Clinical trial NCT05021991: A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Range Finding Clinical Trial to Evaluate the Efficacy, Tolerability, and Safety of PRAX-944 in the Treatment of Adults With Essential Tremor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Essential Tremor
Keywords: Movement Disorder
Benign Essential Tremor
Familial Tremor
Hereditary Essential Tremor
Movement Disorder Agents
Calcium Channels, T-type
Lead sponsor: Praxis Precision Medicines
Sponsor class: INDUSTRY
First posted: 2021-08-26
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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. Participant has moderate to severe functional impairment due to tremor as determined by the TETRAS and CGI-S.
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 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.

Primary outcomes:
measure: Change from baseline to Day 56 on the modified ADL
timeFrame: 56 days
Secondary outcomes:
measure: Change from baseline to Day 56 on the Clinical Global Impression-Severity (CGI-S)
timeFrame: 56 days
measure: Clinical Global Impression-Improvement (CGI-I) score at Day 56
timeFrame: 56 days
measure: Change from baseline to Day 56 on the TETRAS-ADL score
timeFrame: 56 days
measure: Change from baseline to Day 56 on the TETRAS-Performance Subscale (PS) total score
timeFrame: 56 days
measure: Change from baseline to Day 56 on the TETRAS-upper limb (UL) score (TETRAS-PS item 4)
timeFrame: 56 days
measure: Change from baseline to Day 56 on the TETRAS-combined upper limb (CUL) score (TETRAS-PS sum of items 4, 6, 7, and 8)
timeFrame: 56 days
measure: Patient Global Impression-Change (PGI-C) score at Day 56
timeFrame: 56 days
measure: Change from baseline to Days 14, 28, and 42 on the modified ADL
timeFrame: Up to 42 days
measure: Change from baseline to Days 14, 28, and 42 on the CGI-S
timeFrame: Up to 42 days
measure: Change from baseline to Days 14, 28, and 42 on the TETRAS-ADL total score
timeFrame: Up to 42 days
measure: Change from baseline to Days 14, 28, and 42 on the TETRAS-UL score
timeFrame: Up to 42 days
measure: Change from baseline to Days 14, 28, and 42 on the TETRAS-CUL score
timeFrame: Up to 42 days
measure: CGI-I scores at Days 14, 28, and 42
timeFrame: Up to 42 days
measure: PGI-C scores at Days 14, 28, and 42
timeFrame: Up to 42 days
measure: Change from baseline to Day 42 on the TETRAS-PS total score
timeFrame: 42 days
measure: Number of participants with Adverse Events (AE)
timeFrame: Up to 56 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Praxis Research Site
state: Alabama
city: Little Rock
country: United States
facility: Praxis Research Site
state: Arkansas
city: San Diego
country: United States
facility: Praxis Research Site
state: California
city: Santa Monica
country: United States
facility: Praxis Research Site
state: California
city: Torrance
country: United States
facility: Praxis Research Site
state: California
city: Aurora
country: United States
facility: Praxis Research Site
state: Colorado
city: Boca Raton
country: United States
facility: Praxis Research Site
state: Florida
city: Gainesville
country: United States
facility: Praxis Research Site
state: Florida
city: Jacksonville
country: United States
facility: Praxis Research Site
state: Florida
city: Port Charlotte
country: United States
facility: Praxis Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Praxis Research Site
state: Florida
city: Tampa
country: United States
facility: Praxis Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Praxis Research Site
state: Florida
city: Chicago
country: United States
facility: Praxis Research Site
state: Illinois
city: Kansas City
country: United States
facility: Praxis Research Site
state: Kansas
city: Louisville
country: United States
facility: Praxis Research Site
state: Kentucky
city: Rockville
country: United States
facility: Praxis Research Site
state: Maryland
city: Boston
country: United States
facility: Praxis Research Site
state: Massachusetts
city: Burlington
country: United States
facility: Praxis Research Site
state: Massachusetts
city: Farmington Hills
country: United States
facility: Praxis Research Site
state: Michigan
city: Golden Valley
country: United States
facility: Praxis Research Site
state: Minnesota
city: Las Vegas
country: United States
facility: Praxis Research Site
state: Nevada
city: New York
country: United States
facility: Praxis Research Site
state: New York
city: New York
country: United States
facility: Praxis Research Site
state: New York
city: Cincinnati
country: United States
facility: Praxis Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Praxis Research Site
state: Pennsylvania
city: Georgetown
country: United States
facility: Praxis Research Site
state: Texas
city: Houston
country: United States
facility: Praxis Research Site
state: Texas
city: Round Rock
country: United States
facility: Praxis Research Site
state: Texas
city: Burlington
country: United States
facility: Praxis Research Site
state: Vermont
city: Alexandria
country: United States
facility: Praxis Research Site
state: Virginia
city: Virginia Beach
country: United States
facility: Praxis Research Site
state: Virginia
city: Kirkland
country: United States
facility: Praxis Research Site
state: Washington
city: Spokane
country: United States
facility: Praxis Research Site
state: Washington
city: Milwaukee
country: United States
facility: Praxis Research Site
state: Wisconsin
city: Vancouver
country: Canada
facility: Praxis Research Site
state: British Columbia
city: Halifax
country: Canada
facility: Praxis Research Site
state: Nova Scotia
city: Toronto
country: Canada
facility: Praxis Research Site
state: Ontario
city: Montréal
country: Canada
facility: Praxis Research Site
state: Quebec
Study officials:
affiliation: Praxis Precision Medicines
name: Director, Clinical Development
role: STUDY_DIRECTOR
References: