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

Sponsor

Praxis Precision Medicines (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05021991

Collaborator

(none)

131

Enrollment

Locations

Arms

11.6

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Essential Tremor	Drug: 100 mg PRAX-944 Drug: 60 mg PRAX-944 Drug: Placebo Drug: Flexibly dosed 20 mg to 100 mg PRAX-944	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

131 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 Efficacy, Tolerability, and Safety of PRAX-944 in the Treatment of Adults With Essential Tremor

Actual Study Start Date :

Oct 14, 2021

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regimen 1 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 90 days	Drug: 100 mg PRAX-944 Once daily oral treatment with titration Drug: Flexibly dosed 20 mg to 100 mg PRAX-944 Once daily oral treatment
Experimental: Regimen 2 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 90 days	Drug: 100 mg PRAX-944 Once daily oral treatment with titration Drug: 60 mg PRAX-944 Once daily oral treatment with titration Drug: Flexibly dosed 20 mg to 100 mg PRAX-944 Once daily oral treatment
Placebo Comparator: Regimen 3 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 90 days	Drug: 100 mg PRAX-944 Once daily oral treatment with titration Drug: Placebo Once daily oral treatment Drug: Flexibly dosed 20 mg to 100 mg PRAX-944 Once daily oral treatment

Arm

Intervention/Treatment

Experimental: Regimen 1

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 90 days

Drug: 100 mg PRAX-944

Once daily oral treatment with titration

Drug: Flexibly dosed 20 mg to 100 mg PRAX-944

Once daily oral treatment

Experimental: Regimen 2

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 90 days

Drug: 100 mg PRAX-944

Once daily oral treatment with titration

Drug: 60 mg PRAX-944

Once daily oral treatment with titration

Drug: Flexibly dosed 20 mg to 100 mg PRAX-944

Once daily oral treatment

Placebo Comparator: Regimen 3

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 90 days

Drug: 100 mg PRAX-944

Once daily oral treatment with titration

Drug: Placebo

Once daily oral treatment

Drug: Flexibly dosed 20 mg to 100 mg PRAX-944

Once daily oral treatment

Outcome Measures

Primary Outcome Measures

Change from baseline to Day 56 on the modified ADL [56 days]
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.

Secondary Outcome Measures

Change from baseline to Day 56 on the Clinical Global Impression-Severity (CGI-S) [56 days]
The CGI-S assesses the clinician's impression of the participant's current illness state. The clinician should use his/her total clinical experience with this patient population and rate the current severity of the participant's ET on a 7-point scale from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Clinical Global Impression-Improvement (CGI-I) score at Day 56 [56 days]
The CGI-I assesses the participant's improvement (or worsening). The clinician is required to assess the participant's condition relative to pre-treatment on a 7-point scale from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement/worsening is drug-related or not.
Change from baseline to Day 56 on the TETRAS-ADL score [56 days]
The TETRAS-ADL subscale is a 12-item assessment of typical daily activities that are impacted by tremor. Activities are assessed in the following functional domains: speaking, feeding, drinking, personal hygiene, dressing, writing, and social activity. The impact to each function is rated on a 5-point Likert scale from 0 to 4. The ADL subscale score is calculated as the sum of all 12 items and ranges from 0 to 48 where larger values represent increased direct tremor impact to activities of daily living.
Change from baseline to Day 56 on the TETRAS-Performance Subscale (PS) total score [56 days]
There are 9 items covering different body regions in the Performance Subscale. Each Performance Subscale item is rated on a scale of 0 to 4, with higher scores indicating higher tremor severity. Item 4 of the Performance Subscale is the upper limb item. It is comprised of 6 sub-items (4a, 4b, and 4c assessed for both the right and left upper limbs). The Performance subscale score is calculated as the sum of all 9 items and ranges from 0 to 64 where larger values represent higher tremor severity.
Change from baseline to Day 56 on the TETRAS-upper limb (UL) score (TETRAS-PS item 4) [56 days]
Item 4 of the Performance subscale is the upper limb item. It is comprised of 6 sub-items (4a, 4b, and 4c assessed for both the right and left upper limbs). Each sub-item is rated on a scale from 0 to 4, with higher scores indicating higher tremor amplitude of the upper limb. The upper limb total score is the sum of these 6 sub-items and ranges from 0 to 24 where larger values represent higher tremor severity.
Change from baseline to Day 56 on the TETRAS-combined upper limb (CUL) score (TETRAS-PS sum of items 4, 6, 7, and 8) [56 days]
The combined upper limb score is the sum of the 6 sub-item scores of the upper limb item and the handwriting and spirals scores. The combined upper limb score ranges from 0 to 32 where larger values represent higher tremor severity.
Patient Global Impression-Change (PGI-C) score at Day 56 [56 days]
The PGI-C assesses the participant's change in condition. The participant is required to assess their condition relative to Baseline (Pre-dose on Day 1) on a 7-point scale from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the participant believes the change is drug-related or not.
Change from baseline to Days 14, 28, and 42 on the modified ADL [Up to 42 days]
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.
Change from baseline to Days 14, 28, and 42 on the CGI-S [Up to 42 days]
The CGI-S assesses the clinician's impression of the participant's current illness state. The clinician should use his/her total clinical experience with this patient population and rate the current severity of the participant's ET on a 7-point scale from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
Change from baseline to Days 14, 28, and 42 on the TETRAS-ADL total score [Up to 42 days]
The TETRAS-ADL subscale is a 12-item assessment of typical daily activities that are impacted by tremor. Activities are assessed in the following functional domains: speaking, feeding, drinking, personal hygiene, dressing, writing, and social activity. The impact to each function is rated on a 5-point Likert scale from 0 to 4. The ADL subscale score is calculated as the sum of all 12 items and ranges from 0 to 48 where larger values represent increased direct tremor impact to activities of daily living.
Change from baseline to Days 14, 28, and 42 on the TETRAS-UL score [Up to 42 days]
Item 4 of the Performance subscale is the upper limb item. It is comprised of 6 sub-items (4a, 4b, and 4c assessed for both the right and left upper limbs). Each sub-item is rated on a scale from 0 to 4, with higher scores indicating higher tremor amplitude of the upper limb. The upper limb total score is the sum of these 6 sub-items and ranges from 0 to 24 where larger values represent higher tremor severity.
Change from baseline to Days 14, 28, and 42 on the TETRAS-CUL score [Up to 42 days]
The combined upper limb score is the sum of the 6 sub-item scores of the upper limb item and the handwriting and spirals scores. The combined upper limb score ranges from 0 to 32 where larger values represent higher tremor severity.
CGI-I scores at Days 14, 28, and 42 [Up to 42 days]
The CGI-I assesses the participant's improvement (or worsening). The clinician is required to assess the participant's condition relative to pre-treatment on a 7-point scale from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement/worsening is drug-related or not.
PGI-C scores at Days 14, 28, and 42 [Up to 42 days]
The PGI-C assesses the participant's improvement (or worsening). The participant is required to assess their condition relative to Baseline (Pre-dose on Day 1) on a 7-point scale from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the participant believes the improvement/worsening is drug-related or not.
Change from baseline to Day 42 on the TETRAS-PS total score [42 days]
There are 9 items covering different body regions in the Performance Subscale. Each Performance Subscale item is rated on a scale of 0 to 4, with higher scores indicating higher tremor severity. Item 4 of the Performance Subscale is the upper limb item. It is comprised of 6 sub-items (4a, 4b, and 4c assessed for both the right and left upper limbs). The Performance subscale score is calculated as the sum of all 9 items and ranges from 0 to 64.
Number of participants with Adverse Events (AE) [Up to 56 days]
The number of participants with Adverse Events (AE) will be reported by preferred term.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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).

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Praxis Research Site	Birmingham	Alabama	United States	35294
2	Praxis Research Site	Little Rock	Arkansas	United States	72205
3	Praxis Research Site	San Diego	California	United States	92103
4	Praxis Research Site	Santa Monica	California	United States	90404
5	Praxis Research Site	Torrance	California	United States	90503
6	Praxis Research Site	Aurora	Colorado	United States	80045
7	Praxis Research Site	Boca Raton	Florida	United States	33486
8	Praxis Research Site	Gainesville	Florida	United States	32608
9	Praxis Research Site	Jacksonville	Florida	United States	32209
10	Praxis Research Site	Port Charlotte	Florida	United States	33980
11	Praxis Research Site	Saint Petersburg	Florida	United States	33713
12	Praxis Research Site	Tampa	Florida	United States	33612
13	Praxis Research Site	West Palm Beach	Florida	United States	33407
14	Praxis Research Site	Atlanta	Georgia	United States	30329
15	Praxis Research Site	Chicago	Illinois	United States	60612
16	Praxis Research Site	Kansas City	Kansas	United States	66160
17	Praxis Research Site	Louisville	Kentucky	United States	40202
18	Praxis Research Site	Rockville	Maryland	United States	20852
19	Praxis Research Site	Boston	Massachusetts	United States	02118
20	Praxis Research Site	Boston	Massachusetts	United States	02135
21	Praxis Research Site	Burlington	Massachusetts	United States	01805
22	Praxis Research Site	Farmington Hills	Michigan	United States	48334
23	Praxis Research Site	Golden Valley	Minnesota	United States	55427
24	Praxis Research Site	Las Vegas	Nevada	United States	89106
25	Praxis Research Site	New York	New York	United States	10029
26	Praxis Research Site	New York	New York	United States	10032
27	Praxis Research Site	Cincinnati	Ohio	United States	45212
28	Praxis Research Site	Cleveland	Ohio	United States	44106
29	Praxis Research Site	Philadelphia	Pennsylvania	United States	19107
30	Praxis Research Site	Nashville	Tennessee	United States	37232
31	Praxis Research Site	Georgetown	Texas	United States	78628
32	Praxis Research Site	Houston	Texas	United States	77030-4202
33	Praxis Research Site	Houston	Texas	United States	77030
34	Praxis Research Site	Round Rock	Texas	United States	78681
35	Praxis Research Site	Burlington	Vermont	United States	05401
36	Praxis Research Site	Alexandria	Virginia	United States	22311
37	Praxis Research Site	Virginia Beach	Virginia	United States	23456
38	Praxis Research Site	Kirkland	Washington	United States	98034
39	Praxis Research Site	Spokane	Washington	United States	99202
40	Praxis Research Site	Milwaukee	Wisconsin	United States	53226
41	Praxis Research Site	Vancouver	British Columbia	Canada	V6T 2B5
42	Praxis Research Site	Halifax	Nova Scotia	Canada	B3S 1N2
43	Praxis Research Site	Toronto	Ontario	Canada	M5T 2S8
44	Praxis Research Site	Montréal	Quebec	Canada	H3A 2B4