Trial Outcomes & Findings for Efficacy and Safety of ETX-018810 for the Treatment of Diabetic Peripheral Neuropathic Pain (NCT NCT04688671)

Last Updated: 2023-11-07

Results Overview

Change from baseline in the weekly average of the daily pain score as derived from the subject's responses on the Pain Intensity Numerical Rating Scale (PI-NRS) a 10 point scale from 0 being the least (No Pain) to 10 being the most (Worst Possible Pain).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

167 participants

Primary outcome timeframe

baseline to Week 4

Results posted on

2023-11-07

Participant Flow

Participant milestones

Participant milestones
Measure	ETX-018810 ETX-018810: Study Drug	Placebo Placebo: Matching Placebo
Overall Study STARTED	83	84
Overall Study COMPLETED	75	80
Overall Study NOT COMPLETED	8	4

Reasons for withdrawal

Reasons for withdrawal
Measure	ETX-018810 ETX-018810: Study Drug	Placebo Placebo: Matching Placebo
Overall Study Adverse Event	3	1
Overall Study Withdrawal by Subject	3	1
Overall Study Lack of Efficacy	1	1
Overall Study Protocol Violation	1	0
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Efficacy and Safety of ETX-018810 for the Treatment of Diabetic Peripheral Neuropathic Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ETX-018810 n=83 Participants ETX-018810: Study Drug	Placebo n=84 Participants Placebo: Matching Placebo	Total n=167 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	57 Participants n=5 Participants	55 Participants n=7 Participants	112 Participants n=5 Participants
Age, Categorical >=65 years	26 Participants n=5 Participants	29 Participants n=7 Participants	55 Participants n=5 Participants
Age, Continuous	60.4 years STANDARD_DEVIATION 9.33 • n=5 Participants	60.3 years STANDARD_DEVIATION 9.87 • n=7 Participants	60.4 years STANDARD_DEVIATION 9.57 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	34 Participants n=7 Participants	59 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	50 Participants n=7 Participants	108 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) White	70 Participants n=5 Participants	65 Participants n=7 Participants	135 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	83 participants n=5 Participants	84 participants n=7 Participants	167 participants n=5 Participants
Body Mass Index (BMI)	31.9 kg/m^2 STANDARD_DEVIATION 4.33 • n=5 Participants	30.9 kg/m^2 STANDARD_DEVIATION 4.77 • n=7 Participants	31.4 kg/m^2 STANDARD_DEVIATION 4.57 • n=5 Participants

PRIMARY outcome

Timeframe: baseline to Week 4

Population: The modified ITT population included all randomized subjects who received at least one dose of study treatment and had at least four post-baseline PI-NRS measurements; 78 and 81 subjects for the ETX-018810 and Placebo groups, respectively. All subjects in this population were included in the statistical analysis comparing the groups. However, the descriptive summary for Week 4 only included those subjects who had measurements at Baseline and Week 4 (74 and 78 subjects, respectively).

Outcome measures

Outcome measures
Measure	ETX-018810 n=74 Participants ETX-018810: Study Drug	Placebo n=78 Participants Placebo: Matching Placebo
Change From Baseline to Week 4 in the Weekly Average of the Daily Pain Score as Derived From the Subject's Responses on the Pain Intensity Numerical Rating Scale (PI-NRS)	-1.79 score on a scale Standard Deviation 2.099	-1.91 score on a scale Standard Deviation 1.781

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 2, 3 and 4

Change in the weekly average of the daily pain score as derived from the subject's responses on the Pain Intensity Numerical Rating Scale (PI-NRS) a 10 point scale from 0 being the least (No Pain) to 10 being the most (Worst Possible Pain).

Outcome measures

Outcome measures
Measure	ETX-018810 n=78 Participants ETX-018810: Study Drug	Placebo n=81 Participants Placebo: Matching Placebo
Number of Subjects With a ≥50% Reduction From Baseline to Weeks 1, 2, 3, and 4 in the Weekly Average of the Daily Pain Score Week 1	5 Participants	1 Participants
Number of Subjects With a ≥50% Reduction From Baseline to Weeks 1, 2, 3, and 4 in the Weekly Average of the Daily Pain Score Week 2	15 Participants	7 Participants
Number of Subjects With a ≥50% Reduction From Baseline to Weeks 1, 2, 3, and 4 in the Weekly Average of the Daily Pain Score Week 3	16 Participants	18 Participants
Number of Subjects With a ≥50% Reduction From Baseline to Weeks 1, 2, 3, and 4 in the Weekly Average of the Daily Pain Score Week 4	16 Participants	25 Participants

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 2, 3 and 4

Outcome measures

Outcome measures
Measure	ETX-018810 n=78 Participants ETX-018810: Study Drug	Placebo n=81 Participants Placebo: Matching Placebo
Number of Subjects With a ≥30% Reduction From Baseline to Weeks 1, 2, 3, and 4 in the Weekly Average of the Daily Pain Score Week 1	11 Participants	9 Participants
Number of Subjects With a ≥30% Reduction From Baseline to Weeks 1, 2, 3, and 4 in the Weekly Average of the Daily Pain Score Week 2	21 Participants	26 Participants
Number of Subjects With a ≥30% Reduction From Baseline to Weeks 1, 2, 3, and 4 in the Weekly Average of the Daily Pain Score Week 3	25 Participants	38 Participants
Number of Subjects With a ≥30% Reduction From Baseline to Weeks 1, 2, 3, and 4 in the Weekly Average of the Daily Pain Score Week 4	26 Participants	42 Participants

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 2 and 3

Outcome measures

Outcome measures
Measure	ETX-018810 n=78 Participants ETX-018810: Study Drug	Placebo n=81 Participants Placebo: Matching Placebo
Change in the Weekly Average of the Daily Pain Score From Baseline to Weeks 1, 2, and 3 Week 1	-0.67 score on a scale Standard Deviation 1.294	-0.51 score on a scale Standard Deviation 1.009
Change in the Weekly Average of the Daily Pain Score From Baseline to Weeks 1, 2, and 3 Week 2	-1.39 score on a scale Standard Deviation 1.879	-1.16 score on a scale Standard Deviation 1.420
Change in the Weekly Average of the Daily Pain Score From Baseline to Weeks 1, 2, and 3 Week 3	-1.60 score on a scale Standard Deviation 1.945	-1.56 score on a scale Standard Deviation 1.682

SECONDARY outcome

Timeframe: Week 4

Population: The ITT population included all randomized subjects who received at least one dose of study treatment; 83 and 84 subjects for the ETX-018810 and Placebo groups, respectively. Not all subjects had a CGI-C assessment.

The Clinical Global Impression - Change (CGI-C) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to the baseline state at the beginning of the intervention. The rater selects one response based on the following question, "Compared to your patient's condition at the beginning of treatment, how much has your patient changed?" Scores are as follows: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; and 7 = very much worse.

Outcome measures

Outcome measures
Measure	ETX-018810 n=81 Participants ETX-018810: Study Drug	Placebo n=83 Participants Placebo: Matching Placebo
Number of Subjects With a CGI-C Response (Defined as "Much Improved" or "Very Much Improved") at Week 4	26 Participants	34 Participants

SECONDARY outcome

Timeframe: Week 4

The Patient Global Impression - Change (PGI-C) is the patient-reported counterpoint to the CGI C (Guy, 1976). The qualitative assessment of meaningful change is determined by the patient in response to the question, "Compared to your condition at the beginning of treatment, how much has your condition changed?" Scores are as follows: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; and 7 = very much worse.

Outcome measures

Outcome measures
Measure	ETX-018810 n=81 Participants ETX-018810: Study Drug	Placebo n=83 Participants Placebo: Matching Placebo
Number of Subjects With a PGI-C Response (Defined as "Much Improved" or "Very Much Improved") at Week 4.	27 Participants	37 Participants

SECONDARY outcome

Timeframe: Baseline to Weeks 1, 2, 3 and 4

The Daily Sleep Interference Scale (DSIS) is an 11-point response scale that quantifies sleep interference due to pain. It is a single-item measure that is completed once daily, upon awakening, to accurately capture variability in sleep interference due to pain on a daily basis, thus minimizing recall bias. Patients are asked to select the number that best describes how much their pain has interfered with their sleep during the last 24 hours on a scale from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep).

Outcome measures

Outcome measures
Measure	ETX-018810 n=78 Participants ETX-018810: Study Drug	Placebo n=81 Participants Placebo: Matching Placebo
Change in the Weekly Average of the Daily Sleep Score on the DSIS From Baseline to Weeks 1, 2, 3, and 4 Week 1	-0.86 score on a scale Standard Deviation 1.554	-0.67 score on a scale Standard Deviation 1.133
Change in the Weekly Average of the Daily Sleep Score on the DSIS From Baseline to Weeks 1, 2, 3, and 4 Week 2	-1.36 score on a scale Standard Deviation 1.967	-1.34 score on a scale Standard Deviation 1.480
Change in the Weekly Average of the Daily Sleep Score on the DSIS From Baseline to Weeks 1, 2, 3, and 4 Week 3	-1.65 score on a scale Standard Deviation 2.087	-1.73 score on a scale Standard Deviation 1.720
Change in the Weekly Average of the Daily Sleep Score on the DSIS From Baseline to Weeks 1, 2, 3, and 4 Week 4	-1.70 score on a scale Standard Deviation 2.144	-1.95 score on a scale Standard Deviation 1.900

SECONDARY outcome

Timeframe: Baseline to Week 4

The BPI Interference scale measures how much pain has interfered with seven daily activities scored on a scale from 0 (does not interfere) to 10 (completely interferes). It is scored as the mean of the seven interference items.

Outcome measures

Outcome measures
Measure	ETX-018810 n=81 Participants ETX-018810: Study Drug	Placebo n=83 Participants Placebo: Matching Placebo
Change in the BPI - Interference Scale From Baseline to Week 4	-1.60 score on a scale Standard Deviation 2.142	-1.78 score on a scale Standard Deviation 2.202

SECONDARY outcome

Timeframe: Baseline to Week 4

The BPI pain scale is a composite of 4 items assessing pain severity (worst, least, average, and right now). Subjects rate their pain in last 24 hours on a scale from 0 (no pain) to 10 (pain as bad as you can imagine). It is scored as the mean of the four pain items.

Outcome measures

Outcome measures
Measure	ETX-018810 n=81 Participants ETX-018810: Study Drug	Placebo n=83 Participants Placebo: Matching Placebo
Change in the BPI-Pain Scale From Baseline to Week 4	-1.39 score on a scale Standard Deviation 1.833	-1.78 score on a scale Standard Deviation 1.809

SECONDARY outcome

Timeframe: Baseline to week 4

The daily amount of acetaminophen (rescue medication) that was used (mg per day).

Outcome measures

Outcome measures
Measure	ETX-018810 n=78 Participants ETX-018810: Study Drug	Placebo n=81 Participants Placebo: Matching Placebo
Change in the Daily Amount of Acetaminophen Use From Baseline to Week 4	0 mg per day Interval -105.9 to 0.0	0 mg per day Interval -92.9 to 0.0

Adverse Events

ETX-018810

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ETX-018810 n=83 participants at risk ETX-018810: Study Drug	Placebo n=84 participants at risk Placebo: Matching Placebo
Cardiac disorders Myocardial ischaemia	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)

Other adverse events

Additional Information

Clinical Operations

Eliem Therapeutics

Phone: +1-888-506-2573

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the PI will provide the sponsor with a copy of any proposed communication at least 90 days in advance of the proposed submission or presentation date. Within this 90 day period, the sponsor will review the communication to determine whether it contains any sponsor Confidential Information, or whether the sponsor desires to file patent applications on subject matter contained therein, and to ensure the accuracy of the information.
Publication restrictions are in place

Restriction type: OTHER

Measure	ETX-018810 n=83 participants at risk ETX-018810: Study Drug	Placebo n=84 participants at risk Placebo: Matching Placebo
Gastrointestinal disorders Diarrhoea	8.4% 7/83 • Number of events 7 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Gastrointestinal disorders Gastrooesophageal reflux disease	2.4% 2/83 • Number of events 2 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Gastrointestinal disorders Nausea	2.4% 2/83 • Number of events 2 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Gastrointestinal disorders Constipation	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	2.4% 2/84 • Number of events 2 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Gastrointestinal disorders Oesophageal pain	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Gastrointestinal disorders Abdominal pain lower	0.00% 0/83 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Infections and infestations cellulitis	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Infections and infestations Gastroenteritis astroviral	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Infections and infestations Respiratory syncytial virus infection	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Infections and infestations Diabetic foot infection	0.00% 0/83 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Infections and infestations Upper respiratory tract infection	0.00% 0/83 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Infections and infestations Urinary tract infection	0.00% 0/83 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Respiratory, thoracic and mediastinal disorders Cough	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Respiratory, thoracic and mediastinal disorders Sinus congestion	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Respiratory, thoracic and mediastinal disorders Nasal pruritus	0.00% 0/83 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Cardiac disorders Atrial fibrillation	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Musculoskeletal and connective tissue disorders Back pain	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Musculoskeletal and connective tissue disorders Myalgia	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Nervous system disorders Headache	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Nervous system disorders Sciatica	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Blood and lymphatic system disorders Anaemia	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Ear and labyrinth disorders Vertigo	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
General disorders Pyrexia	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Metabolism and nutrition disorders Hyperglycaemia	1.2% 1/83 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	0.00% 0/84 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/83 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Investigations Liver function test increased	0.00% 0/83 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/83 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/83 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)	1.2% 1/84 • Number of events 1 • 9 weeks (up to 4 week screening period, 4 week treatment period, & 1 week follow up period)