A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor

NCT05021991 | Completed Phase 2 FDA Drug

• 1 other identifier: PRAX-944-222
• Study Type: interventional
• Target: 133
• Locations: 2 countries
• Sites: 39

Brief Summary

This multi-center, randomized, double-blinded, placebo-controlled, dose-range-finding clinical trial (with an optional Extension comprised of an Extension Double-blind (DB) Lead in Period followed by an Extension Open-label (OL) Period) that will assess the efficacy, safety, and tolerability of PRAX 944 in participants aged 18 years or older who have a diagnosis of Essential Tremor (ET) and have had symptoms for at least 3 years.

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 (1)

• Change from baseline to Day 56 on the modified ADL

  The modified ADL is a composite sum of items 1 to 11 of the TETRAS-ADL subscale and items 6 and 7 on the TETRAS-PS. The impact to each function is rated on a 5-point Likert scale from 0 to 4. Before calculating the total score, a scoring adjustment is applied to each item score. The modified ADL score is calculated as the sum of all 13 items (with scoring adjustments) and ranges from 0 to 42 where larger values represent increased direct tremor impact to activities of daily living.

  56 days

Secondary Outcomes (16)

• Change from baseline to Day 56 on the Clinical Global Impression-Severity (CGI-S)

  56 days

• Clinical Global Impression-Improvement (CGI-I) score at Day 56

  56 days

• Change from baseline to Day 56 on the TETRAS-ADL score

  56 days

• Change from baseline to Day 56 on the TETRAS-Performance Subscale (PS) total score

  56 days

• Change from baseline to Day 56 on the TETRAS-upper limb (UL) score (TETRAS-PS item 4)

  56 days

Study Arms (3)

Regimen 1

EXPERIMENTAL

Double-blind Part: Oral dosing, once daily in the morning with titration over 56 days to 100 mg PRAX-944: 7 days of 5 mg, 7 days of 10 mg, 7 days of 20 mg, 7 days of 40 mg, 7 days of 60 mg, 7 days of 80 mg, 14 days of 100 mg Extension Part: Double-blind Lead-in: Oral dosing, once daily in the morning over 43 days: 100 mg PRAX-944 Extension Part: Open-label Flexible PRAX-944 Dosing: Oral dosing, once daily in the morning of 20 mg to 100 mg PRAX-944 for 469 days Crossover Part: Following double-blind lead-in/open-label: 1:1 randomization to placebo or stable dose of PRAX-944 for 21 days followed by cross-over to either placebo or PRAX-944 oral dosing, once daily in the morning with titration over 7 days (3 days at 20 mg, 4 days at 40 mg) to 60 mg (14 days) before returning to open-label part.

Drug: 100 mg PRAX-944; Drug: 60 mg PRAX-944; Drug: Placebo; Drug: Flexibly dosed 20 mg to 100 mg PRAX-944

Regimen 2

EXPERIMENTAL

Double-blind Part: Oral dosing, once daily in the morning with titration over 56 days to 60 mg PRAX-944: 7 days of 5 mg, 7 days of 10 mg, 7 days of 20 mg, 7 days of 40 mg, 28 days of 60 mg Extension Part: Double-blind Lead-in: Oral dosing, once daily in the morning with titration over 43 days to 100 mg PRAX-944: 7 days of 80 mg, 36 days of 100 mg Extension Part: Open-label Flexible PRAX-944 Dosing: Oral dosing, once daily in the morning of 20 mg to 100 mg PRAX-944 for 469 days Crossover Part: Following double-blind lead-in/open-label: 1:1 randomization to placebo or stable dose of PRAX-944 for 21 days followed by cross-over to either placebo or PRAX-944 oral dosing, once daily in the morning with titration over 7 days (3 days at 20 mg, 4 days at 40 mg) to 60 mg (14 days) before returning to open-label part.

Drug: 100 mg PRAX-944; Drug: 60 mg PRAX-944; Drug: Placebo; Drug: Flexibly dosed 20 mg to 100 mg PRAX-944

Regimen 3

PLACEBO COMPARATOR

Double-blind Part: Oral dosing, once daily in the morning: 56 days of placebo Extension Part: Double-blind Lead-in: Oral dosing, once daily in the morning with titration over 43 days to 100 mg PRAX-944: 7 days of 5 mg, 7 days of 10 mg, 7 days of 20 mg, 7 days of 40 mg, 7 days of 60 mg, 7 days of 80 mg, 14 days of 100 mg Extension Part: Open-label Flexible PRAX-944 Dosing: Oral dosing, once daily in the morning of 20 mg to 100 mg PRAX-944 for 469 days Crossover Part: Following double-blind lead-in/open-label: 1:1 randomization to placebo or stable dose of PRAX-944 for 21 days followed by cross-over to either placebo or PRAX-944 oral dosing, once daily in the morning with titration over 7 days (3 days at 20 mg, 4 days at 40 mg) to 60 mg (14 days) before returning to open-label part.

Drug: 100 mg PRAX-944; Drug: 60 mg PRAX-944; Drug: Placebo; Drug: Flexibly dosed 20 mg to 100 mg PRAX-944

Interventions

100 mg PRAX-944 DRUG

Once daily oral treatment with titration

Regimen 1; Regimen 2; Regimen 3

60 mg PRAX-944 DRUG

Once daily oral treatment with titration

Regimen 1; Regimen 2; Regimen 3

Placebo DRUG

Once daily oral treatment

Regimen 1; Regimen 2; Regimen 3

Flexibly dosed 20 mg to 100 mg PRAX-944 DRUG

Once daily oral treatment

Regimen 1; Regimen 2; Regimen 3

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, including: (a) tremor syndrome of bilateral upper limb action tremor, (b) at least 3 years in duration, (c) with or without tremor in other locations (eg, head, voice, or lower limbs), (d) If the symptoms and signs are judged by the investigator to be due to the diagnosis of ET, it is acceptable for them to also have one or more of the following ET plus signs: (i) mild dystonic posturing, (ii) mild rest tremor in the setting of advanced ET and in the absence of other features of Parkinsonism, (iii) intention tremor, (iv) mild increase in tandem gait difficulty.
• Participant has moderate to severe functional impairment due to tremor as determined by the TETRAS and CGI-S.
• If currently receiving any medication for ET, is on a stable dose of any of these medications for ET for 1 month 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 or clinical evidence of other medical, neurological, or psychiatric condition that may explain or cause tremor, including but not limited to Parkinson's disease, Huntington's disease, Alzheimer's disease, cerebellar disease (including spinocerebellar ataxias), primary dystonia, Fragile X Tremor/Ataxia syndrome or family history of Fragile X syndrome, traumatic brain injury, psychogenic tremor, alcohol or benzodiazepine abuse or withdrawal, multiple sclerosis, polyneuropathy, and endocrine states such as hyperthyroidism or unstable treatment of hypothyroidism or medication, food, or supplement induced movement disorders (eg, tremor related to beta agonists or caffeine), or other medical, neurological, or psychiatric conditions that may explain or cause tremor
• 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 Baseline.
• Cala trio health device for ET in the 14 days prior to Baseline and throughout the study.
• History of substance use disorder consistent with Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Participants with a previous diagnosis of substance use disorder who have been in remission for at least 2 years can participate in the trial.

Sponsors & Collaborators

• Praxis Precision Medicines: lead

Study Sites (39)

Praxis Research Site

Birmingham, Alabama, 35294, United States

Location

Praxis Research Site

Little Rock, Arkansas, 72205, United States

Location

Praxis Research Site

San Diego, California, 92103, United States

Location

Praxis Research Site

Santa Monica, California, 90404, United States

Location

Praxis Research Site

Torrance, California, 90503, United States

Location

Praxis Research Site

Aurora, Colorado, 80045, United States

Location

Praxis Research Site

Boca Raton, Florida, 33486, United States

Location

Praxis Research Site

Gainesville, Florida, 32608, United States

Location

Praxis Research Site

Jacksonville, Florida, 32209, United States

Location

Praxis Research Site

Port Charlotte, Florida, 33980, United States

Location

Praxis Research Site

St. Petersburg, Florida, 33713, United States

Location

Praxis Research Site

Tampa, Florida, 33612, United States

Location

Praxis Research Site

West Palm Beach, Florida, 33407, United States

Location

Praxis Research Site

Chicago, Illinois, 60612, United States

Location

Praxis Research Site

Kansas City, Kansas, 66160, United States

Location

Praxis Research Site

Louisville, Kentucky, 40202, United States

Location

Praxis Research Site

Rockville, Maryland, 20852, United States

Location

Praxis Research Site

Boston, Massachusetts, 02118, United States

Location

Praxis Research Site

Burlington, Massachusetts, 01805, United States

Location

Praxis Research Site

Farmington Hills, Michigan, 48334, United States

Location

Praxis Research Site

Golden Valley, Minnesota, 55427, United States

Location

Praxis Research Site

Las Vegas, Nevada, 89106, United States

Location

Praxis Research Site

New York, New York, 10029, United States

Location

Praxis Research Site

New York, New York, 10032, United States

Location

Praxis Research Site

Cincinnati, Ohio, 45212, United States

Location

Praxis Research Site

Philadelphia, Pennsylvania, 19107, United States

Location

Praxis Research Site

Georgetown, Texas, 78628, United States

Location

Praxis Research Site

Houston, Texas, 77030, United States

Location

Praxis Research Site

Round Rock, Texas, 78681, United States

Location

Praxis Research Site

Burlington, Vermont, 05401, United States

Location

Praxis Research Site

Alexandria, Virginia, 22311, United States

Location

Praxis Research Site

Virginia Beach, Virginia, 23456, United States

Location

Praxis Research Site

Kirkland, Washington, 98034, United States

Location

Praxis Research Site

Spokane, Washington, 99202, United States

Location

Praxis Research Site

Milwaukee, Wisconsin, 53226, United States

Location

Praxis Research Site

Vancouver, British Columbia, V6T 2B5, Canada

Location

Praxis Research Site

Halifax, Nova Scotia, B3S 1N2, Canada

Location

Praxis Research Site

Toronto, Ontario, M5T 2S8, Canada

Location

Praxis Research Site

Montreal, Quebec, H3A 2B4, Canada

Location

MeSH Terms

Conditions

Essential Tremor; Movement Disorders

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Director, Clinical Development

  Praxis Precision Medicines

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 26, 2021
• Study Start: October 14, 2021
• Primary Completion: February 9, 2023
• Study Completion: February 29, 2024
• Last Updated: March 13, 2024

Record last verified: 2024-03

Locations

US (35); CA (4)