a study to evaluate the safety and efficacy of cr845 in hemodialysis patients with moderate-to-severe pruritus (kalm-1)

Conditions: Uremic Pruritus

Summary: 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.

double-blind phase the double-blind phase of the study will consist of a screening visit, a 7-day run-in period, a 12 week double-blind treatment period, and a 2-week discontinuation period. informed consent will be obtained prior to performing any study-specific procedures. the screening visit will occur within 7 to 28 days prior to randomization to assess eligibility. open-label extension phase patients who received at least 30 doses of study drug (either active or placebo) during the 12-week double-blind treatment period and continue to meet other eligibility criteria will have the option to receive open label cr845 for an additional 52 weeks. the open-label extension phase will be comprised of the open-label treatment period and the follow-up period. the last dose of open-label study drug will be administered at the last dialysis visit on week 52, or early termination. a final safety follow up visit will be conducted 7-10 days after the end of treatment/early termination visit.

Eligibility criteria:
key inclusion criteria: to be eligible for inclusion into the double-blind phase of the study, a patient must meet the following criteria: * has end-stage renal disease (esrd) and has been on hemodialysis 3 times per week for at least 3 months prior to the start of screening; * has at least 2 single-pool kt/v measurements ≥1.2, or at least 2 urea reduction ratio measurements ≥65%, or 1 single pool kt/v measurement ≥1.2 and 1 urea reduction ratio measurement ≥65% on different dialysis days during the 3 months period prior to screening; * prior to randomization: * has completed worst itching intensity nrs worksheets up to 8 days prior to 1st dose; * has a mean baseline worst itching intensity nrs indicative of moderate to severe uremic pruritus. * to be eligible for inclusion into the open-label extension phase of the study, each patient will have to fulfill the additional key following criteria at the time of entry into the open-label extension phase: * has received at least 30 doses of the planned 36 doses of study drug during the double-blind phase of this study; * continues to meet inclusion criteria. key exclusion criteria: a patient will be excluded from the double-blind phase of the study if any of the following criteria are met: * known noncompliance with dialysis treatment that in the opinion of the investigator would impede completion or validity of the study; * scheduled to receive a kidney transplant during the study; * new or change of treatment received for itch including antihistamines and corticosteroids (oral, iv, or topical) within 14 days prior to screening; * received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study; * has pruritus only during the dialysis session (by patient report); * is receiving ongoing ultraviolet b and anticipates receiving such treatment during the study; * participated in a previous clinical study with cr845. * a patient will be excluded from the open-label extension phase of the study if any of the additional key following criteria are met at the time of entry into the open-label extension phase: * completed the double-blind phase of this study but exhibited adverse events during the course of the treatment period that may preclude continued exposure to the study drug; * was noncompliant with protocol procedures during the double-blind phase of this study which is indicative of an inability to follow protocol procedures.

Keywords: cr845 pruritus chronic itch itch itching difelikefalin hemodialysis uremic pruritus dialysis ckd ckd-associated pruritus ckd-ap esrd (end stage renal disease) kalm chronic kidney disease kidney failure, chronic kidney dysfunction generalized pruritus