Uremic PruritusPhase 2/3NCT02858726

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

A Phase 2/3 study testing CR845 0.5 mcg/kg, CR845 1 mcg/kg and CR845 1.5mcg/kg in people with Uremic Pruritus, run by Cara Therapeutics, Inc. at 29 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Uremic Pruritus
What is being tested?: CR845 0.5 mcg/kg, CR845 1 mcg/kg and CR845 1.5mcg/kg
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 226 participants
Where: 29 sitesUnited States
Study dates: Jun 2016to 14 Mar 2017
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Willing and able to provide written informed consent prior to participating in this study;
Able to communicate clearly with the Investigator and staff, able to read, complete questionnaires, and understand the study procedures;
Males or females 18 years of age or older;
ESRD patients who have been on hemodialysis 3 times per week for at least 3 months prior to the start of Screening;
Women of child-bearing potential must have a negative serum pregnancy test and agree to practice an acceptable form of birth control for the duration of the study
Male patients that are not biologically or surgically sterile must agree to practice an acceptable from of birth control for the duration of the study

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Weigh between 88.2 lb (40.0 kg) and 297.6 lb (135.0 kg).
Patient must self-report pruritus in the month prior to screening.
If patient is receiving treatment for itch, this treatment must be stable prior to screening and during treatment period.
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;
Patient who self-categorize as moderate-to-severe itch.

Who cannot join

Known to be non-compliant with dialysis treatment (i.e., has missed more than 2 dialysis sessions in the past 2 months because of non-compliance);
Anticipated to receive a kidney transplant during the study;
Known history of allergic reaction to opiates, such as hives
Known or suspected history of alcohol, narcotic, or other drug abuse or dependence within 12 months prior to Screening;
Patient has any clinically relevant acute or chronic medical or neuropsychiatric condition which, in the opinion of the Investigator, would pose undue risk to the patient, would impede completion of the study procedures, or would compromise the validity of the study measurements;
Serum alanine aminotransferase or aspartate aminotransferase greater than 2.5 times the reference upper limit of normal (ULN), or total bilirubin greater than 2 times ULN at Screening;

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Received another investigational drug within 30 days prior to the start of Screening or has planned to participate in another clinical trial while enrolled in this study;
Has pruritus probably or definitely attributed to a cause other than ESRD or its complications (e.g., patients with concomitant pruritic dermatological disease or cholestatic liver disease would be excluded). (Note: Patients whose pruritus is attributed to ESRD complications such as hyperparathyroidism, hyperphosphatemia, anemia, or the dialysis procedure or prescription may be enrolled);
Has localized itch restricted to the palms of the hands;
Has pruritus only during the dialysis session (by patient report);
Anticipated to receive opioid antagonists (e.g., naloxone, naltrexone), or opioid mixed agonist-antagonist (e.g., buprenorphine, nalbuphine) from the start of Screening through the end of the Treatment Period;
Used Salvia divinorum or Salvinorin A within 30 days prior to the start of Screening or is anticipated to use it during the study;
Received ultraviolet B treatment within 30 days prior to the start of Screening or anticipated to receive such treatment during the study;
Participated in a previous clinical trial with CR845.

Trial locations and contacts

29 sites in 1 country.

City, postcode or hospital

29 sites in 1 country

United States29 sites

Cara Therapetics Investigator Site
Albuquerque, New Mexico, 87109
Cara Therapeutics Study Site
Augusta, Georgia, 30909
Cara Therapeutics Study Site
Bethlehem, Pennsylvania, 18017
Cara Therapeutics Study Site
Chattanooga, Tennessee, 37408
Cara Therapeutics Study Site
College Point, New York, 11385
Cara Therapetics Study Site
Creve Coeur, Missouri, 63141
Cara Therapeutics Study Site
Denver, Colorado, 80218
Cara Therapeutics Study Site
Gallup, New Mexico, 87301
Cara Therapeutics Study Site
Hollywood, Florida, 33024
Cara Therapeutics Study Site
Kansas City, Missouri, 64111
Cara Therapeutics Study Site
Kansas City, Missouri, 64131
Cara Therapetics Study Site
Knoxville, Tennessee, 37920
Cara Therapeutics Investigator Site
Long Beach, California, 90806
Cara Therapeutics Study Site
Meridian, Idaho, 83642
Cara Therapeutics Study Site
Milwaukee, Wisconsin, 53226
Cara Therapeutics Investigator Site
Mineola, New York, 11501
Cara Therapeutics Study Site
Northridge, California, 91324
Cara Therapeutics Study Site
Omaha, Nebraska, 68124
Cara Therapeutics Investigator Site
Philadelphia, Pennsylvania, 19140
Cara Therapeutics Investigator Site
Phoenix, Arizona, 85035
Cara Therapeutics Study Site
Pine Bluff, Arkansas, 71603
Cara Therapeutics Study Site
San Antonio, Texas, 78221
Cara Therapeutics Study Site
San Antonio, Texas, 78229
Cara Therapeutics Study Site
San Antonio, Texas, 78251
Cara Therapeutics Study Site
Tampa, Florida, 33614
Cara Therapeutics Study Site
Whittier, California, 90603
Cara Therapeutics Investigator Site
Wilmington, North Carolina, 28401
Cara Therapeutics Study Site
Winston-Salem, North Carolina, 27103
Cara Therapeutics Study Site
Winter Park, Florida, 32789

Other trials in United States

About this study

Official title: A Two-Part, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

2 Part Study: Part A will assess 3 different dosing levels of IV CR845 versus placebo in patient on hemodialysis who have moderate-to-severe itching due to uremic pruritus. Patients will receive either CR845 or placebo after each dialysis session for eight weeks. The safety and efficacy of CR845 will be monitored throughout the study. A sub-group of patients will also have pharmacokinetic assessments completed. Part B of the study will assess one dose of IVCR845 versus placebo for 12 weeks in patients on hemodialysis who have moderate-to-severe itching. The dose of CR845 used in Part B will be based on safety and efficacy found in Part A.

Read the detailed description

This is a two-part study. Patients participating in Part A will be consented and trained on the completion of questionnaires about the severity of itching and overall health. Patients will be required to complete questionnaires during their visits to the dialysis center and also while at home on other days. Results of the screening questionnaires will assess eligibility for the study. Additional laboratory tests and measurements for safety will also be completed during the screening period. Patients meeting all criteria for entry into Part A of the study will be randomized to receive either one of three different doses of CR845 or a placebo. Patients will receive the study drug for eight weeks IV after each hemodialysis treatment (i.e. 3 times per week). Assessments for intensity of itch and safety will also be completed during the 8 week treatment period. When patients have completed treatment, a Follow-up visit will be completed 7 days later.

Patients participating in Part B will be consented and trained on the completion of questionnaires about itching and overall health. Patients will be required to complete questionnaires during their visits to the dialysis center and also while at home on other days. Laboratory tests and measurements for safety will also be completed during the screening period to determine study eligibility. Patients meeting all criteria for entry into Part B of the study will be randomized to receive either CR845 or a placebo. The dose of CR845 used will have been determined based on the safety and efficacy from Part A. Patients will be dosed with either CR845 or placebo for twelve weeks after each hemodialysis treatment (i.e. 3 times per week). Assessments for intensity of itch and safety will be completed during the treatment period also. When patients have completed treatment, a Follow-up visit will be completed 7 days later.

Conditions: Uremic Pruritus
Being tested: CR845 0.5 mcg/kg, CR845 1 mcg/kg, CR845 1.5mcg/kg, Placebo
Keywords: Hemodialysis, CR845, Kappa opioid, Anti-itch, difelikefalin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CR845 0.5 mcg/kgDrug
Also called CR845
IV medication delivered three times/week
CR845 1 mcg/kgDrug
Also called CR845
IV medication delivered three times/week
CR845 1.5mcg/kgDrug
Also called CR845
IV medication delivered three times/week
PlaceboDrug
IV medication delivered three times/week

Study groups in NCT02858726
Study group	Role	What they receive
CR845 0.5mcg/kg	Experimental	Part A of study: IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week) Receives: Drug: CR845 0.5 mcg/kg
CR845 1 mcg/kg	Experimental	Part A of study: IV CR845 1 mcg/kg administered after each dialysis session (3 times/week) Receives: Drug: CR845 1 mcg/kg
CR845 1.5mcg/kg	Experimental	Part A of study: IV CR845 1.5 mcg/kg administered after each dialysis session (3 times/week) Receives: Drug: CR845 1.5mcg/kg
Placebo	Placebo comparator	Part A of study: IV Placebo administered after each dialysis session (3 times/week) Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score During Week 8
Intensity of itch was measured using a numerical rating scale (NRS) used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". Higher scores meant worse itch intensity.
Measured: Baseline, Week 8

Secondary outcomes (1)

Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in Total Skindex-10 Scale Score at the End of Week 8
The Skindex-10 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. A lower total score represents better quality of life. The minimum score is 0 and the maximum score is 60 (or total score can range from 0 to 60) with a higher score meaning a worse quality of life.
Measured: Baseline, Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 201614 Mar 2017

First posted8 Aug 2016 (estimated)
Study startJun 2016
Primary completion14 Mar 2017
Study completion14 Mar 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Uremic PruritusStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 226 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02858726
Sponsor's protocol ID: CR845-CLIN2101
Status last verified: Jul 2020
First submitted: 29 Jul 2016
Last updated: 29 Jul 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Undecided

Publications

Hercz D, Jiang SH, Webster AC. Interventions for itch in people with advanced chronic kidney disease. Cochrane Database Syst Rev. 2020 Dec 7;12(12):CD011393. doi: 10.1002/14651858.CD011393.pub2.
PubMed 33283264

Study at a glance

From the registry record, last updated by the sponsor on 29 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Two-Part, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
ClinicalTrials.gov ID: NCT02858726
Acronym / sponsor ID: CR845-CLIN2101
Conditions: Uremic Pruritus
Keywords: Hemodialysis, CR845, Kappa opioid, Anti-itch, difelikefalin
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 226 participants (actual)
Lead sponsor: Cara Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: Jun 2016
Primary completion: 14 Mar 2017 (actual)
Study completion: 14 Mar 2017 (actual)
First posted: 8 Aug 2016 (estimated)
Results: Posted 29 Jul 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
CR845 0.5mcg/kg	Experimental	Drug: CR845 0.5 mcg/kgPart A of study: IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)
CR845 1 mcg/kg	Experimental	Drug: CR845 1 mcg/kgPart A of study: IV CR845 1 mcg/kg administered after each dialysis session (3 times/week)
CR845 1.5mcg/kg	Experimental	Drug: CR845 1.5mcg/kgPart A of study: IV CR845 1.5 mcg/kg administered after each dialysis session (3 times/week)
Placebo	Placebo comparator	Drug: PlaceboPart A of study: IV Placebo administered after each dialysis session (3 times/week)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Willing and able to provide written informed consent prior to participating in this study;
Able to communicate clearly with the Investigator and staff, able to read, complete questionnaires, and understand the study procedures;
Males or females 18 years of age or older;
ESRD patients who have been on hemodialysis 3 times per week for at least 3 months prior to the start of Screening;
Women of child-bearing potential must have a negative serum pregnancy test and agree to practice an acceptable form of birth control for the duration of the study

Key exclusion criteria (14 listed)

Known to be non-compliant with dialysis treatment (i.e., has missed more than 2 dialysis sessions in the past 2 months because of non-compliance);
Anticipated to receive a kidney transplant during the study;
Known history of allergic reaction to opiates, such as hives
Known or suspected history of alcohol, narcotic, or other drug abuse or dependence within 12 months prior to Screening;
Patient has any clinically relevant acute or chronic medical or neuropsychiatric condition which, in the opinion of the Investigator, would pose undue risk to the patient, would impede completion of the study procedures, or would compromise the validity of the study measurements;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CR845 0.5 mcg/kgAlso: CR845IV medication delivered three times/week	Drug	CR845 0.5mcg/kg
CR845 1 mcg/kgAlso: CR845IV medication delivered three times/week	Drug	CR845 1 mcg/kg
CR845 1.5mcg/kgAlso: CR845IV medication delivered three times/week	Drug	CR845 1.5mcg/kg
PlaceboIV medication delivered three times/week	Drug	Placebo

Primary outcome

Change From Baseline in the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score During Week 8
Time frame: Baseline, Week 8
Intensity of itch was measured using a numerical rating scale (NRS) used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". Higher scores meant worse itch intensity.

1 secondary outcome

Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in Total Skindex-10 Scale Score at the End of Week 8
Time frame: Baseline, Week 8

Results and safety

Results posted to the registry on 29 Jul 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CR845 0.5mcg/kg	44	39
CR845 1 mcg/kg	42	35
CR845 1.5mcg/kg	44	33
Placebo	45	42

Primary outcome: Change From Baseline in the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score During Week 8

Time frame: Baseline, Week 8. Least squares mean (Standard Error). Unit: score on a scale

Measure	CR845 0.5mcg/kg n = 44	CR845 1 mcg/kg n = 41	CR845 1.5mcg/kg n = 44	Placebo n = 45
Value	-3.8 (0.4)	-2.8 (0.4)	-3.2 (0.4)	-1.9 (0.4)

CR845 0.5mcg/kg vs Placebo: Mean Difference (Final Values): -1.8 (95% CI -2.8 to -0.8), p <0.001, Mixed Models Analysis
CR845 1 mcg/kg vs Placebo: Mean Difference (Final Values): -0.8 (95% CI -1.9 to 0.2), p = 0.107, Mixed Models Analysis
CR845 1.5mcg/kg vs Placebo: Median Difference (Final Values): -1.2 (95% CI -2.3 to -0.2), p = 0.019, Mixed Models Analysis

1 secondary outcome is reported in the full results.

Adverse events

Time frame: The period of adverse event reporting started after the signing of the ICF through the study follow-up visit or early termination visit (or 7 days after the last dose if no early termination visit was conducted).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CR845 0.5mcg/kg	10 of 44 (22.7%)	22 of 44 (50%)	1 of 44
CR845 1 mcg/kg	6 of 41 (14.6%)	16 of 41 (39%)	0 of 41
CR845 1.5mcg/kg	11 of 44 (25%)	18 of 44 (40.9%)	2 of 44
Placebo	4 of 45 (8.9%)	3 of 45 (6.7%)	1 of 45

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33283264Hercz D, Jiang SH, Webster AC. Interventions for itch in people with advanced chronic kidney disease. Cochrane Database Syst Rev. 2020 Dec 7;12(12):CD011393. doi: 10.1002/14651858.CD011393.pub2.
Individual participant dataSharing planned: Undecided

Related trials for Uremic Pruritus

Active, not recruitingObservational study
Cardiovascular and Bone Mineral Markers in Dialysis Patients and Healthy Controls
End-Stage Kidney Disease (ESKD), Hemodialysis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Frederique Menzaghi, PhD study director

Cara Therapeutics

29 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing CR845 0.5 mcg/kg, CR845 1 mcg/kg and CR845 1.5mcg/kg in people with Uremic Pruritus, run by Cara Therapeutics, Inc. at 29 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score During Week 8 (time frame: Baseline, Week 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02858726, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2020.

Trial summary

Key requirements

Who may be able to join

Who cannot join

Trial locations and contacts

About this study

What participants receive

What is being measured

Timeline

Resources

More details

Publications

Study at a glance

Clinical summary

Study design

Who may qualify

Key inclusion criteria (11 listed)

Key exclusion criteria (14 listed)

Interventions

Primary outcome

Results and safety

Participant flow

Primary outcome: Change From Baseline in the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score During Week 8

Adverse events

Research links

Related trials for Uremic Pruritus

Cardiovascular and Bone Mineral Markers in Dialysis Patients and Healthy Controls

Referral and contact

Questions about this trial

Participant flow

Primary outcome: Change From Baseline in the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score During Week 8

Adverse events