As Incannex advances IHL-42X, a cannabinoid combination product, into phase 2/3 clinical trials for treating OSA, CEO Joel Latham praises early trial outcomes, signaling strong potential for the drug’s marketability.

Summary: Incannex Healthcare Inc provided an update on its phase 2/3 trials of IHL-42X, its drug candidate being developed for the treatment of obstructive sleep apnea (OSA), detailing preparation across 25 US sites with expansion plans into Europe. This proprietary drug, combining dronabinol and acetazolamide, aims to provide a pharmacological alternative to the commonly used PAP devices. The RePOSA trial will assess the drug’s safety and efficacy, with phase 3 to test the optimal dose over a year. Additionally, Incannex is conducting a Bioavailability/Bioequivalence study to support a New Drug Application via the FDA’s 505(b)2 pathway.

Key Takeaways:

  • Incannex is preparing for the phase 2/3 trials of IHL-42X, a drug candidate for the treatment of obstructive sleep apnea. The phase 2 trials are set to be conducted at 25 sites across the United States, with phase 3 trials planned to expand into additional sites in Europe, including Germany, Spain, Finland, and the United Kingdom.
  • IHL-42X is a fixed-dose combination drug comprising dronabinol and acetazolamide, targeted as the first pharmacological treatment option for OSA. This comes in response to the limitations of current standard care with PAP devices, which often have low patient compliance.
  • The drug’s development includes a Bioavailability/Bioequivalence study crucial for the New Drug Application intended to be submitted under the FDA’s 505(b)2 pathway. This pathway allows the company to rely on previous studies not conducted by them but by using reference listed drugs, which in this case are the components of IHL-42X—dronabinol and acetazolamide.

Clinical-stage pharmaceutical development company Incannex Healthcare Inc announced a progress update on its ongoing phase 2/3 studies for its IHL-42X drug candidate, a cannabinoid combination product in development for the treatment of obstructive sleep apnea (OSA).

IHL-42X is Incannex’s proprietary fixed-dose combination drug comprising dronabinol and acetazolamide for the treatment of OSA. The current standard of care for OSA are positive airway pressure (PAP) devices; however, patient compliance with PAP machines is limited due to patient discomfort. There are no approved drugs for OSA, and IHL-42X is designed to fill this unmet need, particularly for patients who are intolerant to PAP machines.

The RePOSA Phase 2/3 Clinical Trial

The US Food and Drug Administration (FDA) provided clearance for the multi-site phase 2/3 Investigational New Drug (IND) opening clinical trial in 2023. The trial, which has been given the name RePOSA, derived from Revealing the Efficacy of IHL-42X use in Patients with OSA, will assess the safety and efficacy of IHL-42X compared to the component active pharmaceutical ingredients, dronabinol and acetazolamide, as well as placebo.

Design of the RePOSA study consists of a phase 2 dose-ranging study that will be conducted at 25 sites in the United States. Patients in the phase 2 study will receive one of two doses of IHL-42X or placebo for four weeks. After four weeks of treatment, the patients will undergo assessment using overnight polysomnography to determine the severity of their sleep apnea, as well as various patient-reported outcomes and blood sample collection to determine the effects of IHL-42X on their sleep quality and the safety of IHL-42X.

The phase 3 component of the study will expand the trial to sites in Europe, extend the treatment period to one year, and will compare IHL-42X at the optimal dose from phase 2 to the component active pharmaceutical ingredients, dronabinol and acetazolamide, as well as placebo. The study is registered on with NCT number NCT06146101.

During the quarter, Incannex focused on preparing for patient dosing in phase 2 and achieved the following:

  • All 25 US-based phase 2 trial sites have been selected for the RePOSA study. The sites are at various stages of start-up, as follows:
  • The IHL-42X drug product has been manufactured and shipped to a depot in the US, from where it will be distributed to sites. Arrival of drug product at sites will be followed shortly by commencement of patient dosing.

Preparation for the phase 3 component of the trial is being undertaken in parallel with start-up activities for phase 2. The 25 US sites selected for the phase 2 component of the trial will also participate in phase 3. The phase 2 and phase 3 components are contained within a single protocol that has already been approved by the Institutional Review Board. The phase 3 trial will also include sites in Germany, Spain, Finland, and the United Kingdom. Progress toward phase 3 in the quarter included:

  • All 30 additional sites have been selected for phase 3. This consists of 16 sites in Germany, seven in Spain, two in Finland, and five in the United Kingdom.
  • EU-CTR package for approval to conduct the study in Europe is nearing finalization and submission.

“There are no FDA or EMA registered drugs for the treatment of sleep apnea, which we believe represents a major opportunity for Incannex to provide patients with a novel treatment option with no direct market competitors,” says president and CEO Incannex Inc, Joel Latham, in a release. 

The initial phase 2 proof-of-concept clinical trial investigating the drug candidate in patients with OSA demonstrated an average reduction in AHI of 50.7%, with 25% of subjects having a reduced AHI of >80%, according to Latham. “Importantly, we also observed a reduction in average patient oxygen desaturation index of 59.7% and markedly improved patient-reported sleep quality,” says Latham in a release. 

He adds in a release, “These results were truly remarkable and has facilitated our investment in the phase 2/3 trial. If we again observe such notable drug efficacy, safely administered over the 52 weeks of the phase 3 component of the trial, Incannex is confident that our product will be marketable.”

The IHL-42X Bioavailability/Bioequivalence Study

Incannex intends to submit a New Drug Application (NDA) for IHL-42X fixed dose combination drug to the FDA using the 505(b)2 pathway. The 505(b)2 NDA permits an applicant to rely on information on the component drug substances, via previous approved reference listed drugs, from studies not conducted by Incannex. 

The previously FDA-approved reference drugs, dronabinol and acetazolamide, correspond to the active pharmaceutical ingredients in IHL-42X. To use the FDA505(b)2 pathway, the pharmacokinetics of the active pharmaceutical ingredients in IHL-42X must compared directly to the reference listed drugs. 

The Bioavailability/Bioequivalence study is being undertaken to assess the bioavailability of IHL-42X and determine the bioequivalence to the reference listed drugs. The Bioavailability/Bioequivalence study is progressing and aims to recruit at least 116 healthy volunteers who will each receive a single dose of IHL-42X, dronabinol and acetazolamide under fasted conditions, as well as IHL-42X under fed conditions. 

After each drug is administered, patients will have blood samples collected at defined timepoints over 48 hours. These blood samples will be analysed for dronabinol, acetazolamide and their relevant metabolites. This data will be used to determine pharmacokinetic parameters for the drugs and their metabolites. Participants will also be monitored throughout the study to collect additional data on the safety of IHL-42X. 

Patient recruitment continued during the quarter; a total of 72 participants have been randomized and received a minimum of one dose in the trial. No serious adverse events have occurred to date. An additional site has been added to hasten the study and screening has commenced at the second site.

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