Influence of Baseline Itch Severity on Treatment Outcomes With Difelikefalin in Adults With Moderate-to-Severe Pruritus Receiving Maintenance Haemodialysis: An Exploratory Analysis.

McCafferty K, Schaufler T, Molina P, Lowe M, Wen W, Weiner DE

Journal of renal care1 Jun 2025Cited by 1 (Europe PMC)

PMID40327387DOI10.1111/jorc.70017PepBankPUB-40327387

Publisher page PubMedAsk about this study

Summary

BackgroundDifelikefalin is well-tolerated and reduces itch among adults undergoing haemodialysis (HD), with chronic kidney disease-associated pruritus (CKD-aP).ObjectiveThis study aims to explore the influence of baseline itch severity on difelikefalin treatment outcomes.DesignStudy 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg. We report key endpoints from 3105 by baseline itch severity, determined using the Worst Itching Intensity Numerical Rating Scale (WI-NRS [moderate: WI-NRS < 7; severe: WI-NRS ≥ 7]).ParticipantsAdult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).MeasurementsThe primary endpoint of 3105 was safety; secondary endpoints included reduction in itch intensity (WI-NRS), and improvements in itch-related quality of life (QoL; 5-D itch scale) and sleep quality (Sleep Quality Numerical Rating Scale).FindingsMean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI-NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (n = 70/222) or severe (n = 152/222) itch, respectively. No treatment-related deaths occurred, and there were no safety concerns according to baseline itch severity. By week 12, both groups reported residual 'mild itch' according to mean (SD) WI-NRS scores (moderate: 2.9 [2.2]; severe: 3.1 [2.3]). Approximately one in four participants demonstrated 'complete response' in itch reduction (moderate: 27.1%; severe: 25.0%). Clinically relevant improvements in itch-related QoL and sleep quality occurred among both subgroups.ConclusionsDifelikefalin was well-tolerated and effective in reducing itch in participants with moderate and severe baseline itch, supporting its broad use in a range of individuals on HD with CKD-aP.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

10 results from studies that gave the peptide. 10 results from people.

01HumanNon-randomized trialSafety outcome
In haemodialysis adults receiving difelikefalin, no treatment-related deaths occurred.
In plain wordsIn adults on haemodialysis receiving difelikefalin, no treatment-related deaths occurred.
Peptide
Difelikefalin
Outcome
Not applicableTreatment-related deaths
Study
n = 222
Analysis
Primary
Outcome group
Mortality · Whole body
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Source sentences
Summary
No treatment-related deaths occurred, and there were no safety concerns according to baseline itch severity.
2 context sentences(design, population, supporting numbers)
Summary · context
Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg.
Summary · context
Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).
Show in the study text Report a problemFND-4032738701
02HumanNon-randomized trialSafety outcome
In haemodialysis adults receiving difelikefalin, no safety concerns were identified according to baseline itch severity.
In plain wordsIn adults on haemodialysis receiving difelikefalin, safety concerns did not emerge according to initial itch severity.
Peptide
Difelikefalin
Outcome
Not applicableSafety by baseline itch severity
Study
n = 222
Comparator
Moderate versus severe baseline itch
Analysis
Primary
Outcome group
Adverse events · Whole body
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Source sentences
Summary
No treatment-related deaths occurred, and there were no safety concerns according to baseline itch severity.
2 context sentences(design, population, supporting numbers)
Summary · context
Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg.
Summary · context
Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).
Show in the study text Report a problemFND-4032738702
03HumanNon-randomized trialEfficacy outcome
In haemodialysis adults with severe baseline itch receiving difelikefalin, mean Week 12 WI-NRS was 3.1 with standard deviation 2.3.
In plain wordsIn adults on haemodialysis with severe initial itching, itch scores decreased during difelikefalin treatment.
Peptide
Difelikefalin
Outcome
DecreaseWeek 12 WI-NRS in severe baseline itch
Study
n = 152
Analysis
Exploratory
Outcome group
Skin and hair · Skin and wound
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Measurements
WI-NRS mean
3.1 points
week 12; severe baseline itch
WI-NRS SD
2.3 points
week 12; severe baseline itch
WI-NRS mean
8.3 points
baseline; severe itch
WI-NRS SD
0.9 points
baseline; severe itch
Source sentences
Summary
By week 12, both groups reported residual 'mild itch' according to mean (SD) WI-NRS scores (moderate: 2.9 [2.2]; severe: 3.1 [2.3]).
3 context sentences(design, population, supporting numbers)
Summary · context
Mean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI-NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (n = 70/222) or severe (n = 152/222) itch, respectively.
Summary · context
Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg.
Summary · context
Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).
Show in the study text Report a problemFND-4032738704
04HumanNon-randomized trialEfficacy outcome
In haemodialysis adults with severe baseline itch, 25.0% demonstrated complete itch response during difelikefalin treatment.
In plain wordsIn adults on haemodialysis with severe initial itching, some achieved complete itch relief during difelikefalin treatment.
Peptide
Difelikefalin
Outcome
Not applicableComplete itch response in severe baseline itch
Study
n = 152
Analysis
Exploratory
Outcome group
Skin and hair · Skin and wound
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Measurements
Complete response
25%
severe baseline itch
Source sentences
Summary
Approximately one in four participants demonstrated 'complete response' in itch reduction (moderate: 27.1%; severe: 25.0%).
3 context sentences(design, population, supporting numbers)
Summary · context
Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg.
Summary · context
Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).
Summary · context
Mean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI-NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (n = 70/222) or severe (n = 152/222) itch, respectively.
Show in the study text Report a problemFND-4032738706
05HumanNon-randomized trialEfficacy outcome
In haemodialysis adults with severe baseline itch, itch-related quality of life improved clinically during difelikefalin treatment.
In plain wordsIn adults on haemodialysis with severe initial itching, itch-related quality of life improved during difelikefalin treatment.
Peptide
Difelikefalin
Outcome
Direction not reportedItch-related quality of life in severe baseline itch
Study
n = 152
Analysis
Exploratory
Outcome group
Skin and hair · Skin and wound
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Source sentences
Summary
Clinically relevant improvements in itch-related QoL and sleep quality occurred among both subgroups.
3 context sentences(design, population, supporting numbers)
Summary · context
Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg.
Summary · context
Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).
Summary · context
Mean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI-NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (n = 70/222) or severe (n = 152/222) itch, respectively.
Show in the study text Report a problemFND-4032738708
06HumanNon-randomized trialEfficacy outcome
In haemodialysis adults with severe baseline itch, sleep quality improved clinically during difelikefalin treatment.
In plain wordsIn adults on haemodialysis with severe initial itching, sleep quality improved during difelikefalin treatment.
Peptide
Difelikefalin
Outcome
Direction not reportedSleep quality in severe baseline itch
Study
n = 152
Analysis
Exploratory
Outcome group
Sleep · Sleep
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Source sentences
Summary
Clinically relevant improvements in itch-related QoL and sleep quality occurred among both subgroups.
3 context sentences(design, population, supporting numbers)
Summary · context
Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg.
Summary · context
Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).
Summary · context
Mean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI-NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (n = 70/222) or severe (n = 152/222) itch, respectively.
Show in the study text Report a problemFND-4032738710
07HumanNon-randomized trialEfficacy outcome
In haemodialysis adults with moderate baseline itch receiving difelikefalin, mean Week 12 WI-NRS was 2.9 with standard deviation 2.2.
In plain wordsIn adults on haemodialysis with moderate initial itching, itch scores decreased during difelikefalin treatment.
Peptide
Difelikefalin
Outcome
DecreaseWeek 12 WI-NRS in moderate baseline itch
Study
n = 70
Analysis
Exploratory
Outcome group
Skin and hair · Skin and wound
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Measurements
WI-NRS mean
2.9 points
week 12; moderate baseline itch
WI-NRS SD
2.2 points
week 12; moderate baseline itch
WI-NRS mean
6 points
baseline; moderate itch
WI-NRS SD
0.5 points
baseline; moderate itch
Source sentences
Summary
By week 12, both groups reported residual 'mild itch' according to mean (SD) WI-NRS scores (moderate: 2.9 [2.2]; severe: 3.1 [2.3]).
3 context sentences(design, population, supporting numbers)
Summary · context
Mean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI-NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (n = 70/222) or severe (n = 152/222) itch, respectively.
Summary · context
Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg.
Summary · context
Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).
Show in the study text Report a problemFND-4032738703
08HumanNon-randomized trialEfficacy outcome
In haemodialysis adults with moderate baseline itch, 27.1% demonstrated complete itch response during difelikefalin treatment.
In plain wordsIn adults on haemodialysis with moderate initial itching, some achieved complete itch relief during difelikefalin treatment.
Peptide
Difelikefalin
Outcome
Not applicableComplete itch response in moderate baseline itch
Study
n = 70
Analysis
Exploratory
Outcome group
Skin and hair · Skin and wound
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Measurements
Complete response
27.1%
moderate baseline itch
Source sentences
Summary
Approximately one in four participants demonstrated 'complete response' in itch reduction (moderate: 27.1%; severe: 25.0%).
3 context sentences(design, population, supporting numbers)
Summary · context
Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg.
Summary · context
Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).
Summary · context
Mean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI-NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (n = 70/222) or severe (n = 152/222) itch, respectively.
Show in the study text Report a problemFND-4032738705
09HumanNon-randomized trialEfficacy outcome
In haemodialysis adults with moderate baseline itch, itch-related quality of life improved clinically during difelikefalin treatment.
In plain wordsIn adults on haemodialysis with moderate initial itching, itch-related quality of life improved during difelikefalin treatment.
Peptide
Difelikefalin
Outcome
Direction not reportedItch-related quality of life in moderate baseline itch
Study
n = 70
Analysis
Exploratory
Outcome group
Skin and hair · Skin and wound
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Source sentences
Summary
Clinically relevant improvements in itch-related QoL and sleep quality occurred among both subgroups.
3 context sentences(design, population, supporting numbers)
Summary · context
Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg.
Summary · context
Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).
Summary · context
Mean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI-NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (n = 70/222) or severe (n = 152/222) itch, respectively.
Show in the study text Report a problemFND-4032738707
10HumanNon-randomized trialEfficacy outcome
In haemodialysis adults with moderate baseline itch, sleep quality improved clinically during difelikefalin treatment.
In plain wordsIn adults on haemodialysis with moderate initial itching, sleep quality improved during difelikefalin treatment.
Peptide
Difelikefalin
Outcome
Direction not reportedSleep quality in moderate baseline itch
Study
n = 70
Analysis
Exploratory
Outcome group
Sleep · Sleep
Studied dose
0.5 µg/kg · 12 weeksAs given in this study (human).
Source sentences
Summary
Clinically relevant improvements in itch-related QoL and sleep quality occurred among both subgroups.
3 context sentences(design, population, supporting numbers)
Summary · context
Study 3105 (NCT03998163) was a 12-week, phase 3, single-arm, open-label trial assessing safety and effectiveness of difelikefalin 0.5 µg/kg.
Summary · context
Adult participants undergoing maintenance HD (n = 222) with mild-to-moderate CKD-aP (WI-NRS score ≥ 5 at baseline).
Summary · context
Mean (SD) age was 57.1 (13.3) years; mean (SD) baseline WI-NRS scores were 6.0 (0.5) and 8.3 (0.9) for participants with moderate (n = 70/222) or severe (n = 152/222) itch, respectively.
Show in the study text Report a problemFND-4032738709

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:35 UTC
First added · source update from Europe PMC

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