Evaluation of Efficacy and Safety of VX-548 for Painful Diabetic Peripheral Neuropathy (DPN)

A Phase 2, Randomized, Double-blind, Active-controlled, Dose-ranging, Parallel-design Study of the Efficacy and Safety of VX-548 in Subjects With Painful Diabetic Peripheral Neuropathy

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05660538

Enrollment

194

Registered

2022-12-21

Start date

2022-12-20

Completion date

2023-10-25

Last updated

2025-07-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetic Peripheral Neuropathy

Brief summary

The purpose of this study is to evaluate the efficacy and safety of VX-548 doses in treating Painful DPN.

Interventions

DRUGSuzetrigine

Tablets for oral administration.

DRUGPregabalin

Capsules for oral administration.

DRUGPlacebo (matched to SUZ)

Placebo matched to SUZ for oral administration.

DRUGPlacebo (matched to pregabalin)

Placebo matched to pregabalin for oral administration.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Diagnosis of diabetes mellitus type 1 or type 2 with * Glycosylated hemoglobin A1c (HbA1c) ≤9%; and * Presence of bilateral pain in lower extremities due to DPN for at least 1 year Key

Exclusion criteria

* Painful neuropathy other than DPN * History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s) * History of a clinical atherosclerotic event, such as myocardial infarction or stroke, within the past 12 months Other protocol defined Inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in the Weekly Average of Daily Pain Intensity on a Numeric Pain Rating Scale (NPRS)	Baseline, At Week 12	Change from baseline in the weekly mean of the daily Numeric Pain Rating Scale (NPRS) score assessing average pain intensity in the last 24 hours. Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain.

Secondary

Measure	Time frame	Description
Percentage of Participants With Greater Than or Equal to (≥) 30 Percent Reduction From Baseline in the Weekly Average of Daily Pain Intensity on the NPRS	Baseline, At Week 12	Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The percentage of participants with ≥30% reduction from baseline in the weekly average NPRS score at Week 12 was reported.
Percentage of Participants With ≥50 Percent Reduction From Baseline in the Weekly Average of Daily Pain Intensity on the NPRS	Baseline, At Week 12	Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain.The percentage of participants with ≥50% reduction from baseline in the weekly average NPRS score at Week 12 was reported.
Change From Baseline in the Weekly Average of the Daily Sleep Interference Scale (DSIS) Score	Baseline, At Week 12	Change from baseline in the weekly mean of the Daily Sleep Interference Scale (DSIS) score, which asks participants to describe how pain interfered with the participant's sleep. Response options for the DSIS range from 0 (none) to 10 (severe).
Percentage of Participants Categorized as Much Improved or Very Much Improved on the Patient Global Impression of Change (PGIC) Assessment	Baseline, At Week 12	PGIC is an instrument that measures change in participants' overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Day 1 up to Week 14	—
Percentage of Participants With ≥70 Percent Reduction From Baseline in the Weekly Average of Daily Pain Intensity on the NPRS	Baseline, At Week 12	Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The percentage of participants with ≥70% reduction from baseline in the weekly average NPRS score at Week 12 was reported.

Countries

United States

Participant flow

Pre-assignment details

A total of 194 participants were randomized in this study, out of which 192 participants received the study drug. Of these 192 participants, 19 participants from one of the sites were excluded due to lack of compliance with the study drug. Therefore, 173 participants are reported below for Baseline section and Efficacy outcomes and 192 participants are reported for Safety outcome and Adverse event section.

Participants by arm

Arm	Count
Pregabalin Participants received Pregabalin 100 mg tid for 12 weeks.	49
Suzetrigine (SUZ): Low Dose Participants received SUZ 23 mg tablet qd for 12 weeks.	24
Suzetrigine (SUZ): Mid Dose Participants received SUZ 46 mg tablet qd for 12 weeks.	50
Suzetrigine (SUZ): High Dose Participants received SUZ 69 mg tablet qd for 12 weeks.	50
Total	173

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	0	0	1	0
Overall Study	Death	0	0	1	0
Overall Study	Enrolled at clinical trial site excluded from mFAS due to lack of compliance with study drug	5	4	5	5
Overall Study	Lost to Follow-up	0	0	1	1
Overall Study	Other	1	0	0	1
Overall Study	Physician Decision	0	0	0	1
Overall Study	Randomized but did not receive study drug	1	0	0	1
Overall Study	Sponsor Decision	1	0	0	0
Overall Study	Withdrawal of consent (not due to AE)	1	0	1	0

Baseline characteristics

Characteristic	Pregabalin	Suzetrigine (SUZ): Low Dose	Suzetrigine (SUZ): Mid Dose	Suzetrigine (SUZ): High Dose	Total
Age, Continuous	63.0 years STANDARD_DEVIATION 7.9	60.9 years STANDARD_DEVIATION 6.6	61.7 years STANDARD_DEVIATION 8.6	61.4 years STANDARD_DEVIATION 8.8	61.9 years STANDARD_DEVIATION 8.2
Baseline Weekly Average Pain Intensity as Recorded on Numeric Pain Rating Scale (NPRS)	5.99 units on a scale STANDARD_DEVIATION 1.27	5.70 units on a scale STANDARD_DEVIATION 1.32	5.88 units on a scale STANDARD_DEVIATION 0.97	5.83 units on a scale STANDARD_DEVIATION 1.23	5.87 units on a scale STANDARD_DEVIATION 1.18
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants	0 Participants	0 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized Asian	0 Participants	0 Participants	2 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized Black or African American	16 Participants	7 Participants	15 Participants	14 Participants	52 Participants
Race/Ethnicity, Customized Hispanic or Latino	7 Participants	2 Participants	9 Participants	4 Participants	22 Participants
Race/Ethnicity, Customized Multiracial	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	42 Participants	22 Participants	41 Participants	46 Participants	151 Participants
Race/Ethnicity, Customized Other	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized White	32 Participants	15 Participants	33 Participants	35 Participants	115 Participants
Sex: Female, Male Female	22 Participants	12 Participants	22 Participants	21 Participants	77 Participants
Sex: Female, Male Male	27 Participants	12 Participants	28 Participants	29 Participants	96 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 54	0 / 28	1 / 55	0 / 55
other Total, other adverse events	12 / 54	4 / 28	5 / 55	7 / 55
serious Total, serious adverse events	1 / 54	0 / 28	2 / 55	1 / 55

Outcome results

Primary

Change From Baseline in the Weekly Average of Daily Pain Intensity on a Numeric Pain Rating Scale (NPRS)

Change from baseline in the weekly mean of the daily Numeric Pain Rating Scale (NPRS) score assessing average pain intensity in the last 24 hours. Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain.