Extension Study to Evaluate IV CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

This is an open-label multicenter, long-term extension safety study to evaluate the safety of
IV CR845 administered after each dialysis session over a Treatment Period of up to 52 weeks.
This study will consist of a Screening Visit, a 52 week Treatment Period, and a Follow-up
Visit. Informed consent will be obtained prior to performing any study-specific procedures.
All patients will have a Screening Visit, which can be performed anytime within 14 days prior
to the first dose of study drug, to confirm eligibility.

Clinical laboratory tests, electrocardiograms (ECGs), vital signs, adverse events, and
concomitant medications will be monitored throughout the study. Blood samples for
inflammatory biomarkers will be collected from all patients prior to dialysis on Day 1 and
periodically until the End of Treatment or Early Termination Visit. Blood samples will also
be collected periodically for clinical laboratory tests.

Inclusion Criteria:

To be eligible for inclusion into the study, a patient must meet the following criteria:

1. Willing and able to provide written informed consent prior to participating in this
study;

2. Able to communicate clearly with the Investigator and staff, able to understand the
study procedures, and able and willing to comply with the study schedules and all
study requirements;

3. Males or females 18 years of age or older;

4. Currently on hemodialysis for end-stage renal disease and has been categorized as
experiencing moderate to severe uremic pruritus;

5. If female:

1. Is not of childbearing potential (surgically sterile or postmenopausal, as
defined in Section 6.5.1.6); or

2. Has a negative serum pregnancy test at screening and agrees to use acceptable
contraceptive measures (as defined in Section 6.5.1.6) from the time of informed
consent until the safety Follow-up Visit or 7 days after the last dose of study
drug, whichever is later.

6. If male, agrees not to donate sperm after the first dose of study drug until 7 days
after the last dose, and agrees to use a condom with spermicide or abstain from
heterosexual intercourse during the study until 7 days after study drug
administration. (Note: No restrictions are required for a vasectomized male provided
his vasectomy was performed ≥4 months prior to dosing);

7. Has a dry body weight of ≥40.0 kg at screening (prescription target dry body weight);

8. Has adequacy of dialysis, defined as meeting 1 of the following criteria during the 3
months prior to screening:

1. ≥2 single pool Kt/V measurements ≥1.2; or

2. ≥2 urea reduction ratio measurements ≥65%; or

3. 1 single pool Kt/V measurement ≥1.2 and 1 urea reduction ratio measurement ≥65%

Exclusion Criteria:

A patient will be excluded from the study if any of the following criteria are met:

1. Received an investigational drugwithin 30 days prior to the first dose of study drug,
or is planning to participate in another interventional clinical study while enrolled
in this study.

2. Has a concomitant disease or any medical condition that, in the opinion of the
Investigator, could pose undue risk to the patient, impede completion of the study
procedures, or would compromise the validity of the study measurements, including, but
not limited to:

1. Known or suspected history of Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition, -diagnosed alcohol, narcotic or other drug abuse, or
substance dependence within 12 months prior to screening;

2. New York Heart Association Class IV congestive heart failure (Appendix 1, Section
14.0);

3. Severe mental illness or cognitive impairment (eg, dementia);

4. Any other relevant acute or chronic medical or neuropsychiatric condition;