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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05021978




Registration number
NCT05021978
Ethics application status
Date submitted
20/08/2021
Date registered
26/08/2021
Date last updated
1/03/2024

Titles & IDs
Public title
A Clinical Trial of PRAX-944 in Participants With Essential Tremor
Scientific title
A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults With Essential Tremor
Secondary ID [1] 0 0
PRAX-944-221
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Essential Tremor 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Part A: 20 and 40 mg PRAX-944
Treatment: Drugs - Part B: 120 mg PRAX-944
Treatment: Drugs - Part B: 120 mg PRAX-944 and Placebo

Experimental: Part A: Open-label 20 and 40 mg PRAX-944 - Once daily, oral dosing with 7 days of 20 mg and 7 days of 40 mg

Experimental: Part B: Open-label titration PRAX-944 (120 mg) followed by blinded PRAX-944 - Once daily, oral dosing with titration to 120 mg: 3 days of 20 mg, 4 days of 40 mg, 7 days of 60 mg, 7 days of 80 mg, 7 days of 100 mg, 28 days of 120 mg

Active comparator: Part B: Open-label titration PRAX-944 (120 mg) followed by blinded placebo - Once daily, oral dosing with titration to 120 mg: 3 days of 20 mg, 4 days of 40 mg, 7 days of 60 mg, 7 days of 80 mg, 7 days of 100 mg, 14 days of 120 mg, 14 days placebo


Treatment: Drugs: Part A: 20 and 40 mg PRAX-944
Once daily oral treatment

Treatment: Drugs: Part B: 120 mg PRAX-944
Once daily oral treatment with titration

Treatment: Drugs: Part B: 120 mg PRAX-944 and Placebo
Once daily oral treatment with titration followed by placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score
Assessment method [1] 0 0
The TETRAS upper limb score is calculated as the sum of the 6 separate upper-limb maneuvers assessed by the clinician: forward-outstretched postural tremor \[right\], forward outstretched postural tremor \[left\], lateral wing-beating postural tremor \[right\], lateral wing-beating postural tremor \[left\], kinetic tremor \[right\], kinetic tremor \[left\], each on a 0 (no tremor) to 4 (maximum tremor) severity scale in 0.5-point increments. TETRAS Part 4 score for both upper limbs ranged from 0 to 24, higher scores indicated more severe tremor. A negative change from baseline indicated less tremor. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Timepoint [1] 0 0
Baseline (Day 0), Days 7 and 14
Primary outcome [2] 0 0
Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation
Assessment method [2] 0 0
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Incidence and Severity of Adverse Events have been reported.
Timepoint [2] 0 0
Up to Day 70
Primary outcome [3] 0 0
Part B: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters
Assessment method [3] 0 0
Vital signs parameters included body temperature, pulse rate, respiratory rate, blood pressure (systolic and diastolic), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals). Any change in vital sign abnormalities that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported as an unsolicited adverse event (AE). Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.
Timepoint [3] 0 0
Up to Day 70
Primary outcome [4] 0 0
Part B: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)
Assessment method [4] 0 0
The C-SSRS is described as a scale developed at Columbia University that has 2-6 questions each in categories of Suicidal Ideation, Intensity of Ideation, Suicidal Behavior, and Actual Attempts. Four constructs were measured. Severity of Suicidal ideation is rated on a 5-point ordinal scale. Intensity of ideation is comprised of 5 items (frequency, duration, controllability, deterrents, and reason for ideation), each rated on a 5-point ordinal scale. Suicidal behavior is rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. Lethality, assesses actual attempts; actual lethality is rated on a 6-point ordinal scale, and if actual lethality is 0, potential lethality of attempts is rated on a 3-point ordinal scale.The higher the C-SSRS score, the higher the suicide risk (ie. worse outcome).
Timepoint [4] 0 0
Up to Day 70
Secondary outcome [1] 0 0
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale
Assessment method [1] 0 0
The TETRAS is an essential tremor and activities of daily living rating scale. The full scale has 2 sections, the Performance subscale (PS) and the ADL subscale. The PS consists of 9 items covering different body regions. These 9 items are rated on a 5-point scale (ranging from 0 to 4). One item, Item 4, consists of ratings for 3 tasks rated separately for upper limbs on both sides of the body for a total of 6 ratings. The total score of the 9 items (14 ratings) ranges from 0 to 70 with higher scores indicating greater tremor severity. The total score and individual item ratings will be evaluated as outcomes in this trial. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug.
Timepoint [1] 0 0
Baseline (Day 0), Days 7 and 14
Secondary outcome [2] 0 0
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry
Assessment method [2] 0 0
Accelerometer was used to evaluate record coordinates and accelerations in the 3D space over time. The 3 maneuvers in the upper limb item will be completed for both arms, first for the right arm and then for the left. Each upper limb sub-item is scored on a scale from 0 to 4 including to 0.1 increments. The accelerometer upper limb total score, ranges from 0 to 24. A decrease in score is indicative of improvement. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Timepoint [2] 0 0
Baseline (Day 0), Days 7 and 14
Secondary outcome [3] 0 0
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting)
Assessment method [3] 0 0
The TETRAS ADL subscale is a 12-item assessment of typical daily activities that are impacted by tremor. Activities are assessed in the following functional domains: speaking, feeding, drinking, personal hygiene, dressing, writing, and social activity. The impact to each function is rated on a 5-point Likert scale from 0 to 4. The ADL subscale score is calculated as the sum of all 12 items and ranges from 0 to 48 with higher scores reflecting higher impact. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Timepoint [3] 0 0
Baseline (Day 0), Days 7 and 14
Secondary outcome [4] 0 0
Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation
Assessment method [4] 0 0
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Incidence and Severity of Adverse Events have been reported.
Timepoint [4] 0 0
Up to Day 21
Secondary outcome [5] 0 0
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters
Assessment method [5] 0 0
Vital signs parameters included body temperature, pulse rate, respiratory rate, blood pressure (systolic and diastolic), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals). Any change in vital sign abnormalities that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported as an unsolicited adverse event (AE). Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.
Timepoint [5] 0 0
Up to Day 21
Secondary outcome [6] 0 0
Part A: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)
Assessment method [6] 0 0
The C-SSRS is described as a scale developed at Columbia University that has 2-6 questions each in categories of Suicidal Ideation, Intensity of Ideation, Suicidal Behavior, and Actual Attempts. Four constructs were measured. Severity of Suicidal ideation is rated on a 5-point ordinal scale. Intensity of ideation is comprised of 5 items (frequency, duration, controllability, deterrents, and reason for ideation), each rated on a 5-point ordinal scale. Suicidal behavior is rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. Lethality, assesses actual attempts; actual lethality is rated on a 6-point ordinal scale, and if actual lethality is 0, potential lethality of attempts is rated on a 3-point ordinal scale.The higher the C-SSRS score, the higher the suicide risk (ie. worse outcome).
Timepoint [6] 0 0
Up to Day 21
Secondary outcome [7] 0 0
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase
Assessment method [7] 0 0
The TETRAS upper limb score is calculated as the sum of the 6 separate upper-limb maneuvers assessed by the clinician: forward-outstretched postural tremor \[right\], forward outstretched postural tremor \[left\], lateral wing-beating postural tremor \[right\], lateral wing-beating postural tremor \[left\], kinetic tremor \[right\], kinetic tremor \[left\], each on a 0 (no tremor) to 4 (maximum tremor) severity scale in 0.5-point increments. TETRAS Part 4 score for both upper limbs ranged from 0 to 24, higher scores indicated more severe tremor. A negative change from baseline indicated less tremor. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Timepoint [7] 0 0
Baseline (Day 0) and Day 42
Secondary outcome [8] 0 0
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase
Assessment method [8] 0 0
The TETRAS upper limb score is calculated as the sum of the 6 separate upper-limb maneuvers assessed by the clinician: forward-outstretched postural tremor \[right\], forward outstretched postural tremor \[left\], lateral wing-beating postural tremor \[right\], lateral wing-beating postural tremor \[left\], kinetic tremor \[right\], kinetic tremor \[left\], each on a 0 (no tremor) to 4 (maximum tremor) severity scale in 0.5-point increments. TETRAS Part 4 score for both upper limbs ranged from 0 to 24, higher scores indicated more severe tremor. A negative change from baseline indicated less tremor. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Timepoint [8] 0 0
Baseline (Day 0), Days 7 and 21
Secondary outcome [9] 0 0
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale During OLT Phase
Assessment method [9] 0 0
TETRAS Performance Subscale was used to assess essential tremor as scored by the independent video raters. The performance subscale consists of 9 items, i.e. item 1 (head), item 2 (face), item 3 (voice), each of the 6 sub-items for item 4 (upper limb), the maximum of the 4 sub-items for item 5 (lower limb), 2 sub-items (right and left side) for item 6 (Archimedes spirals), item 7 (handwriting), 2 sub-items (right and left side) for item 8 (dot approximation), and item 9 (standing) for a total score ranging from 0 to 64 from 16 sub-items. Each item is rated on a scale of 0 to 4, including 0.5 increments. A lower score is indicative of improvement. The total score has been presented. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Timepoint [9] 0 0
Baseline (Day 0) and Days 7, 21 and 42
Secondary outcome [10] 0 0
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry During OLT Phase
Assessment method [10] 0 0
Accelerometer was used to evaluate record coordinates and accelerations in the 3D space over time. The 3 maneuvers in the upper limb item will be completed for both arms, first for the right arm and then for the left. Each upper limb sub-item is scored on a scale from 0 to 4 including to 0.1 increments. The accelerometer upper limb total score, ranges from 0 to 24. A decrease in score is indicative of improvement. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Timepoint [10] 0 0
Baseline (Day 0), and Days 7, 21 and 42
Secondary outcome [11] 0 0
Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting)
Assessment method [11] 0 0
TETRAS Performance Subscale was used to assess essential tremor as scored by the independent video raters. The performance subscale consists of 9 items, i.e. item 1 (head), item 2 (face), item 3 (voice), each of the 6 sub-items for item 4 (upper limb), the maximum of the 4 sub-items for item 5 (lower limb), 2 sub-items (right and left side) for item 6 (Archimedes spirals), item 7 (handwriting), 2 sub-items (right and left side) for item 8 (dot approximation), and item 9 (standing) for a total score ranging from 0 to 64 from 16 sub-items. Each item is rated on a scale of 0 to 4, including 0.5 increments. A lower score is indicative of improvement. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Timepoint [11] 0 0
Baseline (Day 0), Days 7, 21 and 42
Secondary outcome [12] 0 0
Part B: Change From Baseline in TETRAS Activities of Daily Living (ADL) Score
Assessment method [12] 0 0
The TETRAS ADL subscale is a 12-item assessment of typical daily activities that are impacted by tremor. Activities are assessed in the following functional domains: speaking, feeding, drinking, personal hygiene, dressing, writing, and social activity. The impact to each function is rated on a 5-point Likert scale from 0 to 4. The ADL subscale score is calculated as the sum of all 12 items and ranges from 0 to 48 with higher scores reflecting higher impact. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Timepoint [12] 0 0
Baseline (Day 0), Days 7, 21 and 42
Secondary outcome [13] 0 0
Part B: Change From Baseline in Quality of Life in Essential Tremor Questionnaire (QUEST) Total Scores.
Assessment method [13] 0 0
Quality of Life in Essential Tremor Questionnaire (QUEST) is a patient-reported ET-specific 30-item, specific quality of life scale. Items contribute to five dimensions. Physical/ADL (9 items ), Psychosocial (9 items), Communication (3 items), Hobbies/Leisure (3 items), and Work/Finances (6 items). The QUEST total and subscale scores are calculated as the sum of all applicable items divided by the number of applicable items times 100. Higher score indicates greater dissatisfaction with that domain of QOL. Maximal score 100: worse quality of life. Minimal Score 0: best quality of life. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Timepoint [13] 0 0
Baseline (Day 0), Days 7, 21 and 42

Eligibility
Key inclusion criteria
1. Clinical diagnosis of ET consistent with Movement Disorders Society Criteria, a duration of ET of at least 3 years and with onset before the age of 65
2. TETRAS upper limb score (ie, sum of bilateral upper limb items 4a, 4b, and 4c) of =10 as rated by the Investigator at Screening and Baseline OR A score of =2 on 2 or more of the following TETRAS activities of daily living (ADL) subscale items: (2) Feeding with a spoon, (3) Drinking from a glass, (5) Dressing, (6) Pouring, (9) Writing OR A score of =2 on 1 of the following TETRAS ADL subscale items: (2) Feeding with a spoon, (3) Drinking from a glass, (5) Dressing, (6) Pouring, or (9) Writing AND a score of =2 on both of the following TETRAS ADL subscale items: (10) Working and (12) Social Impact
3. If currently receiving any medication for ET, is on a stable dose of any of these medications for ET for 28 days prior to Screening and is willing to maintain stable doses throughout the trial. If receiving primidone for ET, is willing and able to discontinue 14 days prior to Day 1.
4. Body mass index (BMI) between 18 and 40 kg/m2 (inclusive).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Sporadically using a benzodiazepine, sleep medication, or anxiolytic that would confound the assessment of tremor.
2. Trauma to the nervous system within 3 months preceding the onset of tremor.
3. History of other medical, neurological or psychiatric condition that may explain or cause tremor, including but not limited to Parkinson's disease, dystonia, cerebellar disease, family history of Fragile X syndrome, traumatic brain injury, alcohol abuse or withdrawal, benzodiazepine abuse or withdrawal, multiple sclerosis, polyneuropathy, and endocrine states such as hyperthyroidism.
4. Prior magnetic resonance-guided focused ultrasound or surgical intervention for ET such as deep brain stimulation or thalamotomy.
5. Botulinum toxin injection for ET in the 6 months prior to Screening.
6. Unwilling or unable to refrain from alcohol 24 hours before and during clinical trial visits.
7. History of substance use disorder

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/03/2022
Sample size
Target
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
New South WhalesQLD,VIC
Recruitment hospital [1] 0 0
Praxis Research Site - New Lambton Heights
Recruitment hospital [2] 0 0
Praxis Research Site - Southport
Recruitment hospital [3] 0 0
Praxis Research Site - Fitzroy
Recruitment hospital [4] 0 0
Praxis Research Site - Melbourne
Recruitment hospital [5] 0 0
Praxis Research Site - Parkville
Recruitment postcode(s) [1] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Washington
Country [3] 0 0
New Zealand
State/province [3] 0 0
Auckland
Country [4] 0 0
New Zealand
State/province [4] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Praxis Precision Medicines
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
VP, Clinical Development
Address 0 0
Praxis Precision Medicines
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT05021978