Clinical trial timeline
SPG4 clinical drug trial
The Research Program update on the clinical trial for December 2020 can be viewed as a video. Read the full report below for more about other parts of the research program.
The graphic below outlines the recent, current and future development of the SPG4 clinical trial program. The process looks deceptively simple at this high level look, but inside each of these boxes on the graphic is an ocean of depth and a mountain of detail.
The current efforts remain focused on the methodical determination and selection of the highest value assessments and measures for use in the phase 2a trial. As with so much of this 10 year+ research program, the scientific work is pioneering and discovery learning, including what different assessments (such as spasticity, strength, balance, various aspects of gait and so on) amongst the numerous possibilities are likely to provide the best guidance in determining drug treatment effectiveness. Assessments will be evaluated individually as well as part of a composite measure. Another important consideration in planning the raft of assessments and measures for the phase 2a trial is the likely impact on participants… how long clinic visits will take and how demanding they will be on people.
The drug manufacture and supply process is complex and is taking longer than expected to identify a suitable supplier. As this can’t be done in Australia, the global pandemic appears to be interrupting and delaying the supply chain. Every dose needs to be identical in every respect across the full range of doses of the active ingredient from zero to a determined maximum. Not only does the company and particular manufacturing site have to be certified to an international standard, but quality testing of the active pharmaceutical ingredient (API) is rigorous throughout the manufacturing process.
Formal documentation (Synopsis and Protocol) is ongoing so it will not take much to finalise once all the necessary upstream decisions are made regarding the choice of assessments and drug supply. Once completed, the documentation is submitted seeking approval to conduct the clinical trial.
Even though the graphic shows the phase 2a trial beginning in the second half of next year, what are called ‘baseline measures’ of participants will get underway as soon as possible in 2021 to assess participants’ HSP status before receiving medication. The reason for this is that treatment effectiveness is an individual assessment for each participant. It is based on the changes that occur for the individual from the start to the end of the trial, so it is necessary to assess HSP status and rate of progression leading into the trial.
Blood biomarker (Sydney)
We have developed a test (assay) that can detect the effect of Noscapine treatment on a biomarker compound of microtubule dynamics in blood. Our previous experiments had shown that the effect of noscapine on blood cells (PBMCs) can be detected after 16hrs of in vitro (laboratory dish) treatment. In view of the needs for the upcoming clinical trial, we have now achieved a reduction down to 3 hrs to detect the noscapine treatment effect.
We have been working on further modifying our blood biomarker assay for clinical trial applications. We have tested multiple sample collection protocols and have now identified the optimal option. Initial sample processing involved 12-14 steps and took 2-3 hours for each sample. This has now been refined to a one-step 20-minute process (protocol). This approach increases sample viability and is efficient when processing large numbers of samples making it ideal for clinical trial testing.
We are now work on adapting our assay to a high-throughput assay setting necessary for batch sample analysis. This allows samples to be analysed in a single assay run, avoiding sample-to-sample variation providing more reliable results, and is time and cost-effective. For comparison, when processing samples individually, there can be significant sample-to-sample variation, so each sample would be tested up to 3 times to provide reliability and confidence in the results. In high-throughput batch sample analysis, all samples are analysed simultaneously and analytical process variation between samples is eliminated.
Skin fibroblast biomarker (Sydney)
We are applying a novel machine-learning-guided, high-content microscopy image analysis approach to HSP and control skin fibroblast samples. We are presently analysing data and working towards preparing a manuscript.
Using skin fibroblasts (skin cells grown from a skin tissue sample) the aim is to develop a biomarker to aid in HSP diagnosis and drug testing. A machine-learning-guided, high-content microscopy image analysis approach to comparing HSP and healthy (control) skin fibroblast samples is being developed. Analysis of experimental data is continuing and a scientific paper for publication is in preparation. (Dr. Wali also leads this study)
Grant funding applications
Two grant funding applications were submitted in November to the NHMRC for a Phase 2b clinical trial. The lead time for grant funding is such that now is the time to be applying for funding for trials commencing in 2022.