Oragenics, Inc.
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.
Mild Traumatic Brain Injury, Concussion
Neurosteroid enantiomer
PHASE2
Up to 40 participants will be randomized 1:1 to receive either ONP-002 or placebo, using a block randomization algorithm. * Control Arm: Placebo * Interventional Arm: 8 mg BID ONP-002 (a demethylated analogue of the enantiomer of progesterone) Intranasal Participants will receive BID doses of 8 mg ONP-002 or placebo for 5 consecutive days with a total of up to 9 doses, through IN administration. If participants receive their first dose on the morning of Day1, they will receive a total of 9 doses. If participants receive their first dose on the evening of Day 1, they will receive a total of 8 doses. The last dose of study drug for all participants will be administered in the morning on Day 5. Objectives Endpoints To determine the feasibility of administering ONP-002 in acute mTBI patients within 12 hours of injury. • Time to enrolment post injury and first treatment with ONP-002 To investigate the safety and tolerability of multiple IN doses of ONP-002 in patients with mTBI. • Incidence and severity of AEs * Changes in vital sign measurements * Changes in clinical laboratory results * Changes in ECG parameters * Change from baseline in macroscopic nasal examination findings To measure levels of ONP-002 in plasma following multiple IN doses in patients with mTBI. • Plasma concentrations of ONP-002 * Accumulation ratio (RAUC, and RCmax) To establish POC that IN ONP-002 administration within 12 hours of injury results in blood biomarker/functional changes consistent with the proposed mechanism of action. • Changes in blood biomarker and functional scores (clinical improvement over time) from baseline in ONP-002 treated participants compared to placebo. To establish a reproducible protocol for the combination of IN ONP-002 dosing and blood biomarker draws in mTBI patients for up to 5-days post-injury by; * Establishing if blood biomarkers can be used as a surrogate efficacy endpoint for mTBI that could be used in later phase studies. • Correlation between blood biomarkers and patient reported outcomes, cognitive performance, and visual motor performance * Assess correlation of the below scores with initial positive blood biomarker findings prior to first dose: * Post-traumatic amnesia (PTA) * Brief loss or alteration of consciousness (LOC and AOC) * Standardised Assessment of Concussion (SAC) scores Screening * Medical history * Prior medication use * Height and weight * Demographics (including age, race, sex, and ethnicity) * Pregnancy test * Computed Tomography (CT) Scan * Blood Glial fibrillary acidic protein (GFAP) * GCS * Neurological assessment checklist (LOC, PTA, AOC) * Neurological assessment signs and symptoms checklist Safety and Tolerability * Concomitant medication use * Physical examination * Adverse event monitoring * Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, respiration rate) * 12-lead electrocardiogram (ECG) * Clinical laboratory safety assessments (haematology, serum chemistry, coagulation and endocrinology) * Macroscopic nasal examination Pharmacodynamics Blood samples will be collected throughout the study for analysis of ONP-002 levels, and mTBI biomarkers including (but not limited to): * GFAP * Neurogranin * ST2 (soluble interleukin 1 receptor-like 1) Efficacy Efficacy endpoints will include the following assessment of patient reported symptom severity and clinical assessments of cognitive and visual-motor integrity: * Rivermead Post-Concussion Questionnaire (RPQ) * 5-minute DANA neurocognitive battery * King-Devick (K-D) 3-minute visual motor test * 10 and 30-day functional status evaluation using the Glasgow Outcome Scale - Extended (GOS-E) Safety and Tolerability The number of treatment-emergent AEs (TEAEs) as well as the number and percentage of participants with at least one TEAE, will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) system organ class and preferred term and tabulated for each dose group. Summaries of TEAEs by severity and relationship will also be presented. Summaries will also be presented for TEAEs leading to death, serious TEAEs and for TEAEs leading to study withdrawal. Observed values and changes from baseline in vital signs (including oxygen saturation levels), macroscopic nasal examination, pulmonary function, ECG parameters and continuous clinical laboratory parameters will be summarized at each scheduled timepoint by dose group using descriptive statistics (n, mean, standard deviation, minimum, maximum, median). Categorical clinical laboratory data will be summarized at each scheduled timepoint using participant counts and percentages and tabulated by dose group. Abnormalities in clinical laboratory parameters and ECG parameters QTcF will be tabulated by dose group showing participant counts and percentages. Physical examination findings will be listed only. Pharmacodynamics Individual participant blood biomarker concentrations at each timepoint will be listed and summarized by treatment using descriptive statistics (n, mean, standard deviation, coefficient of variation, minimum, maximum, median, and geometric mean) for each dose group. Efficacy Observed values and changes from baseline of efficacy measures (RPQ, DANA 5-minute neurocognition test, K-D 3-minute visual motor test, GOS-E) will be summarized at each scheduled timepoint by treatment arm using descriptive statistics (n, mean, standard deviation, minimum, maximum, median). Participants will be screened for study eligibility in the hospital Emergency Department on Day 1. Eligible participants will be transferred and confined at the clinical site until completion of post first dose assessments on Day 1 after which they will be discharged. Participants will receive a daily telephone call (reminder to administer) from clinic staff on days when they are required to self-administer at home and to complete their study diary. Study participants will then be required to attend the clinical research facility for further study assessments on Days 2, 5 and 10, and an end of study assessment on Day 30. Home nursing study assessments may be provided for participants unable to attend the clinical research facility for scheduled visits. If participants experience any clinically significant adverse events (AEs) they may remain at the study site for further observation at the discretion of the Principal Investigator (PI). The expected total maximum study duration for participants will be 30 days, which includes a screening on Day 1, a 5-day treatment period, and a 25-day follow-up period. ONP-002 is being developed for the treatment of mTBI (concussion). A Phase 1 healthy adults study exploring the safety and tolerability of single and multiple ascending IN doses of ONP-002 has been completed. The current phase IIa study aims to establish that ONP-002 is safe and feasible for acute (first dose administered within 12 hours of injury) IN administration in patients with mTBI while establishing protocols for administration and proof of concept (POC) using blood biomarker panels, cognitive and visual motor assessments to be used in later phase studies.
| Study Type : | INTERVENTIONAL |
| Estimated Enrollment : | 40 participants |
| Masking : | QUADRUPLE |
| Masking Description : | Randomized and blinded parallel study with a placebo and treatment arm at a ratio of 1:1 |
| Primary Purpose : | TREATMENT |
| Official Title : | 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 |
| Actual Study Start Date : | 2025-06-01 |
| Estimated Primary Completion Date : | 2026-01-01 |
| Estimated Study Completion Date : | 2026-03-31 |
Information not available for Arms and Intervention/treatment
| Ages Eligible for Study: | 18 Months to 60 Months |
| Sexes Eligible for Study: | ALL |
| Accepts Healthy Volunteers: |
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Alfred Hospital
Melbourne, Victoria, Australia, 3181