Results from a Phase-1 clinical trial of Incannex’s anti-inflammatory drug IHL-675A in healthy volunteers adds to the company’s confidence in proceeding with assessment in patients with inflammatory diseases.

Medicinal cannabis and psychedelic therapies company, Incannex Healthcare (ASX:IHL) has announced promising final results from the Phase-1 clinical trial undertaken to assess pharmacokinetics and safety of the anti-inflammatory drug IHL-675A.

IHL-675A is a combination cannabinoid drug comprising cannabidiol (CBD) and hydroxychloroquine (HCQ) in a fixed dose combination.

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 the company’s international patent application over the drug.

The Phase-1 trial measured the safety, tolerability, and pharmacokinetic profiles of IHL-675A compared to reference listed drugs, Epidiolex (CBD) and Plaquenil (HCQ).

Three cohorts of 12 participants – 36 in total – received either IHL-675A, CBD or HCQ and the clinical assessments were identical across the three arms of the trial.

Participants were monitored for adverse events and had blood samples collected for
pharmacokinetic (PK) analysis over a four-week period.

PK analysis determines the absorption, distribution, metabolism, and excretion (also known as ADME) of drugs in the body.

The trial was conducted by CMAX Clinical Research in Adelaide and managed by Avance Clinical.

Safety and tolerability results

IHL-675A was well tolerated, with no adverse events of concern and no serious adverse events reported.

The same number of treatment-related Treatment Emergent Adverse Events (TEAEs) were reported for IHL-675A as for Epidiolex.

TEAEs included abdominal pain, dizziness, fatigue, frequent bowel movements, headache, and somnolence.

All TEAEs were minor except one incidence of moderate severity abdominal cramps which resolved soon after onset.

Both active pharmaceutical ingredients, CBD and HCQ, are absorbed from IHL-675A.

Trends in PK profiles indicate that the uptake of CBD may be more rapid for IHL-675A than Epidiolex and uptake of HCQ may be slower for IHL-675A than Plaquenil.

This could be advantageous for IHL-675A. CBD provides immediate relief for inflammation and pain whereas HCQ is a slower acting molecule and provides extended relief.

Crucial step to move forward

The safety and pharmacokinetic data from the Phase-1 clinical trial in healthy volunteers adds to the company’s confidence in proceeding with assessment of IHL-675A in patients with inflammatory diseases.

IHL chief scientific officer Dr Mark Bleackley said results from the Phase-1 trial are a critical milestone in the development of IHL-675A.

“Data on the safety and pharmacokinetics of the drug combination are essential for supporting to administration of the drug to rheumatoid arthritis patients on a daily basis over an extended period in the Phase-2 trial,” he said.

“We are excited to better understand the therapeutic potential of IHL-675A as the development pipeline continues to progress.”

Next Steps – Phase-2 Trial in rheumatoid arthritis patients

IHL said as HCQ is already approved for treatment of rheumatoid arthritis, it is the first indication for which IHL-675A will be assessed in a Phase-2 clinical trial.

The trial will include 120 participants who meet the eligibility criteria, and participants will be randomised to one of four arms – either IHL-675A, CBD alone, HCQ alone or placebo.

The primary endpoint for the study is pain and function relative to baseline
determined via the score on the RAPID3 assessment at 24 weeks. 

Plans for Phase-2 trial in other inflammatory diseases

Trial designs for Phase-2 studies in patients with inflammatory bowel disease and lung inflammation are also being developed.

The treatment of these three indications has a combined global annual market
size of exceeding US$125 billion annually.

IHL has filed a request for pre-IND meeting on the development of IHL-675A for treatment of arthritis with the US Food and Drug Administration (FDA).

Following the pre-IND meeting, IHL intends to open an IND in parallel with the Australian Phase-2 study.

This will enable trials in the US if the Australian study continues to support the therapeutic potential of IHL-675A in patients with arthritis.

Positive in-vivo results

In March of 2021, IHL announced results from an in vivo model of rheumatoid arthritis where IHL-675A was observed to benefit the treatment of rheumatoid arthritis in mice greater than that of CBD or HCQ alone.

HCQ, is widely used for treatment of rheumatoid arthritis in the form of hydroxychloroquine sulphate, marketed as Plaquenil.

An improvement to patient wellbeing achieved by IHL-675A would potentially open a major economic opportunity for IHL arthritis.

IHL CEO and managing director Joel Latham said a large sub-group of people with rheumatoid arthritis are using hydroxychloroquine or cannabidiol to help to alleviate their symptoms.

“We are delighted with the safety data and with the unique pharmacokinetic characteristics of IHL-675A that may be beneficial for patients with rheumatoid arthritis,” he said.

“By undertaking pivotal clinical studies over IHL-675A, we intend to disrupt the markets for both CBD and hydroxychloroquine as they currently pertain to the treatment of rheumatoid arthritis.”

This article was developed in collaboration with Incannex Healthcare, a Stockhead advertiser at the time of publishing.

This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.