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

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.

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.