ONP-002-AU-001

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.

Inclusion Criteria

Participants with suspected concussion presenting to the emergency department will be included in the study only if they satisfy all the following criteria:

1. 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.
2. Adult males and females, 18 to 55 years of age (inclusive) at screening.
3. Body mass index (BMI) ≥ 18.0 and ≤ 35.0 kg/m2, with a body weight (to 1 decimal place) ≥ 50 kg at screening.
4. 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
5. Must be able to receive 1st dose of study drug within 12 hours of injury.
6. No evidence of bleeding from the nose or visual full occlusion of the nasal cavity after a macroscopic nasal examination.
7. 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.
   • Must agree not to become pregnant or donate ova for at least 33 days after last dose of study drug.
   • Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception [Section 10.2.3]) from screening until at least 33 days after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle.
8. Male participants must:
   • Agree not to donate sperm from signing the consent form until at least 93 days after the last dose of study drug.
   • If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception (defined as use of a condom combined with use of highly effective method of contraception) from signing the consent form until at least 93 days after the last dose of study drug.
   • If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, must agree to use a condom from signing the consent form until at least 93 days after the last dose of study drug.
9. Have suitable venous access for blood sampling.
10. The patient must agree to have to give their blood without ownership to the repository for blood biomarker analysis.
11. Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.

Exclusion Criteria

Participants will be excluded from the study if they meet any of the following criteria:

1. 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.
2. Presence of penetrating brain injury.
3. 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.
4. 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.