Review Board Approves Phase 2/3 Trial of IHL-42X in Obstructive Sleep Apnea

Author(s):

In a phase 2 proof-of-concept study, IHL-42X, a drug for obstructive sleep apnea, more significantly reduced apnea-hypopnea index and oxygen desaturation index than placebo.

According to a recent announcement, an independent Institutional Review Board (IRB) has approved the protocol for Incannex’s phase 2/3 RePOSA trial (NCT06146101) assessing its investigational agent IHL-42X in patients with obstructive sleep apnea (OSA). Start-up for the trial is currently in progress with 24 sites selected in the US, 13 in Germany, 4 in Spain, and 2 in Finland.¹

IHL-42X is a proprietary synergistic composition drug comprising low-dose dronabinol, a synthetic form of tetrahydrocannabinol, and acetazolamide, a carbonic anhydrase inhibitor. The goal of RePOSA, a randomized, double-blind trial, is to assess the safety and efficacy of IHL-42X in patients with OSA who are intolerant, non-compliant, or naïve to positive airway pressure. At least 560 patients will be recruited, with a total of 355 patients receiving the study drug over the course of the trial.

RePOSA consists of 2 component studies. The phase 2 study will be a 4-week dose-finding study comparing 2 dose strengths of IHL-42X (low dose: 2.5 mg dronabinol, 125 mg acetazolamide; high dose: 5 mg dronabinol, 250 mg acetazolamide) to placebo. Efficacy and safety results of this stage will be used to select the dose strength of IHL-24X and corresponding doses of dronabinol and acetazolamide in the phase 3 portion of the trial.

The phase 3 study, a 52-week trial, will compare the optimal dose strength identified in phase 2 to the component active pharmaceutical ingredients, dronabinol and acetazolamide, at equivalent dose strengths, as well as placebo. The 4 treatment groups are: IHL-42X (optimal dose from phase 2), acetazolamide (equivalent dose strength to that in the IHL-42X optimal dose strength), dronabinol (equivalent dose strength to that in the IHL-42X optimal dose strength) and placebo. The treatment groups will enroll approximately 165 patients in IHL-42X, 55 patients in dronabinol, 55 in acetazolamide, and 165 in placebo, for a total of approximately 440 patients.

Change in apnea-hypopnea index (AHI), the primary end point, is the same throughout both the phase 2 and 3 portions of the program. In terms of trial inclusion, patients must have an AHI of at least 15 and agree to not take any form of cannabis or cannabinoid while participating. In addition, female patients of childbearing potential must agree to use 2 approved methods of contraception and males must agree to use at least 1 approved method of contraception while engaging in sexual activity from study day 1.

The RePOSA study follows a phase 2 proof-of-concept study in which IHL-42X reduced the primary end point of AHI relative to baseline in all 3 doses assessed. The results, announced in June 2022, showed that low dose IHL-42X reduced AHI by at least 50% relative to baseline in 62.5% of individuals and by at least 80% in 25% of participants on the drug. In addition, the low dose group reduced AHI to a greater extent than predicted based on published data for dronabinol and acetazolamide alone.

The proof-of-concept study also studied the effect of IHL-42X on oxygen desaturation index (ODI), a key component of the pathology of OSA and contributor to daytime sleepiness. On night 7 of the treatment period, all 3 doses of IHL-42X reduced ODI to a greater extent than placebo. For low and medium dose IHL-42X, the difference in reduction in ODI relative to baseline compared with placebo was statistically significant (P <.05). Furthermore, patients on the study drug more frequently reported that their sleep quality was good or very good than placebo, with the highest level of patient-reported sleep quality observed with low and high dose IHL-42X.²

REFERENCES
1. Incannex recieves IRB approval for the RePOSA Phase 2/3 clinical trial protocol to assess IHL-42X drug in patients with obstructive sleep apnea. News release. Incannex. January 17, 2024. Accessed January 18, 2024. https://finance.yahoo.com/news/incannex-receives-irb-approval-reposa-123000790.html
2. Incannex announces positive results from phase 2 clinical trial investigating the effect of IHL-42X for treatment of obstructive sleep apnea. Incannex. June 3, 2022. Accessed January 18, 2024. https://www.prnewswire.com/news-releases/incannex-announces-positive-results-from-phase-2-clinical-trial-investigating-the-effect-of-ihl-42x-for-treatment-of-obstructive-sleep-apnoea-301560782.html