A Clinical Trial of 3 Doses of PRAX-944 in Participants With Essential Tremor

• ClinicalTrials.gov Identifier: NCT05021991
• Recruitment Status: Recruiting
• First Posted: August 26, 2021
• Last Update Posted: June 7, 2022
• Sponsor: Praxis Precision Medicines
• Information provided by (Responsible Party): Praxis Precision Medicines

Study Description

Brief Summary:

This is a randomized, double-blind, placebo-controlled clinical trial to evaluate the tolerability, safety, and efficacy of 20, 60, and 100 mg oral PRAX-944 compared to placebo in the treatment of adults with essential tremor. Blood levels of PRAX-944 will also be measured throughout the trial.

Condition or disease	Intervention/treatment	Phase
Essential Tremor	Drug: 100 mg PRAX-944; Drug: 60 mg PRAX-944; Drug: 20 mg PRAX-944; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Range Finding Clinical Trial to Evaluate the Tolerability, Safety, and Efficacy of PRAX-944 in the Treatment of Adults With Essential Tremor
• Actual Study Start Date: October 14, 2021
• Estimated Primary Completion Date: September 2022
• Estimated Study Completion Date: October 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: PRAX-944 (100 mg); Once daily, oral dosing with titration to 100 mg: 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	Drug: 100 mg PRAX-944; Once daily oral treatment with titration
Experimental: PRAX-944 (60 mg); Once daily, oral dosing with titration to 60 mg: 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	Drug: 60 mg PRAX-944; Once daily oral treatment with titration; Drug: Placebo; Once daily oral treatment
Experimental: PRAX-944 (20 mg); Once daily, oral dosing with titration to 20 mg: 7 days of 5 mg, 7 days of 10 mg, 42 days of 20 mg	Drug: 20 mg PRAX-944; Once daily oral treatment with titration; Drug: Placebo; Once daily oral treatment
Placebo Comparator: Placebo; Once daily, oral dosing: 56 days of placebo	Drug: Placebo; Once daily oral treatment

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of Adverse Events (AE) [ Time Frame: 56 days ]
   An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study drug, whether or not considered related to the study drug.

Secondary Outcome Measures :

1. Change from baseline to Day 56 on the Essential Tremor Rating Assessment Scale (TETRAS) combined upper limb (CUL) score [ Time Frame: 56 days ]
   The TETRAS is an essential tremor and activities of daily living rating scale. The full scale has 2 sections, the TETRAS Performance subscale (PS) and the TETRAS ADL subscale. The TETRAS PS consists of 9 items covering different body regions. TETRAS CUL aggregates the upper limb items from the TETRAS PS including Items 4, 6, 7 and 8. The total score for the TETRAS CUL ranges from 0 to 44 with higher scores indicating greater tremor severity.
2. Change from baseline to Day 56 on the TETRAS Activities of Daily Living (ADL) score [ Time Frame: 56 days ]
   The TETRAS ADL subscale consists of 12 items measuring the impact of essential tremor on typical daily activities. These 12 items are rated on a 5-point scale (ranging from 0 to 4). The total score of the 12 items ranges from 0 to 48 with higher scores indicating greater tremor severity.
3. Change from baseline to Day 56 on the TETRAS Modified Total Score [ Time Frame: 56 days ]
   The TETRAS Modified Total Score is comprised of TETRAS ADL and TETRAS PS spirography and handwriting scores.

Other Outcome Measures:

1. Incidence of AEs by preferred term [ Time Frame: 56 days ]
   The incidence of AEs will be reported by preferred term, including any terms related to clinically significant changes in body temperature, pulse rate, respiratory rate, blood pressure (systolic and diastolic), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), and electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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.
2. TETRAS upper limb score (ie, sum of bilateral upper limb items 4a, 4b, and 4c) of ≥10 as rated by the Investigator.
3. 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.
4. Body mass index (BMI) between 18 and 40 kg/m2 (inclusive).

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 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
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 Baseline.
6. Cala trio health device for ET in the 14 days prior to Baseline and throughout the study.
7. History of substance use disorder

Contacts and Locations

Contacts

Contact: Chief Medical Officer, Praxis Precision Medicines; 617-300-8460; clinicaltrials@praxismedicines.com

Locations

United States, Alabama

Praxis Research Site; Not yet recruiting

Birmingham, Alabama, United States, 35294

United States, Arkansas

Praxis Research Site; Recruiting

Little Rock, Arkansas, United States, 72205

United States, California

Praxis Research Site; Recruiting

San Diego, California, United States, 92103

Praxis Research Site; Recruiting

Santa Monica, California, United States, 90404

Praxis Research Site; Recruiting

Torrance, California, United States, 90503

United States, Colorado

Praxis Research Site; Not yet recruiting

Aurora, Colorado, United States, 80045

United States, Florida

Praxis Research Site; Recruiting

Boca Raton, Florida, United States, 33486

Praxis Research Site; Not yet recruiting

Gainesville, Florida, United States, 32608

Praxis Research Site; Recruiting

Jacksonville, Florida, United States, 32209

Praxis Research Site; Recruiting

Port Charlotte, Florida, United States, 33980

Praxis Research Site; Recruiting

Saint Petersburg, Florida, United States, 33713

Praxis Research Site; Recruiting

Tampa, Florida, United States, 33612

Praxis Research Site; Completed

West Palm Beach, Florida, United States, 33407

United States, Georgia

Praxis Research Site; Not yet recruiting

Atlanta, Georgia, United States, 30329

United States, Illinois

Praxis Research Site; Not yet recruiting

Chicago, Illinois, United States, 60612

United States, Kansas

Praxis Research Site; Recruiting

Kansas City, Kansas, United States, 66160

United States, Kentucky

Praxis Research Site; Not yet recruiting

Louisville, Kentucky, United States, 40202

United States, Maryland

Praxis Research Site; Not yet recruiting

Rockville, Maryland, United States, 20852

United States, Massachusetts

Praxis Research Site; Recruiting

Boston, Massachusetts, United States, 02118

Praxis Research Site; Not yet recruiting

Boston, Massachusetts, United States, 02135

Praxis Research Site; Not yet recruiting

Burlington, Massachusetts, United States, 01805

United States, Michigan

Praxis Research Site; Recruiting

Farmington Hills, Michigan, United States, 48334

United States, Minnesota

Praxis Research Site; Recruiting

Golden Valley, Minnesota, United States, 55427

United States, Nevada

Praxis Research Site; Not yet recruiting

Las Vegas, Nevada, United States, 89106

United States, New York

Praxis Research Site; Recruiting

New York, New York, United States, 10029

Praxis Research Site; Not yet recruiting

New York, New York, United States, 10032

United States, Ohio

Praxis Research Site; Recruiting

Cincinnati, Ohio, United States, 45212

Praxis Research Site; Not yet recruiting

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

Praxis Research Site; Recruiting

Philadelphia, Pennsylvania, United States, 19107

United States, Tennessee

Praxis Research Site; Not yet recruiting

Nashville, Tennessee, United States, 37232

United States, Texas

Praxis Research Site; Recruiting

Georgetown, Texas, United States, 78628

Praxis Research Site; Not yet recruiting

Houston, Texas, United States, 77030-4202

Praxis Research Site; Not yet recruiting

Houston, Texas, United States, 77030

Praxis Research Site; Recruiting

Round Rock, Texas, United States, 78681

United States, Vermont

Praxis Research Site; Active, not recruiting

Burlington, Vermont, United States, 05401

United States, Virginia

Praxis Research Site; Recruiting

Alexandria, Virginia, United States, 22311

Praxis Research Site; Recruiting

Virginia Beach, Virginia, United States, 23456

United States, Washington

Praxis Research Site; Recruiting

Kirkland, Washington, United States, 98034

Praxis Research Site; Recruiting

Spokane, Washington, United States, 99202

United States, Wisconsin

Praxis Research Site; Recruiting

Milwaukee, Wisconsin, United States, 53226

Canada, British Columbia

Praxis Research Site; Recruiting

Vancouver, British Columbia, Canada, V6T 2B5

Canada, Nova Scotia

Praxis Research Site; Active, not recruiting

Halifax, Nova Scotia, Canada, B3S 1N2

Canada, Ontario

Praxis Research Site; Not yet recruiting

Toronto, Ontario, Canada, M5T 2S8

Canada, Quebec

Praxis Research Site; Not yet recruiting

Montréal, Quebec, Canada, H3A 2B4

Sponsors and Collaborators

Praxis Precision Medicines

Investigators

• Study Director: VP, Clinical Development; Praxis Precision Medicines

More Information

• Responsible Party: Praxis Precision Medicines
• ClinicalTrials.gov Identifier: NCT05021991
• Other Study ID Numbers: PRAX-944-222
• First Posted: August 26, 2021
• Last Update Posted: June 7, 2022
• Last Verified: June 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Praxis Precision Medicines:

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

Additional relevant MeSH terms:

Tremor; Essential Tremor; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Movement Disorders; Central Nervous System Diseases; Pramoxine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents