Incannex’ Phase-2 trial can potentially open the door to a US$125 billion market for the treatment of rheumatoid arthritis, inflammatory lung conditions, and inflammatory bowel disease.

Following a successful Phase-1 trial, medical cannabis company Incannex Healthcare (ASX:IHL) has now commenced the much anticipated Phase-2 clinical trial of proprietary drug IHL-675A in patients with rheumatoid arthritis (RA).

The Phase-2 trial will assess the efficacy, safety and tolerability of IHL-675A compared to the drug’s component ingredients, namely cannabidiol (CBD) and hydroxychloroquine (HCQ), and placebo.

The treatments will involve 120 patients over a 24-week period and are double blinded, meaning neither the investigators nor patients will know which treatment an individual is receiving.

The trial will be managed by Avance Clinical, the largest full-service Australian and US clinical research organisation (CRO), which has previously delivered clinical trials in Australia, New Zealand and the US.

For this trial, Avance is expected to identify and onboard 8-10 clinical trial sites with expertise in RA, and conduct patient recruitment and assessments.

Avance will also manage the sites and study conduct, ensure that the data is of necessary quality for submission to regulatory agencies, such as the US FDA.

“This trial is a key milestone in the IHL-675A development program,” said Incannex Chief Scientific Officer, Dr Mark Bleackley.

“We are excited to continue the development of this drug product to determine whether the remarkable preclinical efficacy we observed for IHL-675A in an animal disease model for arthritis is also seen to a similar extent in humans.”

Encouraging preclinical results

Prior to commencing the Phase-1 trial, Incannex observed positive results for IHL-675A from an animal model of RA.

In these preclinical trials, IHL-675A was observed to be more effective than a standard dose of HCQ (hydroxychloroquine) at reducing arthritis across multiple assessments.

These assessments concluded that the reduction in disease measures achieved by IHL-675A was 1.06 times to 3.52 times higher than HCQ alone at the standard dose.

These promising observations led the company to prioritise a Phase-1 clinical trial of IHL-675A, particularly given that HCQ (marketed as Plaquenil) has been used as a common long-standing treatment prescribed for RA.

In the subsequent Phase-1 clinical trial in humans, IHL-675A was observed to be well tolerated, with no adverse events of concern.

What to expect in Phase-2 trial

The current Phase-2 trial will now recruit 120 participants who will be randomised to one of four arms: either IHL-675A, CBD alone, HCQ alone or placebo.

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

Over the 24-week period, participants will record their pain and function outcomes daily by completing questionnaires on pain, fatigue, joint stiffness and quality of life.

An electronic Patient Reported Outcomes device, similar to completing a questionnaire on an electronic tablet, will be used to record their responses.

Participants will also attend monthly visits at the clinical trial site, where blood tests, and physical examinations are carried out to monitor additional safety and efficacy outcomes including inflammatory biomarkers.

In addition, the trial will also include a sub-study examining joint damage via magnetic resonance imaging (MRI).

After the 24-week period, there will be an option for participants to roll over into the open label extension study, where all eligible participants will receive IHL-675A for a further 24 weeks regardless of the initial treatment arm allocated in the first 24 weeks.

Incannex says the results of this study will establish the safety and efficacy of IHL-675A and contribute to the combination rule assessment in a FDA505(b)2 new drug application dossier.

“Arthritis is a disease that negatively impacts the well- being of millions of people worldwide and this trial is a big step toward Incannex potentially improving quality of life for these patients,” said Bleackley.

“We look forward to continuing to build our research relationship with Avance Clinical, who did an outstanding job managing the Phase-1 clinical trial assessing the tolerability and pharmacokinetics of IHL-675A in healthy volunteers.”

Multiple billion dollar potential for IHL-675A

IHL-675A’s active ingredients comprise a combination of HCQ, an expired patent registered pharmaceutical drug, and CBD.

HCQ has been well known to regulate the activity of the immune system and modify the underlying disease process rather than simply treating the symptoms.

Incannex has demonstrated that CBD and HCQ together can act synergistically to inhibit production of key inflammatory cytokines.

As a result, Incannex believes that IHL-675A can be a multi-use drug candidate suitable for treating a number of other inflammatory diseases.

The company says it wants to focus the drug initially on three indications: rheumatoid arthritis, inflammatory lung conditions (acute respiratory distress syndrome, COPD, asthma, and bronchitis), and inflammatory bowel disease.

Reports suggest the treatment of these indications have a combined global annual market size exceeding US$125 billion per annum.

IHL has also completed a pre-IND meeting with the FDA to discuss the regulatory pathway for the development of IHL-675A in the US, and plans to open INDs for each of the three indications.

The FDA has agreed  that marketing applications for IHL-675A should be under a 505(b)(2) application, due to the existence of historical studies that Incannex is entitled to use in the new drug application.

Apart from this program, Incannex has a rich pipeline of 28 R&D projects, including a Phase-2 clinical trial to assess its psilocybin-assisted psychotherapy for treatment  of  generalised  anxiety disorder  (GAD).

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.