In Brief: Q-Motor in PROOF-HD

Posted on at May 11, 2021
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Q-Motor in PROOF-HD:
Objective evidence for effect of pridopidine


Ralf Reilmann, MD, PhD is the Global Coordinating Principal Investigator – Europe, for PROOF-HD.

Q-Motor (Quantitative-Motor) assessments have been applied in multiple clinical trials and biomarker studies in HD. In PRIDE-HD, several Q-Motor measures provided evidence for a motor benefit of patients treated with pridopidine – particularly in the 45 mg BID arm – see figure below (modified from Reilmann et al., 2019). In contrast, the placebo group showed deterioration, i.e. progression of motor symptoms. This observation corroborated the Total Functional Capacity (TFC) effect observed at 45mg BID.

Jointly, the data supported a central effect of pridopidine and provided the rational for embarking into the PROOF-HD phase III study. It was very helpful to have these observation at hand, particularly in light of the changes seen in the Unified Huntington’s Disease Rating Scale – Total Motor Score (UHDRS-TMS). The standardized, objective Q-Motor data supported the interpretation that a strong placebo effect had driven the large TMS benefits observed in the placebo group in PRIDE-HD. While Q-Motor measures are not yet validated and accepted as a primary endpoint by regulatory bodies, agencies such as the Federal Institute for Drugs and Medical Devices in Germany did acknowledge the supportive evidence they may provide for a primary endpoint in pivotal clinical trials. Therefore, Q-Motor assessments were also implemented in PROOF-HD.


Q-Motor is an outpatient clinic-based assessment that is easy to use at no relevant risk or burden for patients. Assessments selected for PROOF-HD will take approximately 5-10 minutes. The data is transferred automatically online to the George-Huntington-Institute/QuantiMedis Q-Motor team in Germany for ongoing quality control and blinded analyses. It can be used for efficacy and safety analysis and help trigger decisions in adaptive clinical trial designs (not implemented in PROOF-HD). Online training to study coordinators in live sessions is provided by the Q-Motor team, available 24/7. Changes in Q-Motor were observed in premanifest HD gene carriers up to two decades before HD onset in the Cure Huntington’s Disease Initiative (CHDI)-funded study TRACK-HD.


In essence, Q-Motor was developed in the HD community and originally explored at the HDSA Center of Excellence at Columbia University in New York during a post-doc I did between 1997 and 2001. Encouraged by early results, the development of more refined assessments and setups was initiated and funded by several sources. After implementation in TRACK-HD, Q-Motor was employed in clinical trials, e.g. the AFQ056 study (Novartis), AMARYLLIS (Pfizer), LEGATO-HD (Teva), PRIDE-HD (Teva) SIGNAL (Vaccinex), and the first HD gene therapy trial, HD·GeneTX1 (uniQure).

Feedback from the over 100 sites that used Q-Motor globally allowed the development of “Q-Motor 2.0.” It is installed on a mobile cart and can easily be moved to different places. The novel platform was expanded to also provide cognitive assessments such as the Trail-Making Test A and B and others such as the “Q-Cog” assessments that were developed with funding from the European Union.

Correlation of Q-Motor measures with MRI volumes, CAG repeat-based disease burden scores, and clinical assessments such as the TFC or UHDRS-TMS were observed in multiple trials. Evidence of the clinical significance of these measures is evolving, and studies like PROOF-HD help us learn what contributions these measures may make. Besides use in symptomatic HD cohorts, the sensitivity in prodromal and premanifest groups holds promise to facilitate development of preventive HD therapies in prodromal stages, which could also be interesting for a well-tolerated drug as pridopidine.



Reilmann R, McGarry A, Grachev ID, Savola JM, Borowsky B, Eyal E, Gross N, Langbehn D, Schubert R, Wickenberg AT, Papapetropoulos S, Hayden M, Squitieri F, Kieburtz K, Landwehrmeyer GB (2019) Safety and efficacy of pridopidine in patients with Huntington’s disease (PRIDE-HD): a phase 2, randomised, placebo-controlled, multicentre, dose-ranging study. Lancet Neurol 18:165-176.


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