in 12-lead Electrocardiogram Assessment

  measure ECG parameters

  84 day duration of study

Secondary Outcomes (1)

• Pharmacokinetic Properties of PNT001 in Serum

  84 day duration of study

Other Outcomes (7)

• Anti-Drug Antibodies (ADA)

  84 day duration of study

• Biomarker Measurements in Plasma

  84 day duration of study

• Effects of PNT001 on imaging parameters

  Day 3 through the remainder of the 84 day study

Study Arms (3)

PNT001 1000mg

EXPERIMENTAL

PNT001 diluted in 5% dextrose for infusion

Biological: PNT001

PNT001 4000mg

EXPERIMENTAL

PNT001 diluted in 5% dextrose for infusion

Biological: %5 dextrose for infusion

Placebo

PLACEBO COMPARATOR

5% dextrose for infusion

Biological: PNT001; Biological: %5 dextrose for infusion

Interventions

PNT001 BIOLOGICAL

30 minute infusion for PNT001 1000mg; 60 minute infusion for PNT001 4000mg

PNT001 1000mg; Placebo

%5 dextrose for infusion BIOLOGICAL

30 min placebo infusion for 1000mg; 60 minute placebo infusion for 4000mg

PNT001 4000mg; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalization due to documented evidence of TBI with Glasgow Coma Scale (GCS) Score 9-12 or GCS score of 13-15 with radiographic evidence of trauma.
• Duration from documented time of TBI event to time of start of initial dose of study drug will not exceed 24 hours.
• Signed informed consent by patient, or where applicable, patient's legally authorized representative.
• Male and females, 18- 65 years of age at time of screening (State's legal age of majority is minimum age if higher than 18).
• Female patients must meet protocol defined criteria for 1) non-childbearing potential, 2) post menopausal or 3) must have a negative pregnancy test and agree to contraception as outlined in the protocol.
• Male must agree to use acceptable contraception and refrain from sperm donation during the entire study and for 200 days after dosing has been completed.
• Has not participated in a clinical drug trial within 3 months of study start.
• Body Mass Index (BMI) of 18.5-35.0 kg/m2 and for the 4000mg dose group only, weight greater than or equal to 44.8 kg.
• Vision, hearing, speech, motor function, and comprehension sufficient for compliance with all testing procedures and assessments.

You may not qualify if:

• TBI that does not require hospitalization.
• TBI outside 24-hour window.
• GCS \< 9 within 2 hours of dosing.
• History of TBI in past 12 months that resulted in patient seeking medical attention.
• Evidence of penetrating head trauma or depressed skull fracture.
• Clinical or radiographic evidence of mass effect, midline shift, or intracranial hypertension, requiring craniotomy/craniectomy.
• Evidence of symptomatic cervical, thoracic, lumbar spine injury e.g. paresis, radiculopathy, that can be localized to the injury.
• Systemic traumatic injury that would preclude participation in study or is expected to result in long-term disability.
• Any other acute or chronic medical illness that in the judgement of the study physician results in functional impairment or impairs neuropsychiatric function.
• Any acute intoxication that in the judgement of the study physician results in significant functional impairment or impairs neuropsychiatric function.
• Any history of cancer within 5 years of enrollment with the exception of resected skin basal cell carcinoma.
• Any major surgery requiring general anesthesia 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.
• Known recent (within 6 months of study drug administration) 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.

Sponsors & Collaborators

• Pinteon Therapeutics, Inc: lead
• United States Department of Defense: collaborator

Study Sites (1)

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Larry Altstiel, MD, PhD

  Pinteon Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study drug will be administered and assessed in double-blinded fashion.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Escalating dose level cohorts; each cohort with an active and a placebo arm

Study Record Dates

• First Submitted: December 6, 2020
• First Posted: December 21, 2020
• Study Start: March 29, 2021
• Primary Completion: April 12, 2021
• Study Completion: April 12, 2021
• Last Updated: June 29, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)