A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)
Condition: Uremic Pruritus
MeSH terms: Pruritus
Intervention: CR845 0.5 mcg/kg; Placebo
Intervention description: IV medication delivered three times/week; IV medication delivered three times/week
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 378.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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.
    

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.