KINECT-HD Trial in Progress
Erin Furr Stimming, MD, is Director of the HDSA Center of Excellence, and associate professor of neurology at The University of Texas Health Science Center at Houston.
What is KINECT-HD?
KINECT-HD is a phase 3, randomized, double-blind, placebo-controlled trial to assess the efficacy, safety, and tolerability of valbenazine for the treatment of chorea associated with HD. FDA approved in 2017 for tardive dyskinesia, valbenazine is a VMAT2 inhibitor, the third in this class being studied for chorea in HD. The primary endpoint of KINECT-HD is the change in the total maximal chorea (TMC) score from screening/baseline to maintenance (the average of the Week 10 and Week 12 assessments).
Secondary study objectives include the Clinical Global Impression of Change (CGI-C), the Patient Global Impression of Change (PGI-C), and the Quality of Life in Neurological Disorders (Neuro-QoL) Upper and Lower Extremity Function Short Form.
KINECT-HD is conducting ongoing enrollment of a total of 120 subjects with motor manifest HD from North America and Canada at 46 HSG study sites. The study duration is approximately 18 weeks and includes nine study visits. KINECT-HD2 is an open label rollover study that will allow participants from KINECT-HD to receive valbenazine for up to 104 weeks while assessing safety, tolerability and efficacy.
Why should we study yet another VMAT2 inhibitor for HD related chorea? I believe there are a number of reasons:
1) Expand approved treatment options for individuals with HD
There remains an unmet medical need for the symptomatic treatment of chorea. Schultz et al. studied the Enroll-HD dataset as of April 2018 and found only 137 of 1,612 eligible subjects received tetrabenazine, while 104 used risperidone and 158 olanzapine.<sup>1</sup> A more recent Enroll-HD analysis found that <25% of HD patients with chorea actually receive treatment.<sup>2</sup> The unique pharmacokinetic profile of valbenazine allows for once daily dosing and low peak to trough fluctuations. The terminal half-life for valbenazine and its metabolite is approximately ~20 hours, which differs significantly from deutetrabenazine (~8 hours) and tetrabenazine (~4 hours). Importantly, valbenazine’s sole metabolite (+ alpha DHTBZ) has the highest affinity and selectivity for VMAT2.<sup>3</sup> Medications are often cost-prohibitive or cost-offensive at best. We have a higher likelihood of achieving cost coverage for medications that are prescribed on label. This is yet another reason — even within the same class — to provide patients with additional therapeutic options.
2) Provide more opportunities for individuals with HD to participate in clinical trials
The process of pursuing an approval for a new indication is arduous. However, it provides a chance for individuals with HD to participate in the process, be part of the solution and to feel empowered. Das Mahapatra et al. published results from an online patient directed survey that found the most important considerations in trial participation were altruistic: an opportunity to improve one’s own health and that of others. <sup>4</sup>
3) Explore new outcome measures for HD clinical trials
A subpopulation of study subjects in KINECT-HD will apply wearable sensors to help objectively determine how study participants are responding while not in the clinic. This enhances our understanding of the impact of chorea in a “real world” setting. Moreover, applying scales that assess quality of life (QoL) can help us better determine the impact chorea has on various QoL measures.
We are profoundly grateful to the HD community for their participation in KINECT-HD and KINECT-HD2. Every trial is important in advancing our knowledge of and treatment for HD. We must continue to strive for improved symptomatic treatments for individuals currently struggling with HD.
Further information about the study, including study site locations, can be found at the HSG Website (https://huntingtonstudygroup.org/current-clinical-trials/kinect-hd/) and at www.clinicaltrials.gov.