A Randomised, Double-blind, Placebo-controlled Phase 2a Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ONP-002 in Adults With Mild Traumatic Brain Injury

NCT06870240 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: ONP-002-AU-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase IIa, randomized, double-blind, placebo-controlled pilot study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ONP-002 in adults with mild traumatic brain injury (mTBI). Broadly, a mTBI, often referred to as a concussion, is a type of head trauma that causes temporary disruption to brain function, usually resulting from a blow to the head, fall, or sudden movement, and is often characterised by symptoms of headache, dizziness, confusion, memory problems, and difficulty concentrating, without significant loss of consciousness or structural brain damage on imaging tests. The study will enroll up to 40 participants into 2 parallel treatment arms, of 20 patients each, who will receive either 16 mg (8 mg twice daily \[BID\]) intranasal (IN) ONP-002 or placebo, at 8-12-hour intervals consecutively for 5 days with a total of up to 9 doses.

Conditions

Mild Traumatic Brain Injury, Concussion

Keywords

concussion, traumatic brain injury, biomarkers, cognition, visual-motor

Outcome Measures

Primary Outcomes (1)

• Patient symptom reporting

  Neurological questionnaires for patient symptoms including Rivermead

  Days 2, 5, 10 and 30 post-injurt

Study Arms (2)

92mg of Hydroxy-propyl beta-cyclodextrin as a spray-dried powder

PLACEBO COMPARATOR

The placebo is 92mg of Hydroxy-propyl beta-cyclodextrin as a spray-dried powder

Drug: Neurosteroid enantiomer

ONP-002 treatment

ACTIVE COMPARATOR

ONP-002 is 8mg API and 92 Hydroxy-propyl beta-cyclodextrin as a spray-dried powder

Drug: Neurosteroid enantiomer

Interventions

Neurosteroid enantiomer DRUG

A non-natural synthetic neurosteroid enantiomer considered a new chemical entity

92mg of Hydroxy-propyl beta-cyclodextrin as a spray-dried powder; ONP-002 treatment

Eligibility Criteria

• Age: 18 Months - 60 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants with suspected concussion presenting to the emergency department will be included in the study only if they satisfy all the following criteria:
• Participant or legal representative is willing and capable of giving written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
• Adult males and females, 18 to 55 years of age (inclusive) at screening.
• Body mass index (BMI) ≥ 18.0 and ≤ 35.0 kg/m2, with a body weight (to 1 decimal place) ≥ 50 kg at screening.
• Must be diagnosed with a mTBI by all the following measures:
• Negative CT scan for acute traumatic lesions
• Elevated Blood Glial fibrillary acidic protein (GFAP) (≥22 pg/mL)
• Glasgow Coma Scale (GCS) score \>12
• Neurological Signs and Symptoms Checklist with history of loss/altered consciousness
• Neurological PTA, LOC and AOC checklist
• Must be able to receive 1st dose of study drug within 12 hours of injury.
• No evidence of bleeding from the nose or visual full occlusion of the nasal cavity after a macroscopic nasal examination.
• Female patients if of childbearing potential (defined as any female who has experienced menarche and who has not undergone surgical sterilisation and is not postmenopausal):
• Must be known to not be pregnant based on a urine or blood test prior to first dose administration.
• Must not be breastfeeding, lactating or planning pregnancy during the study period.

You may not qualify if:

• Participants will be excluded from the study if they meet any of the following criteria:
• History or presence of other significant disorder that at the discretion of the PI or delegate is considered "serious" classifying the participant as "not a good candidate" for the study.
• Presence of penetrating brain injury.
• Treatment with an investigational drug in another clinical trial within 60 days or 5 half-lives of the other investigational drug (whichever is longer) prior to the first administration of study drug in this trial.
• Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
• Screen Failures Participants who consent to participate in the study but fail to meet the eligibility criteria at any point during the Screening Period and until randomisation are defined as screening failures. The reason for each screening failure will be recorded on the appropriate screening and enrolment log.
• Re-Screening Participants who fail screening are not permitted to be re-screened. 7.5 Participant Withdrawal Criteria
• Participants will be advised that they are free to withdraw from the study at any time for any reason or, if necessary, the PI (or delegate) may discontinue a participant from the study to protect the participant's wellbeing. A participant may voluntarily withdraw or be withdrawn from the study for reasons including, but not limited to, the following:
• The need to take medication which may interfere with study measurements;
• Intolerable/unacceptable AEs;
• Noncompliance of the participant with the protocol;
• Pregnancy, as indicated in Section 12.7;
• Withdrawal of consent; or
• If, in the PI's (or delegate's) judgement, it is in the participant's best interest.
• The Sponsor will be notified as soon as possible of any participant withdrawals. The date and reasons for withdrawal will be recorded in the eCRF.

Sponsors & Collaborators

• Oragenics, Inc.: lead

Study Sites (1)

Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

MeSH Terms

Conditions

Brain Concussion; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomized and blinded parallel study with a placebo and treatment arm at a ratio of 1:1
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: ONP-002, is a novel neurosteroid shown to reduce inflammation in the brain. The drug is a non-natural synthetic enantiomer given as an intranasal powder to increase availability of the therapeutic to the brain after traumatic brain injury.

Study Record Dates

• First Submitted: March 5, 2025
• First Posted: March 11, 2025
• Study Start: June 1, 2025
• Primary Completion: January 1, 2026
• Study Completion: March 31, 2026
• Last Updated: March 11, 2025

Record last verified: 2025-03

Locations

AU (1)