Chronic Kidney DiseasesPhase 3NCT05356403

CR845-310302: A Study to Evaluate the Safety and Efficacy of Difelikefalin in Advanced Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

A Phase 3 study testing Difelikefalin 1 mg Oral Tablet in people with Chronic Kidney Diseases and Pruritus, run by Cara Therapeutics, Inc. at 75 sites in 13 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Chronic Kidney Diseases, Pruritus
What is being tested?: Difelikefalin 1 mg Oral Tablet
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 105 participants
Where: 75 sitesin 13 countries
Study dates: 26 Aug 2022to 26 Feb 2024
Phase: Phase 3
Are there results?: None posted in the registry

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 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

To be eligible for inclusion into the study, a patient must meet the following criteria:
Advanced stage 4 and 5 CKD and end stage renal disease on hemodialysis
Subject self-reports experiencing at least near-daily (eg, most days of a week) pruritus for at least 6 months prior to screening.
Inadequate response to current or prior treatments (including emollients/moisturizers, topical medications, or systemic treatments) for pruritus prior to screening.
Prior to randomization on Day 1 of Treatment Period 1:
Has recorded at least 4 WI-NRS scores during the 7-day Run-in Period; and
Has a mean baseline WI-NRS score ≥ 5, defined as the average of all non-missing scores reported during the 7-day Run-in Period.

Who cannot join

A patient will be excluded from the study if any of the following criteria are met:
Scheduled to receive a renal replacement therapy (dialysis or kidney transplant) during the study.
Has a concomitant disease, significant medical condition or physical/laboratory/ECG/vital signs abnormality that, in the opinion of the investigator, puts the subject at undue risk or interferes with interpretation of study results, impedes completion of the study procedures, or compromises the validity of the study measurements.
New or change of treatment received for itch, including antihistamines and corticosteroids (oral, intravenous, or topical), within 14 days prior to the start of run-in.

Trial locations and contacts

75 sites in 13 countries.

Country

City, postcode or hospital

75 sites in 13 countries

Australia10 sites

Cara Therapeutics Study Site
Adelaide
Cara Therapeutics Study Site
Camperdown
Cara Therapeutics Study Site
Concord
Cara Therapeutics Study Site
Gosford
Cara Therapeutics Study Site
Kogarah
Cara Therapeutics Study Site
Launceston
Cara Therapeutics Study Site
Liverpool
Cara Therapeutics Study Site
Melbourne
Cara Therapeutics Study Site
Saint Albans
Cara Therapeutics Study Site
Westmead

Other trials in Australia

United States9 sites

Cara Therapeutics Study Site
Brunswick, Georgia, 31520
Cara Therapeutics Study Site
Miami, Florida, 33032
Cara Therapeutics Study Site
Miami Lakes, Florida, 33014
Cara Therapeutics Study Site
Miami Lakes, Florida, 33016
Cara Therapeutics Study Site
New York, New York, 10016
Cara Therapeutics Study Site
Northridge, California, 91324
Cara Therapeutics Study Site
Orangeburg, South Carolina, 29118
Cara Therapeutics Study Site
Sugar Land, Texas, 77476
Cara Therapeutics Study Site
Weston, Florida, 33331

Other trials in United States

Spain9 sites

Cara Therapeutics Study Site
Almería, 04009
Cara Therapeutics Study Site
Badalona
Cara Therapeutics Study Site
Barcelona
Cara Therapeutics Study Site
Ferrol, 15405
Cara Therapeutics Study Site
Madrid
Cara Therapeutics Study Site
Palma de Mallorca
Cara Therapeutics Study Site 2
Valencia
Cara Therapeutics Study Site
Valencia
Cara Therapeutics Study Site
Vitoria-Gasteiz

Other trials in Spain

Brazil8 sites

Cara Therapeutics Study Site
Belo Horizonte
Cara Therapeutics Study Site
Joinville, 89227-680
Cara Therapeutics Study Site
Salvador
Cara Therapeutics Study Site
São Bernardo do Campo
Cara Therapeutics Study Site
São José do Rio Preto
Cara Therapeutics Study Site
São Paulo, 09090-790
Cara Therapeutics Study Site 2
São Paulo
Cara Therapeutics Study Site
São Paulo

Other trials in Brazil

Poland7 sites

Cara Therapeutics Study Site
Golub-Dobrzyń
Cara Therapeutics Study Site
Katowice
Cara Therapeutics Study Site 2
Krakow
Cara Therapeutics Study Site
Krakow
Cara Therapeutics Study Site
Lodz
Cara Therapeutics Study Site
Szczecin
Cara Therapeutics Study Site
Wroclaw

Other trials in Poland

Argentina6 sites

Cara Therapeutics Study Site
Ciudad Autonoma de Buenos Aire, C1425DES
Cara Therapeutics Study Site
Corrientes, W3400AMZ
Cara Therapeutics Study Site
Lanus, B1824KAJ
Cara Therapeutics Study Site
Mar del Plata
Cara Therapeutics Study Site
San Nicolás, 2900
Cara Therapeutics Study Site
Sarandí, 1872

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South Korea5 sites

Cara Therapeutics Study Site
Daegu
Cara Therapeutics Study Site 2
Goyang-si
Cara Therapeutics Study Site
Goyang-si
Cara Therapeutics Study Site
Seoul, 03080
Cara Therapeutics Study Site
Seoul

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Bulgaria4 sites

Cara Therapeutics Study Site
Dobrich
Cara Therapeutics Study Site
Gabrovo
Cara Therapeutics Study Site
Montana
Cara Therapeutics Study Site
Plovdiv

Other trials in Bulgaria

Hungary4 sites

Cara Therapeutics Study Site
Baja
Cara Therapeutics Study Site
Budapest
Cara Therapeutics Study Site
Kistarcsa
Cara Therapeutics Study Site
Pécs

Other trials in Hungary

Italy4 sites

Cara Therapeutics Study Site
Florence
Cara Therapeutics Study Site
Modena, 41124
Cara Therapeutics Study Site
Pavia, 27100
Cara Therapeutics Study Site
Roma

Other trials in Italy

Mexico4 sites

Cara Therapeutics Study Site
Aguas Calientes
Cara Therapeutics Study Site
Durango
Cara Therapeutics Study Site
Guadalajara
Cara Therapeutics Study Site
Mérida

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Romania3 sites

Cara Therapeutics Study Site
Bucharest
Cara Therapeutics Study Site
Oradea
Cara Therapeutics Study Site
Timișoara

Other trials in Romania

Germany2 sites

Cara Therapeutics Study Site
Heilbronn
Cara Therapeutics Study Site
Kaiserslautern

Other trials in Germany

About this study

Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled 12-Week Study to Evaluate the Safety and Efficacy of Oral Difelikefalin in Advanced Chronic Kidney Disease Subjects With Moderate-to-Severe Pruritus With an up to 52-Week Long-term Extension

This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of oral difelikefalin administered as a 1 mg tablet once daily compared to placebo in reducing the intensity of itch in advanced chronic kidney disease (CKD) patients with moderate-to-severe pruritus. This study is comprised of an Efficacy Assessment Phase and a Long-term Extension Phase. The Efficacy Assessment Phase includes a double-blind 12-week Treatment Period (Treatment Period 1), and the Long-term Extension Phase includes a double-blind Treatment Period (Treatment Period 2) of up to 52 weeks.

Read the detailed description

This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week double-blind Efficacy Assessment Phase (Treatment Period 1), a double-blind Long-term Extension Phase (Treatment Period 2) of up to 52 weeks, and a Follow-up Visit (7 to 10 days after the End of Treatment (EOT)/Early Termination (ET) Visit).

If patients continue to meet all inclusion and no exclusion criteria at the end of the 7-day Run-in Period, they will be randomized in a 1:1 ratio to receive once daily oral difelikefalin tablets at a dose of 1 mg or placebo for 12 weeks. Subjects will be stratified according to their use or nonuse of medications to treat pruritus prior to randomization as well as the presence or absence of specific medical conditions. During the Long-term Extension Phase, patients will be re-randomized on Day 1 of Treatment Period 2 to receive either oral difelikefalin 1 mg or placebo, once daily for up to an additional 52 weeks. A final safety Follow-up Visit will be conducted 7 to 10 days after the EOT/ET.

Informed consent will be obtained prior to performing any study-specific procedures. Screening will occur within 7 to 28 days prior to randomization to assess eligibility.

Conditions: Chronic Kidney Diseases, Pruritus
Being tested: Difelikefalin 1 mg Oral Tablet, Placebo Oral Tablet
Keywords: difelikefalin, CR845, Pruritus, Chronic Itch, Itch, Itching, uremic pruritus, CKD, CKD-aP, CKD-associated pruritus, Chronic Kidney Disease, Kidney dysfunction, Generalized pruritus, Hemodialysis, Dialysis, ESRD (end stage renal disease), Kidney failure, chronic
Medical subject headings: Renal Insufficiency, Chronic, Pruritus, Kidney Failure, Chronic

What participants receive

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

Difelikefalin 1 mg Oral TabletDrug
Also called CR845
Difelikefalin 1 mg medication taken orally 1 time/day
Placebo Oral TabletDrug
Placebo tablet taken orally 1 time/day

Study groups in NCT05356403
Study group	Role	What they receive
Difelikefalin 1 mg Oral Tablet	Experimental	Patients receive oral difelikefalin 1 mg once daily Receives: Drug: Difelikefalin 1 mg Oral Tablet
Placebo Oral Tablet	Placebo comparator	Patients receive oral placebo once daily Receives: Drug: Placebo Oral Tablet

What is being measured

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

Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS score at Week 12 of Treatment Period 1
Intensity of itch will be measured using an 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".
Measured: Week 12 of Treatment Period 1

Secondary outcomes (4)

Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the WI-NRS at Week 8 of Treatment Period 1.
Intensity of itch will be measured using an 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".
Measured: Week 8 of Treatment Period 1
Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the WI-NRS at Week 4 of Treatment Period 1.
Intensity of itch will be measured using an 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".
Measured: Week 4 of Treatment Period 1
Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects who are "complete itch responders" defined as subjects with ≥ 70% of the non-missing 24-hour WI-NRS scores equal to 0 or 1 at Week 12 of Treatment Period 1.
Intensity of itch will be measured using an 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".
Measured: Week 12 of Treatment Period 1
Efficacy Assessment Phase (Treatment Period 1): Change from baseline in Sleep Quality Questionnaire score at the end of Week 12 of Treatment Period 1.
Sleep Quality will be measured using an NRS used to indicate how much itch has interfered with sleep during the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "did not interfere" and "10" represents "completely interfered".
Measured: Week 12 of Treatment Period 1

Timeline

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

26 Aug 202226 Feb 2024

First posted2 May 2022
Study start26 Aug 2022
Primary completion26 Feb 2024
Study completion26 Feb 2024

Why it stopped: Corporate decision to discontinue work in advanced chronic kidney disease

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Chronic Kidney DiseasesStudies 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized, double-blind, placebo controlled study
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 105 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05356403
Sponsor's protocol ID: CR845-310302
Status last verified: May 2024
First submitted: 18 Apr 2022
Last updated: 7 May 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled 12-Week Study to Evaluate the Safety and Efficacy of Oral Difelikefalin in Advanced Chronic Kidney Disease Subjects With Moderate-to-Severe Pruritus With an up to 52-Week Long-term Extension
ClinicalTrials.gov ID: NCT05356403
Acronym / sponsor ID: CR845-310302
Conditions: Chronic Kidney Diseases, Pruritus
Keywords: difelikefalin, CR845, Pruritus, Chronic Itch, Itch, Itching, uremic pruritus, CKD
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Corporate decision to discontinue work in advanced chronic kidney disease
Enrolment: 105 participants (actual)
Lead sponsor: Cara Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 26 Aug 2022 (actual)
Primary completion: 26 Feb 2024 (actual)
Study completion: 26 Feb 2024 (actual)
First posted: 2 May 2022 (actual)
Results: Not posted in the source record

Clinical summary

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

Detailed description

Informed consent will be obtained prior to performing any study-specific procedures. Screening will occur within 7 to 28 days prior to randomization to assess eligibility.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2
Model description: Randomized, double-blind, placebo controlled study

Arm	Type	Receives
Difelikefalin 1 mg Oral Tablet	Experimental	Drug: Difelikefalin 1 mg Oral TabletPatients receive oral difelikefalin 1 mg once daily
Placebo Oral Tablet	Placebo comparator	Drug: Placebo Oral TabletPatients receive oral placebo once daily

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Advanced stage 4 and 5 CKD and end stage renal disease on hemodialysis
Subject self-reports experiencing at least near-daily (eg, most days of a week) pruritus for at least 6 months prior to screening.
Inadequate response to current or prior treatments (including emollients/moisturizers, topical medications, or systemic treatments) for pruritus prior to screening.
Has recorded at least 4 WI-NRS scores during the 7-day Run-in Period; and
Has a mean baseline WI-NRS score ≥ 5, defined as the average of all non-missing scores reported during the 7-day Run-in Period.

Key exclusion criteria (4 listed)

Scheduled to receive a renal replacement therapy (dialysis or kidney transplant) during the study.
Has a concomitant disease, significant medical condition or physical/laboratory/ECG/vital signs abnormality that, in the opinion of the investigator, puts the subject at undue risk or interferes with interpretation of study results, impedes completion of the study procedures, or compromises the validity of the study measurements.
New or change of treatment received for itch, including antihistamines and corticosteroids (oral, intravenous, or topical), within 14 days prior to the start of run-in.

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
Difelikefalin 1 mg Oral TabletAlso: CR845Difelikefalin 1 mg medication taken orally 1 time/day	Drug	Difelikefalin 1 mg Oral Tablet
Placebo Oral TabletPlacebo tablet taken orally 1 time/day	Drug	Placebo Oral Tablet

Primary outcome

Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS score at Week 12 of Treatment Period 1
Time frame: Week 12 of Treatment Period 1
Intensity of itch will be measured using an 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".

4 secondary outcomes

Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the WI-NRS at Week 8 of Treatment Period 1.
Time frame: Week 8 of Treatment Period 1
Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the WI-NRS at Week 4 of Treatment Period 1.
Time frame: Week 4 of Treatment Period 1
Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects who are "complete itch responders" defined as subjects with ≥ 70% of the non-missing 24-hour WI-NRS scores equal to 0 or 1 at Week 12 of Treatment Period 1.
Time frame: Week 12 of Treatment Period 1
Efficacy Assessment Phase (Treatment Period 1): Change from baseline in Sleep Quality Questionnaire score at the end of Week 12 of Treatment Period 1.
Time frame: Week 12 of Treatment Period 1

Results and safety

The study was stopped early (reason given: Corporate decision to discontinue work in advanced chronic kidney disease). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
Individual participant dataSharing planned: No

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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.

Cara Therapeutics, PhD study director

Cara Therapeutics

75 sites in 13 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Difelikefalin 1 mg Oral Tablet in people with Chronic Kidney Diseases and Pruritus, run by Cara Therapeutics, Inc. at 75 sites in 13 countries.

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 7 inclusion and 4 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: stopped early, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 75 sites in Australia, United States, Spain, Brazil, Poland and 8 more countries. 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 phase mean?

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?

The study was stopped early (reason given: Corporate decision to discontinue work in advanced chronic kidney disease). Results are not available in the source record.

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?

Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS score at Week 12 of Treatment Period 1 (time frame: Week 12 of Treatment Period 1). 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 NCT05356403.

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 7 May 2024.