Incannex Healthcare Ltd (ASX:IHL, NASDAQ:IXHL) has received ethics approval from the Bellberry Human Research Ethics Committee (HREC) to start the phase 1 clinical trial investigating safety, tolerability and pharmacokinetics (uptake and metabolism) of combination cannabinoid (CBD), anti-inflammatory drug IHL-675A.
The clinical-stage pharmaceutical company is developing medicinal cannabinoid pharmaceutical products and psychedelic medicine therapies for unmet medical needs.
IHL-675A comprises a combination of cannabidiol (CBD) and hydroxychloroquine (HCQ). HCQ is a disease-modifying anti-rheumatic drug that regulates the activity of the immune system, which may be overactive in some conditions. HCQ can modify the underlying disease process, rather than simply treating the symptoms.
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This news has seen the company's securities rise as much as 11.9% to A$0.235 intra-day.
Ethics approval gives IHL the green light to test its proprietary multi-use, anti-inflammatory drug, which is a combination cannabinoid drug comprising CBD and HCQ in a fixed dose combination.
The trial will be performed at CMAX Clinical Research, a dedicated and experienced clinical trial centre in Australia, and managed by Avance Clinical and will apply to regulatory submissions for all three IHL-675A development programs: rheumatoid arthritis, inflammatory bowel disease and lung inflammation.
IHL-675A was observed to outperform either CBD and HCQ in various pre-clinical models of inflammation, including in vivo models of rheumatoid arthritis, inflammatory bowel disease and lung inflammation.
Synergistic anti-inflammatory activity of CBD and HCQ was observed in these distinct pre-clinical studies and was evidence to support IHL’s international patent application over the drug.
Significant milestone
CEO and managing director Joel Latham said of the ethics approval: “Approval to begin our Australian phase 1 trial is a significant milestone for Incannex and clinicians treating patients with disorders for which inflammation is the underlying cause.
"There’s a growing trend whereby patients are using CBD to treat, or supplement their existing treatments, for inflammation disorders.
"We have observed in established models of inflammation that IHL-675A is a stronger anti-inflammatory cannabinoid-based drug than CBD administered alone, hence we are delighted and excited to take IHL-675A to the clinic for the first time.”
Trial measurements will be done in comparison with reference-listed drugs, Epidiolex (CBD) and Plaquenil (HCQ).
Three cohorts of 12 participants (36 in total) will receive either IHL-675A, CBD or HCQ and the assessments will be identical across the three arms of the trial.
Incannex Healthcare chief scientific officer Dr Mark Bleackley said: “The aims of the trial are to demonstrate that there are no, or minimal, additional side effects associated with the combination of CBD and HCQ compared to each drug alone and that the uptake and metabolism, otherwise known as pharmacokinetics, of the two drugs do not materially interfere with one another.”
Three FDA IND applications
If the company sees clinical success, the results of the phase 1 clinical trial will form part of three US Food and Drug Administration (FDA) investigational new drug (IND) applications for each of the initial three indications IHL is targeting for IHL-675A.
The markets for rheumatoid arthritis, inflammatory bowel disease and lung inflammation, represent major targets for Incannex to pursue with IHL-675A. The treatment of these indications has a combined global annual market size of exceeding US$125 billion per annum.
Once the IND applications are evaluated and approved, IHL will look to conduct clinical trials partly or wholly in the United States.
Patient recruitment is anticipated to commence in August 2022.
More clinical trials completed
Incannex has also finished the formulation development of IHL-675A and the first batch of product has been manufactured.
The formulation development process included multiple experiments conducted to determine the ideal excipients to use in formulation of IHL-675A.
Other assessments included the characterisation of the dissolution of both active pharmaceutical ingredients (CBD and HCQ) from the IHL-675A gel capsule and ensuring that the dissolution profile was consistent with the reference listed drugs.
Data from the characterisation of the IHL-675A gel capsules, the quality assessment and early timepoints in the stability analysis were critical components of the HREC submission package.
These results and data from ongoing stability studies will be necessary for future regulatory submissions, including IND and new drug applications with the FDA and corresponding applications with other regulatory agencies.
Stability studies to establish the shelf life of the IHL-675A gel capsule product are also underway.
Notably, the company’s formulation partner’s manufacturing facilities have been inspected and approved for good manufacturing practices (GMP) by several regulatory agencies including FDA, TGA, Health Canada and MHRA.
Production of IHL-675A soft gel capsules can quickly ramp up to commercial quantities when required.
About IHL’s studies
Incannex has demonstrated that IHL-675A components, CBD and HCQ, act synergistically to inhibit production of key inflammatory cytokines in an in vitro study of human cells and in four distinct successful in vivo experiments using established models of inflammation.
Incannex has evaluated the results of these experiments and believes IHL-675A to be a multi-use drug candidate suitable for the prevention and treatment of inflammation, with an initial focus on inflammatory lung conditions (acute respiratory distress syndrome, COPD, asthma and bronchitis), rheumatoid arthritis and inflammatory bowel disease.
IHL has completed a pre-IND meeting with the FDA to discuss the regulatory pathway for the development of IHL-675A in the United States and plans to open INDs for each of the three indications.
FDA agreed that marketing applications for IHL-675A should be 505(b)(2) applications due to the existence of certain safety and efficacy information on the active ingredients of IHL-675A originating from historical studies that we are entitled to use in a new drug application.