Uremic PruritusPhase 3NCT03998163
CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
A Phase 3 study testing CR845 0.5 mcg/kg in people with Uremic Pruritus, run by Cara Therapeutics, Inc. at 47 sites in 4 countries.
Trial summary
This is a multicenter, open-label study to evaluate the safety and effectiveness of intravenous (IV) CR845 at a dose of 0.5 mcg/kg administered after each dialysis session. The study includes an up to 12-week Treatment Period. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Uremic Pruritus
- What is being tested?
- CR845 0.5 mcg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 222 participants
- Where
- 47 sitesin 4 countries
- Study dates
- 6 May 2019to 6 Mar 2020
- Phase
- Phase 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 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:
- 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 Treatment:
- Has completed at least 3 Worst Itching Intensity NRS questionnaires from the start of the Run-in Period up to and including the pre-dose assessment on Day 1;
Who cannot join
- A patient will be excluded from 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;
- New or change of prescription for opioids, gabapentin, or pregabalin within 14 days prior to screening;
- 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;
Show all 9Show fewer
- Has pruritus only during the dialysis session (by patient report);
- Is receiving ongoing ultraviolet B treatment and/or anticipates receiving such treatment during the study;
- Participated in a previous clinical study with CR845.
Trial locations and contacts
47 sites in 4 countries.
47 sites in 4 countries
United States33 sites
Cara Therapeutics Study Site
Albany, Georgia, 31701
Cara Therapeutics Study Site
Austin, Texas, 78751
Cara Therapeutics Study Site
Boston, Massachusetts, 02111
Cara Therapeutics Study Site
Coral Gables, Florida, 33134
Cara Therapeutics Study Site
Denver, Colorado, 80230
Cara Therapeutics Study Site
Duncanville, Texas, 75137
Cara Therapeutics Study Site
Escondido, California, 92025
Cara Therapeutics Study Site
Fort Lauderdale, Florida, 33308
Cara Therapeutics Study Site
Great Neck, New York, 11021
Cara Therapeutics Study Site
Greenville, Texas, 75402
Cara Therapeutics Study Site
Hollywood, Florida, 33024
Cara Therapeutics Study Site
Kansas City, Missouri, 64131
Cara Therapeutics Study Site
Knoxville, Tennessee, 37920
Cara Therapeutics Study Site
Las Vegas, Nevada, 89106
Cara Therapeutics Study Site 2
Las Vegas, Nevada, 89128
Cara Therapeutics Study Site
Mansfield, Texas, 76063
Cara Therapeutics Study Site
Mesquite, Texas, 75080
Cara Therapeutics Study Site
Miami, Florida, 33169
Cara Therapeutics Study Site
Middlebury, Connecticut, 06762
Cara Therapeutics Study Site
Minneapolis, Minnesota, 55404
Cara Therapeutics Study Site
Norwich, Connecticut, 06382
Cara Therapeutics Study Site
Philadelphia, Pennsylvania, 19140
Cara Therapeutics Study Site
Riverside, California, 92505
Cara Therapeutics Study Site
Roseville, Michigan, 48066
Cara Therapeutics Study Site 2
San Antonio, Texas, 78221
Cara Therapeutics Study Site
San Antonio, Texas, 78251
Cara Therapeutics Study Site 3
San Antonio, Texas, 78258
Cara Therapeutics Study Site
San Diego, California, 92111
Cara Therapeutics Study Site
Spartanburg, South Carolina, 29302
Cara Therapeutics Study Site 2
Tampa, Florida, 33614
Cara Therapeutics Study Site
Tampa, Florida, 33614
Cara Therapeutics Study Site
Temple, Texas, 76502
Cara Therapeutics Study Site
Victorville, California, 92395
Hungary7 sites
Cara Therapeutics Study Site 2
Budapest
Cara Therapeutics Study Site
Budapest
Cara Therapeutics Study Site
Dunaújváros
Cara Therapeutics Study Site
Kaposvár
Cara Therapeutics Study Site
Kistarcsa
Cara Therapeutics Study Site
Nyíregyháza
Cara Therapeutics Study Site
Szombathely
Czechia4 sites
Cara Therapeutics Study Site
Havlíčkův Brod
Cara Therapeutics Study Site
Nové Město na Moravě
Cara Therapeutics Study Site
Prague
Cara Therapeutics Study Site
Sokolov
Poland3 sites
Cara Therapeutics Study Site
Ostrołęka
Cara Therapeutics Study Site
Radom
Cara Therapeutics Study Site
Sochaczew
About this study
Official title: An Open-Label, Multicenter Study to Evaluate the Safety and Effectiveness of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
This is a multicenter, open-label study to evaluate the safety and effectiveness of intravenous (IV) CR845 at a dose of 0.5 mcg/kg administered after each dialysis session. The study includes an up to 12-week Treatment Period.
Read the detailed description
Screening Period: The Screening Period includes a Screening Visit and a Run-In Period. Informed consent will be obtained prior to performing any study-specific procedures. The Screening Visit will occur within 21 days prior to the start of the Run-in Period. Patients will start the Run-in Period during the week prior to Treatment Period to complete eligibility verification.
Treatment Period: All scheduled study visits during the Treatment Period will be conducted on dialysis days. Patients will be administered CR845 as an IV bolus after the end of their dialysis during a Treatment Period of up to 12 weeks so that each patient will receive CR845 3 times weekly for a total of up to 36 doses. End of treatment (EOT) is defined as the first day of dialysis following the last dose of drug. The EOT procedures will be conducted on the dialysis visit following the last dose of study drug.
Follow-up Visit: A final safety Follow up Visit will be conducted 7-10 days after the EOT/Early Termination Visit.
- Conditions
- Uremic Pruritus
- Being tested
- CR845 0.5 mcg/kg
- Keywords
- Hemodialysis, Pruritus, Uremic Pruritus, Dialysis, CR845, Chronic Itch, CKD, CKD-associated pruritus, CKD-aP, ESRD (end stage renal disease), difelikefalin, Itch, Itching, KALM, Chronic Kidney Disease, Kidney failure, chronic, Kidney dysfunction, Generalized pruritus
- Medical subject headings
- Pruritus, Renal Insufficiency, Chronic, Kidney Failure, Chronic
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, Difelikefalin
IV CR845 0.5 mcg/kg administered three times/week
| Study group | Role | What they receive |
|---|---|---|
| CR845 0.5mcg/kg | Experimental | IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week) Receives: Drug: CR845 0.5 mcg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With AEs.
Assessed by monitoring of adverse events.
Measured: Up to Follow-Up Visit (Week 13-14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2019
- Study start6 May 2019
- Primary completion26 Feb 2020
- Study completion6 Mar 2020
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 (5)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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 222 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cara Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frédérique Menzaghi, PhD, Study director, Cara Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03998163
- Sponsor's protocol ID
- CR845-CLIN3105
- Status last verified
- Sep 2021
- First submitted
- 7 May 2019
- Last updated
- 15 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fishbane SN, Block GA, Evenepoel P, Budden J, Morin I, Menzaghi F, Wen W, Lerma EV. Pruritus Severity and Serum Phosphate in CKD: A Post Hoc Analysis of Difelikefalin Studies. Kidney360. 2024 Sep 1;5(9):1270-1280. doi: 10.34067/KID.0000000000000520. Epub 2024 Jul 22.
PubMed 39037824Fotheringham J, Guest J, Latus J, Lerma E, Morin I, Schaufler T, Soro M, Stander S, Zeig S. Impact of Difelikefalin on the Health-Related Quality of Life of Haemodialysis Patients with Moderate-To-Severe Chronic Kidney Disease-Associated Pruritus: A Single-Arm Intervention Trial. Patient. 2024 Mar;17(2):203-213. doi: 10.1007/s40271-023-00668-1. Epub 2024 Jan 9.
PubMed 38196014Weiner DE, Schaufler T, McCafferty K, Kalantar-Zadeh K, Germain M, Ruessmann D, Morin I, Menzaghi F, Wen W, Stander S. Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis. Nephrol Dial Transplant. 2024 Jun 28;39(7):1125-1137. doi: 10.1093/ndt/gfad245.
PubMed 37968132Weiner DE, Vervloet MG, Walpen S, Schaufler T, Munera C, Menzaghi F, Wen W, Bhaduri S, Germain MJ; trial investigators. Safety and Effectiveness of Difelikefalin in Patients With Moderate-to-Severe Pruritus Undergoing Hemodialysis: An Open-Label, Multicenter Study. Kidney Med. 2022 Aug 24;4(10):100542. doi: 10.1016/j.xkme.2022.100542. eCollection 2022 Oct.
PubMed 36185706Fishbane S, Wen W, Munera C, Lin R, Bagal S, McCafferty K, Menzaghi F, Goncalves J. Safety and Tolerability of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis From the Phase 3 Clinical Trial Program. Kidney Med. 2022 Jun 28;4(8):100513. doi: 10.1016/j.xkme.2022.100513. eCollection 2022 Aug.
PubMed 36039153
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multicenter Study to Evaluate the Safety and Effectiveness of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
- ClinicalTrials.gov ID
- NCT03998163
- Acronym / sponsor ID
- CR845-CLIN3105
- Conditions
- Uremic Pruritus
- Keywords
- Hemodialysis, Pruritus, Uremic Pruritus, Dialysis, CR845, Chronic Itch, CKD, CKD-associated pruritus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 222 participants (actual)
- Lead sponsor
- Cara Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 May 2019 (actual)
- Primary completion
- 26 Feb 2020 (actual)
- Study completion
- 6 Mar 2020 (actual)
- First posted
- 26 Jun 2019 (actual)
- Results
- Posted 15 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, open-label study to evaluate the safety and effectiveness of intravenous (IV) CR845 at a dose of 0.5 mcg/kg administered after each dialysis session. The study includes an up to 12-week Treatment Period.
Detailed description
Screening Period: The Screening Period includes a Screening Visit and a Run-In Period. Informed consent will be obtained prior to performing any study-specific procedures. The Screening Visit will occur within 21 days prior to the start of the Run-in Period. Patients will start the Run-in Period during the week prior to Treatment Period to complete eligibility verification.
Treatment Period: All scheduled study visits during the Treatment Period will be conducted on dialysis days. Patients will be administered CR845 as an IV bolus after the end of their dialysis during a Treatment Period of up to 12 weeks so that each patient will receive CR845 3 times weekly for a total of up to 36 doses. End of treatment (EOT) is defined as the first day of dialysis following the last dose of drug. The EOT procedures will be conducted on the dialysis visit following the last dose of study drug.
Follow-up Visit: A final safety Follow up Visit will be conducted 7-10 days after the EOT/Early Termination Visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CR845 0.5mcg/kg | Experimental | Drug: CR845 0.5 mcg/kgIV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 Treatment:
Key exclusion criteria (9 listed)
- 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;
- New or change of prescription for opioids, gabapentin, or pregabalin within 14 days prior to screening;
- 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;
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: CR845, DifelikefalinIV CR845 0.5 mcg/kg administered three times/week | Drug | CR845 0.5mcg/kg |
Primary outcome
Number of Participants With AEs.
Time frame: Up to Follow-Up Visit (Week 13-14)
Assessed by monitoring of adverse events.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39037824Fishbane SN, Block GA, Evenepoel P, Budden J, Morin I, Menzaghi F, Wen W, Lerma EV. Pruritus Severity and Serum Phosphate in CKD: A Post Hoc Analysis of Difelikefalin Studies. Kidney360. 2024 Sep 1;5(9):1270-1280. doi: 10.34067/KID.0000000000000520. Epub 2024 Jul 22.
- Derived from this study: PubMed 38196014Fotheringham J, Guest J, Latus J, Lerma E, Morin I, Schaufler T, Soro M, Stander S, Zeig S. Impact of Difelikefalin on the Health-Related Quality of Life of Haemodialysis Patients with Moderate-To-Severe Chronic Kidney Disease-Associated Pruritus: A Single-Arm Intervention Trial. Patient. 2024 Mar;17(2):203-213. doi: 10.1007/s40271-023-00668-1. Epub 2024 Jan 9.
- Derived from this study: PubMed 37968132Weiner DE, Schaufler T, McCafferty K, Kalantar-Zadeh K, Germain M, Ruessmann D, Morin I, Menzaghi F, Wen W, Stander S. Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis. Nephrol Dial Transplant. 2024 Jun 28;39(7):1125-1137. doi: 10.1093/ndt/gfad245.
- Derived from this study: PubMed 36185706Weiner DE, Vervloet MG, Walpen S, Schaufler T, Munera C, Menzaghi F, Wen W, Bhaduri S, Germain MJ; trial investigators. Safety and Effectiveness of Difelikefalin in Patients With Moderate-to-Severe Pruritus Undergoing Hemodialysis: An Open-Label, Multicenter Study. Kidney Med. 2022 Aug 24;4(10):100542. doi: 10.1016/j.xkme.2022.100542. eCollection 2022 Oct.
- Derived from this study: PubMed 36039153Fishbane S, Wen W, Munera C, Lin R, Bagal S, McCafferty K, Menzaghi F, Goncalves J. Safety and Tolerability of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis From the Phase 3 Clinical Trial Program. Kidney Med. 2022 Jun 28;4(8):100513. doi: 10.1016/j.xkme.2022.100513. eCollection 2022 Aug.
- Individual participant dataSharing planned: No
Related trials for Uremic Pruritus
Active, not recruitingObservational study
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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.
Frédérique Menzaghi, PhD study director
Cara Therapeutics
47 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CR845 0.5 mcg/kg in people with Uremic Pruritus, run by Cara Therapeutics, Inc. at 47 sites in 4 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 5 inclusion and 9 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 15 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in United States, Hungary, Czechia, Poland. 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. 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?
Yes. Results are posted in the registry (first posted 15 Oct 2021). 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?
Number of Participants With AEs. (time frame: Up to Follow-Up Visit (Week 13-14)). 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 NCT03998163, which also lists 5 linked publications.
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 15 Oct 2021.