The primary efficacy endpoint for this study was the change from baseline to Week 65 in the TFC (defined as the sum of all TFC 5-items ratings [domestic chores, activities of daily living, finances, care level, and occupation]). The TFC is the standard and well-accepted clinical scale for staging and tracking the progression of HD using functional capacity. Scores range from 0 to 13, with 13 as the least affected and 0 as complete incapacity.

The modified intent to treat (mITT) population included all participants in the ITT population who received at least one dose of study drug and had valid in clinic TFC scores both at baseline and at least one post-baseline timepoint. The mITT population was analyzed according to the treatment to which the participant was randomized.

The mITT population was the main analysis population for the primary endpoint in non-EMA regions. Note that the analysis was based on observed data.

The primary efficacy endpoint for this study was the change from baseline to Week 65 in the TFC (defined as the sum of all TFC 5-items ratings [domestic chores, activities of daily living, finances, care level, and occupation]). The TFC is the standard and well-accepted clinical scale for staging and tracking the progression of HD using functional capacity. Scores range from 0 to 13, with 13 as the least affected and 0 as complete incapacity.

The intent to treat (ITT) population included all randomized participants. The ITT population was analyzed according to the treatment to which the participant was randomized.

The ITT population was the main analysis population for the primary endpoint in the EMA region.

The composite Unified Huntington Disease Rating Scale (cUHDRS) uses 4 components:

Total Motor Score (TMS) assesses motor features (oculomotor, dysarthria, chorea, dystonia, gait, postural stability). Higher score = worse outcome. Best score=0. Worst score= 124.

Stroop Word Reading (SWR) measures attention and mental flexibility. Pat. reads names of colors printed in black ink. Scores reflect correct responses in 45 sec. Higher score = better outcome. Best score=100. Worst score=0.

Symbol Digit Modalities Test (SDMT) tests psychomotor speed and working memory. Participant has 90 sec to match numbers with symbols. Scores = correct answers in 90 sec. Higher score = better outcome. Best score=120. Worst score=0.

Total Functional Capacity (TFC) tests the capacity to maintain daily living, finances, care level, occupation. Higher score = better outcome. Best score=13. Worst score=0.

Total integrated cUHDRS scale range: -7.6 to 24.8. The higher, the better.

The modified intent to treat (mITT) population included all participants in the ITT population who received at least one dose of study drug and had valid in-clinic TFC scores both at baseline and at least one post-baseline timepoint. The mITT population was analyzed according to the treatment to which the participant was randomized. Note that the analysis was based on as observed data only, patient numbers are therefore lower.

The composite Unified Huntington Disease Rating Scale (cUHDRS) assesses 4 components (see secondary outcome for details):

Total Motor Score (TMS) for motor features. Higher score = worse outcome. Worst = 124.

Stroop Word Reading (SWR) measures attention and mental flexibility. Higher score = better outcome.

Symbol Digit Modalities Test (SDMT) tests psychomotor speed and working memory. Higher score = better outcome.

Total Functional Capacity (TFC) tests the capacity to maintain daily living, finances, care level, occupation. The higher, the better.

Total cUHDRS scale range: -7.6 to 24.8 (assuming 150 as the max score of SWR). The higher, the better.

This sensitivity analysis was performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Quantitative (Q)-motor is a clinical assessment of fine motor skills. It is based on the application of pre-calibrated and temperature-controlled force transducers and 3-dimensional position sensors. The index finger is positioned above a force transducer and is to tap as fast as possible. The start was defined as a rise of the force by 0.05 Newton above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. The IOI refers to the time between the onset of consecutive taps (the faster, the better).

In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Quantitative (Q)-motor is a clinical assessment of fine motor skills that are crucial for daily activities. It is based on the application of pre-calibrated and temperature-controlled force transducers and 3-dimensional position sensors. Pronation/Supination assesses the regularity of hand taps. The force and duration of the hand taps were recorded similarly to the speeded tapping task. One pronation/supination hand tapping measure is ITI (the faster, the better).

In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Quantitative (Q)-motor is a clinical assessment of fine motor skills that are crucial for daily activities. It is based on the application of pre-calibrated and temperature-controlled force transducers and 3-dimensional position sensors. Pronation/Supination assess the regularity of hand taps. The force and duration of the hand taps were recorded similarly to the speeded tapping task. One pronation/supination hand tapping measure is IOI (the faster, the better).

In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Total Functional Capacity (TFC) tests the capacity to maintain domestic chores, activities of daily living, finances, care level, and occupation. Scores from 0 - 13. Higher score = better outcome.

In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Stroop Word Reading (SWR) measures attention and mental flexibility. Pat. reads names of colors printed in black ink. Scores reflect correct responses in 45 sec. Higher score = better outcome.

In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Symbol Digit Modalities Test (SDMT) tests psychomotor speed and working memory. Participant has 90 sec to write match numbers with symbols. Scoring sums correct substitutions in 90 second interval (max = 110). Higher score = better outcome.

In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Total Motor Score (TMS) assesses motor features (oculomotor, dysarthria, chorea, dystonia, gait, postural stability). Each rated 0 (normal) - 4 (abnormal). Higher score = worse outcome. Worst = 124.

In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.