A Clinical Trial of PRAX-944 in Participants With Essential Tremor

NCT05021978 | Completed Phase 2 Results FDA Drug

• 1 other identifier: PRAX-944-221
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 9

Brief Summary

This is a 2-part clinical trial to evaluate the efficacy, safety, and tolerability of 40 and 120 mg oral PRAX-944 compared to placebo in the treatment of adults with essential tremor. Part A is designed to study the dose titration from 20 to 40 mg every morning (QAM) (ie, 2 weeks with 7 days at each dose level). Part B is designed to study the dose titration from 20 to up to 120 mg QAM with at least 14 days of dosing at the highest tolerated dose for each participant. Blood levels of PRAX-944 will also be measured throughout the trial and pharmacokinetics will be evaluated.

Conditions

Essential Tremor

Keywords

Movement Disorder; Benign Essential Tremor; Familial Tremor; Hereditary Essential Tremor; Movement Disorder Agents; Calcium Channels, T-type

Outcome Measures

Primary Outcomes (4)

• Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score

  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.

  Baseline (Day 0), Days 7 and 14

• Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation

  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.

  Up to Day 70

• Part B: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters

  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.

  Up to Day 70

• Part B: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)

  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).

  Up to Day 70

Secondary Outcomes (13)

• Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale

  Baseline (Day 0), Days 7 and 14

• Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry

  Baseline (Day 0), Days 7 and 14

• Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting)

  Baseline (Day 0), Days 7 and 14

• Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation

  Up to Day 21

• Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters

  Up to Day 21

Study Arms (3)

Part A: Open-label 20 and 40 mg PRAX-944

EXPERIMENTAL

Once daily, oral dosing with 7 days of 20 mg and 7 days of 40 mg

Drug: Part A: 20 and 40 mg PRAX-944

Part B: Open-label titration PRAX-944 (120 mg) followed by blinded PRAX-944

EXPERIMENTAL

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

Drug: Part B: 120 mg PRAX-944

Part B: Open-label titration PRAX-944 (120 mg) followed by blinded placebo

ACTIVE COMPARATOR

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

Drug: Part B: 120 mg PRAX-944 and Placebo

Interventions

Part A: 20 and 40 mg PRAX-944 DRUG

Once daily oral treatment

Part A: Open-label 20 and 40 mg PRAX-944

Part B: 120 mg PRAX-944 DRUG

Once daily oral treatment with titration

Part B: Open-label titration PRAX-944 (120 mg) followed by blinded PRAX-944

Part B: 120 mg PRAX-944 and Placebo DRUG

Once daily oral treatment with titration followed by placebo

Part B: Open-label titration PRAX-944 (120 mg) followed by blinded placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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.
• Body mass index (BMI) between 18 and 40 kg/m2 (inclusive).

You may not qualify if:

• Sporadically using a benzodiazepine, sleep medication, or anxiolytic that would confound the assessment of tremor.
• Trauma to the nervous system within 3 months preceding the onset of tremor.
• 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.
• Prior magnetic resonance-guided focused ultrasound or surgical intervention for ET such as deep brain stimulation or thalamotomy.
• Botulinum toxin injection for ET in the 6 months prior to Screening.
• Unwilling or unable to refrain from alcohol 24 hours before and during clinical trial visits.
• History of substance use disorder

Sponsors & Collaborators

• Praxis Precision Medicines: lead

Study Sites (9)

Praxis Research Site

Port Charlotte, Florida, 33980, United States

Location

Praxis Research Site

Spokane, Washington, 99202, United States

Location

Praxis Research Site

New Lambton Heights, New South Whales, 2305, Australia

Location

Praxis Research Site

Southport, Queensland, 4215, Australia

Location

Praxis Research Site

Fitzroy, Victoria, 3065, Australia

Location

Praxis Research Site

Melbourne, Victoria, 3004, Australia

Location

Praxis Research Site

Parkville, Victoria, 3050, Australia

Location

Praxis Research Site

Grafton, Auckland, 1023, New Zealand

Location

Praxis Research Site

Christchurch, 8011, New Zealand

Location

MeSH Terms

Conditions

Essential Tremor; Movement Disorders

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Due to repeated mistakes during the eligibility review process, a Corrective and Preventative Actions (CAPA) report was issued and enrollment at one site was suspended.

Results Point of Contact

• Title: Charmaine Manilay
• Organization: Praxis Precision Medicines

cmanilay@praxismedicines.com

2243996121

Study Officials

• VP, Clinical Development

  Praxis Precision Medicines

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part A: Open label Part B: Open label titration followed by quadruple-blind, randomized withdrawal
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: Single group Part B: Parallel group, randomized withdrawal

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 26, 2021
• Study Start: March 3, 2020
• Primary Completion: March 24, 2022
• Study Completion: March 24, 2022
• Last Updated: March 1, 2024
• Results First Posted: March 1, 2024

Record last verified: 2024-01

Locations

US (2); AU (5); NZ (2)