Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET)

NCT06087276 | Enrolling By Invitation Phase 3 DMC FDA Drug

• 1 other identifier: PRAX-944-321
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical study is to compare ulixacaltamide and placebo treatment in essential tremor. The main question it aims to answer is: • Is ulixacaltamide a safe and efficacious treatment for patients with essential tremor? Participants will be asked to participate in one of two clinical studies where they will be treated with either ulixacaltamide or placebo for a period of up to 12 weeks. After the controlled study completion, they will be eligible to participate in a long-term, open-label safety study (LTSS) and be treated with ulixacaltamide. Participants are eligible to enroll directly into the LTSS if they previously participated in an essential tremor trial, received sponsor invitation after being deemed ineligible for the controlled study, or following enrollment closure of the controlled study.

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 (3)

• Parallel Design: Change from Baseline (CFB) to Week 8 (Day 56) on mADL11 score

  Modified Activities of Daily Living 11 (mADL11) is a composite sum of items 1 to 11 of the TETRAS-ADL subscale. 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 score is calculated as the sum of all 11 items (with scoring adjustments) and ranges from 0 to 33 where larger values represent increased direct tremor impact to activities of daily living.

  8 weeks (56 days)

• Randomized Withdrawal: The proportion of participants that maintain response, as defined by change in mADL11 score, following randomized withdrawal

  Modified Activities of Daily Living 11 (mADL11) is a composite sum of items 1 to 11 of the TETRAS-ADL subscale. 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 score is calculated as the sum of all 11 items (with scoring adjustments) and ranges from 0 to 33 where larger values represent increased direct tremor impact to activities of daily living. Change in patient response will compare the proportion of patients in the ulixacaltamide and placebo arm who maintain response based on RW baseline established at Week 8 (Day 56) following randomized withdrawal.

  12 weeks (84 days)

• Long-term Safety Study: Number of participants with Adverse Events (AE) and their severity.

  The number of participants with Adverse Events (AE) will be reported by preferred term

  Up to 3 years

Secondary Outcomes (6)

• Parallel Design: Rate of Disease improvement as Measured by mADL11

  12 weeks (84 days)

• Parallel Design: PGI-C Change at Week 8 (Day 56)

  8 weeks (56 Days)

• Parallel Design: CGI-S Change from Baseline to Week 8 (Day 56)

  8 weeks (56 Days)

• Randomized Withdrawal: Rate of Disease Improvement as Measured by Slope of mADL11 from Day 56 to Day 84

  4 weeks (28 days)

• Randomized Withdrawal: PGI-C at Day 84

  4 weeks (28 days)

Study Arms (6)

Parallel Design: ulixacaltamide arm

EXPERIMENTAL

Double-blind Part: Oral dosing, once daily in the morning with titration over 14 days to 60 mg ulixacaltamide: 7 days of 20 mg, 7 days of 40 mg, 70 days of 60 mg

Drug: 60 mg ulixacaltamide

Parallel Design: placebo arm

PLACEBO COMPARATOR

Double-blind Part: Oral dosing, once daily in the morning: 84 days of placebo

Drug: Placebo

Randomized Withdrawal

EXPERIMENTAL

Double-blind Part: Oral dosing, once daily in the morning with titration over 14 days to 60 mg ulixacaltamide: 7 days of 20 mg, 7 days of 40 mg, 42 days of 60 mg Randomized Withdrawal Part: Following double-blind part: 1:1 randomization to placebo or 60 mg ulixacaltamide for 28 days

Drug: 60 mg ulixacaltamide; Drug: Placebo

Long-term Safety Study: Essential1 rollovers

EXPERIMENTAL

Open-label Part: Oral dosing, once daily in the morning up to 3 years 60 mg ulixacaltamide

Drug: 60 mg ulixacaltamide

Long-term Safety Study: Parallel Design and Randomized Withdrawal rollovers

EXPERIMENTAL

Open-label Part for patients previously on placebo: Oral dosing, once daily in the morning with titration over 14 days to 60 mg ulixacaltamide: 7 days of 20 mg, 7 days of 40 mg, up to 3 years 60 mg ulixacaltamide Open-label Part for patients previously on 60 mg ulixacaltamide: Oral dosing, once daily in the morning up to 3 years 60 mg ulixacaltamide

Drug: 60 mg ulixacaltamide

Long-term Safety Study: Direct Enrollment to LTSS Study

EXPERIMENTAL

Oral dosing, once daily in the morning with titration over 14 days to 60 mg ulixacaltamide: 7 days of 20 mg, 7 days of 40 mg, up to 3 years 60 mg ulixacaltamide

Drug: 60 mg ulixacaltamide

Interventions

60 mg ulixacaltamide DRUG

Once daily oral treatment with titration

Long-term Safety Study: Direct Enrollment to LTSS Study; Long-term Safety Study: Essential1 rollovers; Long-term Safety Study: Parallel Design and Randomized Withdrawal rollovers; Parallel Design: ulixacaltamide arm; Randomized Withdrawal

Placebo DRUG

Once daily oral treatment

Parallel Design: placebo arm; Randomized Withdrawal

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a body mass index (BMI) at Screening of ≥18 kg/m2.
• Has a clinical diagnosis of ET confirmed during screening and characterized by postural and action tremor.
• If currently receiving medication prescribed for ET, must be on ≤1 medications, on stable dose(s) for at least 1 month prior to Screening, and willing to maintain stable dose(s) throughout the study. As needed (PRN) use of prescribed ET medicines is not allowed with the exception of propranolol PRN. Participants prescribed propranolol PRN are eligible but must discontinue the PRN dose after the first day of screening. Primidone use is not allowed within 2 weeks prior to screening and throughout duration of study.
• Women of childbearing potential must undertake pregnancy tests, with a documented negative serum pregnancy test at Screening, negative urine pregnancy tests at Baseline (Day 1) prior to administration of study drug, throughout the intervention periods (as outlined in the SoA) and at the SFU or ED Visit, as appropriate.
• Is willing and able to use contraception as defined in the protocol and ICF.
• Has been assessed as an appropriate and suitable candidate by investigator and has a neurological exam and medical record(s) consistent with ET diagnosis, as confirmed by the ERC central reviewer.

You may not qualify if:

• Neuropathy, muscle weakness, arthropathy or other musculoskeletal diagnosis of the upper extremity that impairs dexterity or function.
• Has a known hypersensitivity to any component of the formulation of ulixacaltamide.
• Is unwilling or unable to refrain from episodic use of medication(s)/substance(s) that might interfere with the evaluation of tremor during the study.
• Is sporadically using a benzodiazepine, sleep medication or anxiolytic (as further defined in the protocol), that in the judgement of the investigator or sponsor would confound the assessment of tremor.
• Has trauma to the nervous system within 3 months preceding the onset of tremor.
• Has a history of unilateral tremor or clinical evidence of another 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, stroke with neurologic sequelae, intention tremor (IT) caused by etiology other than ET, 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 (diabetic neuropathy allowed if disease does not affect gait or balance and does not involve upper extremity), and endocrine states such as uncontrolled or inadequately treated hypothyroidism, food, or supplement induced movement disorders (e.g., tremor related to beta agonists or caffeine), or other medical, neurological, or psychiatric conditions that may explain or cause tremor.
• Has had prior magnetic resonance-guided focused ultrasound or surgical intervention for ET such as a deep brain stimulator (DBS) or lesion therapy such as thalamotomy.
• Has had botulinum toxin injection for ET in the 6 months prior to Screening or throughout the study.
• Is using the Cala trio health device for ET in 14 days prior to Screening or throughout the study.
• Is unwilling or unable to refrain from drinking alcohol 24 hours before and during clinical study assessments, or regular use of alcohol that would preclude abstinence from alcohol for this time period around visits.
• Has a history of substance use disorder consistent with Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision (DSM-5-TR) criteria. Participants with a previous diagnosis of substance use disorder who have been in remission for at least 2 years can participate in the study.
• Is currently pregnant or breastfeeding or is planning to become pregnant during the clinical trial or within 31 days of the last study drug dose.
• Is currently taking a prescription or non-prescription product(s) and food known to be moderate or strong inhibitors or strong inducers (moderate inducers are not prohibited) of cytochrome P450 (CYP3A4), which cannot be discontinued at least 5 half-lives or 14 days prior (whichever is the longer period of time) to Baseline and withheld throughout the clinical study.
• Has received any experimental or investigational drug, device, or other therapy within 30 days or 5 half-lives (whichever is longer) prior to Screening.
• Has any of the following abnormal test results at Screening: a serum total bilirubin value \>1.5×upper limit of normal (ULN); a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \>2×ULN. As an exception, participants that present with elevated bilirubin in the absence of elevations in ALT or AST that fits the pattern of Gilbert's syndrome may be enrolled after discussion with the medical monitor and/or sponsor designee if their conjugated bilirubin is below the ULN.

Sponsors & Collaborators

• Praxis Precision Medicines: lead

Study Sites (1)

United BioSource LLC

Morgantown, West Virginia, 26508, United States

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 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Blinded randomization into either the Parallel Design or Randomized Withdrawal studies
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * Parallel Design: A 12-week parallel design (PD) randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of ulixacaltamide compared with placebo. * Randomized Withdrawal: A 12-week randomized withdrawal (RW), double-blind, placebo-controlled study to evaluate the efficacy, maintenance of response, and durability of effect in participants who respond to ulixacaltamide and safety. * Long-term Safety Study: A LTSS study to evaluate the long-term safety of ulixacaltamide for up to approximately 3 years. The first 2 weeks of the LTSS will be double-blind.

Study Record Dates

• First Submitted: October 12, 2023
• First Posted: October 17, 2023
• Study Start: November 2, 2023
• Primary Completion: September 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

US (1)