A Study to Evaluate the Safety and Effectiveness of Intravenous CR845 in Hemodialysis Patients with Moderate-to-Severe Pruritus

Phase 1

Conditions: Moderate-to-Severe Pruritus in Hemodialysis Patients
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2018-004572-35-PL

Lead Sponsor: Cara Therapeutics INC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 400

Inclusion 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 requirements, including providing written responses to questionnaires;
3. Male or female between 18 and 85 years of age, inclusive;
4. 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;
Note 1: Patients who require an occasional additional dialysis treatment to manage fluid overload or electrolyte excesses may be enrolled as long as it is anticipated that no more than 1 such treatment will be required in any given week. Patients routinely on 4 dialyses a week will not be eligible.
Note 2: Patients receiving in-home hemodialysis may participate as long as they have switched to in-center hemodialysis at least 2 weeks prior to screening and plan to remain on in-center hemodialysis for the duration of the study.
Note 3: Patients receiving alternate dialysis modalities such as nocturnal dialysis will not be eligible.
5. If female, is not pregnant or nursing during any period of the study;
6. If female:
a. Is surgically sterile; or
b. Has been amenorrhoeic for at least 1 year and is over the age of 55 years; or
c. Has a negative serum pregnancy test within 7 days of administration of the first dose of study drug and agrees to use acceptable contraceptive measures (eg, hormonal contraceptives, barrier with spermicide, intrauterine device, vasectomized partner, or
abstinence from heterosexual intercourse) from the time of informed consent until 7 days after the last dose of study drug;
7. If male, agrees not to donate sperm after the first dose of study drug until 7 days after the last dose of study drug, and agrees to
use a condom with spermicide or abstain from heterosexual intercourse during the study until 7 days after the last dose of study drug;
Note: No restrictions are required for a vasectomized male provided his vasectomy was performed =4 months prior to screening.
8. Has a prescription dry body weight =40 kg;
9. Over the last three months prior to screening, has had at least one of the following:
a. At least 2 single-pool Kt/V measurements =1.2 on different dialysis days;
b. At least 2 urea reduction ratio measurements =65% on different dialysis days;
c. 1 single-pool Kt/V measurement =1.2 and 1 urea reduction ratio measurement =65% on different dialysis days;
10. Prior to treatment:
a. Has completed at least three Worst Itching Intensity Numerical Rating Scale (NRS) questionnaires from the start of the Run-in Period up to and including the predose assessment on Day 1;
b. Has a mean baseline Worst Itching Intensity NRS score = 5, defined as the average of all non-missing scores reported from the start of the Run-in Period up to and including the pre-dose assessment on Day 1.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) ye

Exclusion Criteria

1. Known noncompliance with dialysis treatment that in the opinion of the Investigator would impede completion or validity of the study;
2. Scheduled to receive a kidney transplant during the study;
3. Known history of allergic reaction to opiates, such as hives;
Note: side effects related to the use of opioids, such as constipation or nausea, would not exclude patients from the study.
4. Hypersensitivity to the active substance or any of the excipients in the investigational products;
5. Has a concomitant disease or a history of 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:
a. Known or suspected history of alcohol, narcotic, or other drug abuse, or substance dependence within 12 months prior to screening;
b. Significant systolic or diastolic heart failure (eg, New York Heart Association Class IV congestive heart failure [Appendix 1, Section 14.1]);
c. Severe mental illness or cognitive impairment (eg, dementia);
d. Any other relevant acute or chronic medical or neuropsychiatric condition within 3 months prior to screening (eg, diagnosis of encephalopathy, coma,
delirium);
6. New or change of treatment received for itch including antihistamines and corticosteroids (oral, IV, or topical) within 14 days prior to screening;
7. New or change of prescription for opioids, gabapentin, or pregabalin within 14 days prior to screening;
8. Received another investigational drug within 30 days or five half-lives (whichever is longer) prior to the start of dosing or is planning to participate in another interventional clinical study while enrolled in this study;
9. In the opinion of the Investigator, has pruritus attributed to a cause other than ESRD or its complications (eg, patients with concomitant pruritic dermatological disease or cholestatic liver disease);
Note: Patients whose pruritus is attributed to ESRD complications, such as hyperparathyroidism, hyperphosphatemia, anemia, or the dialysis procedure or prescription may be enrolled.
10. Has localized itch restricted to the palms of the hands;
11. Has pruritus only during the dialysis session (by patient report);
12. Is receiving ongoing ultraviolet B treatment and/or anticipates receiving such treatment during the study;
13. Participated in a previous clinical study with CR845.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: To evaluate the safety of IV CR845 at a dose of 0.5 mcg/kg in hemodialysis patients with moderate-to-severe pruritus<br> ;<br> Secondary Objective: To evaluate the effectiveness of IV CR845 at a dose of 0.5 mcg/kg in reducing the intensity of itch in hemodialysis patients with moderate-to-severe pruritus To evaluate the effectiveness of IV CR845 at a dose of 0.5 mcg/kg in improving itch-related quality-of-life and quality of sleep measures in hemodialysis patients with moderate-tosevere pruritus.<br><br> ;<br> Primary end point(s): Safety Endpoints<br> • Adverse events<br> • ECG<br> • Vital signs<br> • Clinical laboratory values<br> ;Timepoint(s) of evaluation of this end point: Refer to Table 2 Schedule of Events on page 32 of the Protocol

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Refer to Table 2 Schedule of Events on page 32 of the Protocol;<br> Secondary end point(s): Effectiveness Endpoints<br> • Worst Itching Intensity NRS<br> • Sleep Quality<br> • 5D-Itch<br> • Skindex-10<br> • EQ-5D-5L-P<br> Additional Endpoints<br> • Missed dialysis visits<br> • Hospitalizations<br> • Incidence of infections<br>

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