Last reviewed · How we verify

NCT03422653

A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)

Completed Phase 3 Results posted Last updated 26 April 2022
What this trial tests

Phase 3 trial testing CR845 0.5 mcg/kg in Uremic Pruritus in 378 participants. Completed in 26 March 2020.

Timeline
20 February 2018
Primary endpoint
6 April 2019
26 March 2020

Quick facts

Lead sponsorCara Therapeutics, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment378
Start date20 February 2018
Primary completion6 April 2019
Estimated completion26 March 2020
Sites57 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Cara Therapeutics, Inc. — full company profile →

Who can join

18 and older, any sex, with Uremic Pruritus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score at Week 12 Primary · Week 12

Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". LS means estimated percent, odds ratio and P value used a logistic regression model.

GroupValue95% CI
CR845 0.5mcg/kg51.042.9 – 58.9
Placebo27.620.2 – 36.6
Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in 5-D Itch Scale Score at the End of Week 12 Secondary · Baseline, Week 12

The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the degree, duration of itch/day, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. The 5-D Itch Scale has 5 questions; the total 5-D Itch Scale score ranges from 5 to 25, with higher scores indicating worse responses.

GroupValue95% CI
Double-blind CR845 0.5mcg/kg-5.0-5.7 – -4.4
Double-blind Placebo-3.7-4.4 – -3.1
Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in Total Skindex-10 Scale Score at the End of Week 12 Secondary · Baseline, Week 12

The Skindex-10 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. The Skindex-10 has 10 questions; the total Skindex-10 score ranges from 0 to 60. A lower total score represents better quality of life.

GroupValue95% CI
Double-blind CR845 0.5mcg/kg-17.2-19.6 – -14.7
Double-blind Placebo-12.0-14.5 – -9.6
Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥4 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score at Week 12 Secondary · Week 12

Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". LS means estimated percent, odds ratio and P value used a logistic regression model.

GroupValue95% CI
Double-blind CR845 0.5mcg/kg38.929.8 – 48.7
Double-blind Placebo18.012.1 – 26.0

Adverse events — posted to ClinicalTrials.gov

Time frame: The period of adverse event reporting will start after the signing of the informed consent form (ICF) through the study Follow-up Visit or Early Termination Visit (or 7 days after the last dose if no Early Termination Visit was conducted).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Double-blind CR845 0.5mcg/kg
Serious: 49/189 (26%)
Deaths: 2/189
Double-blind Placebo
Serious: 41/188 (22%)
Deaths: 2/188
Open-label CR845 0.5 mcg/kg
Serious: 167/313 (53%)
Deaths: 22/313

Serious adverse events (242 terms)

ReactionSystemDouble-blind CR845 0.5mcg/kgDouble-blind PlaceboOpen-label CR845 0.5 mcg/kg
PneumoniaInfections and infestations
Fluid overloadMetabolism and nutrition disorders
HyperkalaemiaMetabolism and nutrition disorders
Cardiac failure congestiveCardiac disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
SepsisInfections and infestations
Metabolic encephalopathyNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Mental status changesPsychiatric disorders
AstheniaGeneral disorders
Complication associated with deviceGeneral disorders
HypotensionVascular disorders
Hypertensive crisisVascular disorders
SyncopeNervous system disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
Non-cardiac chest painGeneral disorders
Cardiac arrestCardiac disorders
Abdominal painGastrointestinal disorders
Septic shockInfections and infestations
CellulitisInfections and infestations
Vascular access malfunctionInjury, poisoning and procedural complications
Angina pectorisCardiac disorders
Acute myocardial infarctionCardiac disorders
Gastrointestinal haemorrhageGastrointestinal disorders
FallInjury, poisoning and procedural complications
Other adverse events (22 terms — click to expand)

ReactionSystemDouble-blind CR845 0.5mcg/kgDouble-blind PlaceboOpen-label CR845 0.5 mcg/kg
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
FallInjury, poisoning and procedural complications
HypotensionVascular disorders
VomitingGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
DizzinessNervous system disorders
HyperkalaemiaMetabolism and nutrition disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
NasopharyngitisInfections and infestations
Pain in extremityMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
HypertensionVascular disorders
Back painMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
PyrexiaGeneral disorders
Abdominal pain upperGastrointestinal disorders
AnxietyPsychiatric disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Pneumonia, Fluid overload, Hyperkalaemia, Cardiac failure congestive, Respiratory failure, Sepsis, Metabolic encephalopathy, Dyspnoea.

Data from ClinicalTrials.gov NCT03422653 adverse events section.

Sponsor's own description

This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of intravenous (IV) CR845 at a dose of 0.5 mcg/kg administered after each dialysis session. The study includes a 12-week Double-blind Phase and a 52-week Open-label Extension Phase.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus.
    Fishbane S, Jamal A, Munera C, Wen W, et al · · 2020 · cited 234× · PMID 31702883 · DOI 10.1056/nejmoa1912770
  2. Efficacy of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis of KALM-1 and KALM-2 Phase 3 Studies.
    Topf J, Wooldridge T, McCafferty K, Schömig M, et al · · 2022 · cited 59× · PMID 36016762 · DOI 10.1016/j.xkme.2022.100512
  3. Interventions for itch in people with advanced chronic kidney disease.
    Hercz D, Jiang SH, Webster AC. · · 2020 · cited 49× · PMID 33283264 · DOI 10.1002/14651858.cd011393.pub2
  4. Role of kappa-opioid and mu-opioid receptors in pruritus: Peripheral and central itch circuits.
    Kim BS, Inan S, Ständer S, Sciascia T, et al · · 2022 · cited 37× · PMID 36054458 · DOI 10.1111/exd.14669
  5. Safety and Tolerability of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis From the Phase 3 Clinical Trial Program.
    Fishbane S, Wen W, Munera C, Lin R, et al · · 2022 · cited 34× · PMID 36039153 · DOI 10.1016/j.xkme.2022.100513
  6. Difelikefalin in the Treatment of Chronic Kidney Disease-Associated Pruritus: A Systematic Review.
    Wala K, Szepietowski JC. · · 2022 · cited 22× · PMID 36015082 · DOI 10.3390/ph15080934
  7. The relationship between chronic kidney disease-associated pruritus and health-related quality of life: a systematic review.
    Poku E, Harnan S, Rooney G, James MM, et al · · 2022 · cited 21× · PMID 35211305 · DOI 10.1093/ckj/sfab218
  8. Signaling underlying kappa opioid receptor-mediated behaviors in rodents.
    Liu-Chen LY, Huang P. · · 2022 · cited 15× · PMID 36408401 · DOI 10.3389/fnins.2022.964724

Verify or expand the search:

Other trials of CR845 0.5 mcg/kg

Trials testing the same drug.

Other recruiting trials for Uremic Pruritus

Currently open trials in the same condition.

Other Cara Therapeutics, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03422653.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing