Many people living with ALS and their families want to know how scientific discoveries move from basic research in the laboratory through different phases of clinical trials using human volunteers. They also want to understand why clinical research is required before a new therapy is approved and why it takes so long for researchers to determine if a promising new treatment works.

Dr. David Taylor, Vice President of Research at ALS Canada discussed these topics and more during a lively webinar presentation about clinical trials on June 29, 2017. The webinar was the second of four presentations in the ALS Canada Webinar Series to provide an update on the latest ALS research, clinical trials and funding programs.

How are researchers improving clinical trial design to find better answers, faster? What are the best resources for finding reputable information about treatment options? Which clinical trials are recruiting participants? What are some of the most promising trials underway? Dr. Taylor addressed these questions and many more.

The Spectrum of Research Discovery

At the beginning of the research discovery spectrum, scientists conduct preclinical research in the laboratory, looking for new understandings about the biology of the disease, designing new therapies that address how the disease works and conducting studies in cells or animals such as mice, rats, fish, flies or worms. These animal models have a simpler biological structure than humans, which helps researchers to better understand how a potential therapy works in a very general way and what the side effects are.

Before a new therapy can advance from the laboratory to human clinical trials, a lot of work takes place to ensure it will be safe to test in people. Researchers must apply to Health Canada for approval, showing data from toxicity studies in animal models and how they expect the drug will be processed by the human body.

After approval to proceed, clinical trials move through Phases 1, 2 and 3 in order, as long as a drug or intervention continues to show strong results. Participants visit a clinical trial site, usually a hospital or medical clinic, to receive an assigned treatment. Researchers measure their progress by collecting information about how their body is reacting to the intervention. The study objectives, the number of participants, cost and timing vary for each phase:

Why Does It Take So Long?

As you can see from the table above, it can take five to eight years or more for a new therapy to move through all three clinical research phases. Why does it take so long? Because each phase involves securing approvals and funding, establishing study sites, finding and screening patients that meet the eligibility criteria for what’s being tested, and collecting and analyzing the data.

After Phase 3, if the evidence shows that a new therapy can slow disease progression, the drug manufacturer decides whether to apply to Health Canada for market approval. Expedited review for a drug application takes about six to 12 months. After that, each province may take an additional two years or more to decide whether to cover the cost of the drug.

In the event of a positive Phase 3 trial, ALS Canada will advocate with drug manufacturers and Health Canada to help expedite the process of making the treatment available to Canadians and to have costs covered.

Designing Clinical Trials to Ensure Answers

Clinical trials must be designed properly to ensure collecting the right information about whether a new therapy is safe, and if it works or doesn’t work.

Given the wide variability in the rate of disease progression among people with ALS, researchers are exploring new indicators to measure responses to therapies in clinical trials. The ALS Functional Rating Scale – Revised (ALSFRS-R) remains the most common outcome measure, but a range of new measures for functional abilities in the clinic and using consumer wearables or mobile apps are currently being examined.

Biomarkers, biological markers in tissue or blood, have been identified recently as essential for improving clinical trial design. One way they can be used is to screen patients to ensure inclusion of those most likely to benefit in a trial. For example, in the new trial of NP001 in progress, participants are pre-screened for C-reactive protein, a known biomarker for inflammation. Beyond this specific example, biomarkers are crucial to the success of ALS clinical trials in general because they explain whether the therapy is doing what it’s expected to. Without knowing this, it becomes very difficult to interpret results.

Beware Unproven Treatments Found on the Internet!

It’s easy to find alternative treatments for ALS promoted on the Internet, but unfortunately, many are unproven, or worse, unsafe. ALSUntangled is an excellent resource for determining if an alternative treatment is based on sound science. ALSUntangled is led by Dr. Richard S. Bedlack, Duke University ALS Clinic Director and sponsored by the ALS Association and the Motor Neurone Disease Association. Dr. Bedlack and a team of ALS researchers evaluate the science behind alternative treatment claims and issue a comprehensive review of the potential mechanism of action, the available evidence and risks. Dr. Bedlack will be discussing ALSUntangled at the ALS Canada Virtual Research Forum coming up in August 2017.

How to Find a Reputable Clinical Trial for ALS How to Find a Reputable Clinical Trial for ALS 
The best sources for finding reputable information about treatments that have already been tested, or to find a clinical trial that is currently recruiting new participants are:

Clinical Trials to Watch

Phase 3 trials for masitinib, NurOwn® and tirasemtiv are ones to watch closely. Dr. Taylor spoke about these clinical trials and others during the first webinar.

ALS Canada Virtual Research Forum

ALS Canada will host a Virtual Research Forum on Wednesday, August 9 and Thursday, August 10, 2017 from 11:00 a.m. – 5:00 p.m. Eastern time. The forum is free and open to anyone interested in learning more about ALS research currently underway and therapies in development. Hosted by Dr. David Taylor, the forum will feature more than 20 speakers and panelists over two days. Advance registration is recommended as spots are limited. Learn more and register here.

Read more about the ALS Canada Research Program and consider making a donation today.

 

Posted in: Research