One of the four approved pathways to supply Medicinal Cannabis in Australia is via Medicinal Cannabis Clinical Trails under the CTN scheme. This blog discusses this route in greater detail.
The use of Medicinal Cannabis in the treatment and relief of symptoms of chronic conditions has historically, always been a controversial topic. The concern stems partly from a safety and efficacy perspective, in addition to the well-touted idea that Cannabis could be a “gateway drug,” (the abuse rates for opioid-based medication notwithstanding).
Despite the legalisation of Medicinal Cannabis, the regulatory response has been somewhat slow. Up to date, the TGA have only approved one cannabinoid-
containing product (Sativex/Nabiximol, listed in the ARTG as ID 181978)a prescription-only medicine for the relief of muscle stiffness in multiple sclerosis.
The most common methods to access Medicinal Cannabis Products are through two regulatory pathways:
- the Special Access Scheme (or Compassionate Supply), or
- prescription via an Authorised Prescriber.
However, these pathways have one major limitation: there is no formal way to observe and collect any statistically significant data regarding the products’ safety and efficacy. This is where Clinical Trials come in.
Clinical Trials provide a framework via specifically designed studies, that allows access to Medicinal Cannabis while also collecting critical data which can be used to address key clinical endpoints regarding safety and efficacy of the products in question.
Whether the medicinal cannabis formulation contains a mix of THC & CBD, or CBD only, there are two regulatory pathways that prospective manufacturers can consider to conduct clinical trials in Australia:
- Clinical Trial Exemption (CTX) scheme, and
- Clinical Trial Notification (CTN) scheme
Clinical Trial Notification Scheme (CTN)
The most commonly used scheme is the CTN, under which the sponsor notifies the TGA for their intention to conduct a clinical trial (after approval of the proposed trial from a Human Research Ethics Committee or HREC). This scheme is a unique regulatory mechanism available only in Australia, as the TGA is not involved directly in reviewing and evaluating the safety of the tested product; the HREC plays a pivotal role in reviewing and approving the study proposal.
The HREC requires the sponsor to provide:
- copies of the study protocol
- Informed Consent for all the patients involved
- the Investigator’s Brochure (IB), and
- any information or letters that will be provided to the volunteers, including any advertising material that the sponsor intends to use for recruitment (paper and media ads, video, radio scripts etc).
HREC will review the scientific justification for the study and study design, including what type of clinical and safety data will be collected, how and when data will be collected, what safety measures will be taken to ensure the safety of the participants, and the Product Information currently available for safety and efficacy.
Even though TGA does not review the proposed study under the CTN scheme, the sponsor of the proposed clinical trial and the HREC have a legal obligation to ensure that the study will comply with the National Statement (NHMRC 2007), the current World Medical Association Declaration of Helsinki, and the GCP requirements annotated with TGA comments.
Due to the nature and novelty of medicinal cannabis products, special considerations would need to be taken when designing a clinical trial, including:
- study design – number of participants to be recruited; patients or healthy volunteers; number of cohorts
- safety monitoring.
- blinded randomised or open label study.
- clinical and safety study end points.
- exclusion/inclusion criteria – whether to include psychiatric assessment of the participants, for example.
Other important aspects include:
- the currently available safety and efficacy data for the medicinal cannabis formulation(s) intended to be tested,
- permit/licence conditions for supply, storage and dispensing of medicinal cannabis and
- the ability of the Clinical Research Organisation (Clinical unit) to recruit the required number of volunteers.
The quality of the medicinal cannabis formulation products used in clinical trials must, at minimum, comply with the requirements published by TGA in the guidance TGO 93. The expected quality standards include requirements for product characterization, manufacturing, facilities, validation, starting material considerations, specifications, stability, potency, purity/impurities, and the complexity of the cannabis product. PIC/S Part I of the GMO Guide is also be applicable for final products.
Indeed, a conduct of a Clinical Trial under CTN using medicinal cannabis formulation is not a trivial matter. It requires careful considerations for study design, ensuring safety of the participants, evaluation of the Product Information, assessing the risk of any adverse events and any associated pharmacovigilance activities, choosing the Contract Research Organisation, as well as evaluating the actual formulation of product and GMP requirements.
Medicinal cannabis products are currently being investigated for the treatment of a variety of different conditions that range from alleviating symptoms associated with advanced stages of cancer, HIV/AIDS, epilepsy, and ulcerative colitis, to the treatment of severe acne vulgaris. Clinical trial information can be viewed at the Australian and New Zealand Clinical Trials Registry (ANZCTR) as well as the US National Library of Medicine. The potential for using Medicinal Cannabis products across these different conditions seems very promising, nevertheless, the road for developing safe and efficient products is not always straightforward. As more information becomes available through data derived from Medicinal Cannabis Clinical Trials, it could mean that other challenges arise which would need to be overcome.
If you need help with setting up a CTN clinical trial, PharmOut can help, please contact us at one of our offices around the world for more information.
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