CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-2)

Cara Therapeutics

Status and phase: Completed; Phase 3

Conditions: Uremic Pruritus

Treatments: Drug: CR845 0.5 mcg/kg; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03636269

CR845-CLIN3103

Details and patient eligibility

About

This is a multicenter, international 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 randomized, double-blind, placebo-controlled Phase and a 52-week Open-label Extension Phase.

Full description

Double-blind Phase: The Double-blind Phase of the study will consist of a Screening Visit, a 7-day Run-in Period, and a 12-week Double-blind Treatment 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 last dose of open-label study drug will be administered at the last dialysis visit on Week 52, or Early Termination.

Follow-up Period: A final safety Follow up Visit will be conducted 7-10 days after the End of Treatment/Early Termination Visit.

Enrollment: 473 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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473 participants in 2 patient groups, including a placebo group

CR845 0.5mcg/kg

Active Comparator group

Description:

IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)

Treatment:

Drug: CR845 0.5 mcg/kg

Placebo

Placebo Comparator group

Description:

IV Placebo administered after each dialysis session (3 times/week)

Treatment:

Drug: Placebo