Cholestatic PruritusPhase 2NCT03995212
Study to Evaluate the Safety and Efficacy of Oral CR845 (Difelikefalin) in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus
A Phase 2 study testing CR845 1.0 mg in people with Cholestatic Pruritus, run by Cara Therapeutics, Inc. at 14 sites in United States.
Trial summary
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of twice-daily (BID) oral CR845 1.0 mg in patients with PBC with moderate-to-severe pruritus. The study includes a 16-week Treatment Period. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cholestatic Pruritus
- What is being tested?
- CR845 1.0 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 14 sitesUnited States
- Study dates
- 25 Jun 2019to 29 Jun 2022
- Phase
- Phase 2
- 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 80 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:
- Confirmed diagnosis of PBC;
- If currently taking ursodeoxycholic acid (UDCA), should be on stable dose for >12 weeks prior to screening and plan on continuing to take UDCA throughout the study;
- If previously taking UDCA, should have discontinued its use >12 weeks prior to screening;
- Self-reports experiencing daily or near-daily pruritus during the month prior to screening;
- Prior to randomization has a mean baseline WI-NRS score indicative of moderate to severe pruritus.
Who cannot join
- A patient will be excluded from the study if any of the following criteria are met:
- Presence of Child-Pugh Class C decompensated cirrhosis at screening;
- Itching secondary to biliary obstruction;
- History or presence of hepatocellular carcinoma, hepatic abscess, or acute portal vein thrombosis;
- Current placement on liver transplantation list with anticipated liver transplant during the course of the study or current Model for End-stage Liver Disease (MELD) score ≥15;
- Alanine aminotransferase or aspartate aminotransferase >5 × upper limit of normal at screening, or within 2 months prior to screening;
- Anticipates receiving an opioid antagonist (eg, naloxone, naltrexone) or opioid-mixed agonist-antagonist (eg, buprenorphine, nalbuphine) from the start of screening through the end of the Treatment Period;
- New or change of treatment with antihistamines and corticosteroids (oral, intravenous, or topical), opioids, gabapentin, pregabalin, cholestyramine, rifampicin or fibrates within 14 days prior to screening.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Cara Therapeutics Study Site
Arlington, Texas, 76012
Cara Therapeutics Study Site 2
Boston, Massachusetts, 02114
Cara Therapeutics Study Site
Boston, Massachusetts, 02215
Cara Therapeutics Study Site
Colorado Springs, Colorado, 80907
Cara Therapeutics Study Site
Coronado, California, 92118
Cara Therapeutics Study Site
Indianapolis, Indiana, 46202
Cara Therapeutics Study Site
Miami, Florida, 33136
Cara Therapeutics Study Site
Morgantown, West Virginia, 26506
Cara Therapeutics Study Site
Nashville, Tennessee, 37232
Cara Therapeutics Study Site
New York, New York, 10065
Cara Therapeutics Study Site
Newport News, Virginia, 23606
Cara Therapeutics Study Site
Plantation, Florida, 33322
Cara Therapeutics Study Site
Rialto, California, 92377
Cara Therapeutics Study Site
San Francisco, California, 94114
About this study
Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral CR845 in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of twice-daily (BID) oral CR845 1.0 mg in patients with PBC with moderate-to-severe pruritus. The study includes a 16-week Treatment Period.
Read the detailed description
This study will consist of a Screening Visit, a 7-day Run-in Period, a 16-week Treatment Period, and a Follow-up Visit (approximately 7-10 days after the last dose of study drug). Informed consent will be obtained prior to performing any study-specific procedures.
The Screening Visit will occur within 7 to 28 days prior to randomization to assess eligibility.
Day 1 of the Treatment Period will be defined as the day of the administration of the first dose of study drug. 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 either placebo or CR845 tablets at a dose of 1.0 mg orally BID for 16 weeks.
- Conditions
- Cholestatic Pruritus
- Being tested
- CR845 1.0 mg, Placebo
- Keywords
- Primary Biliary Cholangitis, Pruritus, CR845, Chronic Itch, difelikefalin, Itch, Itching, Generalized pruritus
- Medical subject headings
- Liver Cirrhosis, Biliary, Pruritus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CR845 1.0 mgDrug
Also called CR845, Difelikefalin
Oral CR845 1.0 mg administered twice daily
PlaceboDrug
Oral Placebo administered twice daily
| Study group | Role | What they receive |
|---|---|---|
| CR845 1.0 mg | Active comparator | Oral CR845 1.0 mg tablet administered twice daily Receives: Drug: CR845 1.0 mg |
| Placebo | Placebo comparator | Oral placebo tablet administered twice daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to Week 16 with respect to the weekly mean of the daily 24-hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score.
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: Baseline, Week 16
Secondary outcomes (3)
Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in total Skindex-10 Scale score
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.
Measured: Baseline, Week 16
Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in 5-D Itch Scale score
The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the degree, duration of itch/day, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. A lower total score represents better quality of life.
Measured: Baseline, Week 16
Reduction of itch intensity as assessed by the proportion of patients achieving an improvement from baseline ≥3 points with respect to the weekly mean of the daily 24-hour WI-NRS score at Week 16
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 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2019
- Study start25 Jun 2019
- Primary completion29 Jun 2022
- Study completion29 Jun 2022
Why it stopped: Slow enrollment due primarily to Covid-19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cholestatic 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 14 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
- NCT03995212
- Sponsor's protocol ID
- CR845-210401
- Status last verified
- Jun 2023
- First submitted
- 19 Jun 2019
- Last updated
- 3 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral CR845 in Patients With Primary Biliary Cholangitis (PBC) and Moderate-to-Severe Pruritus
- ClinicalTrials.gov ID
- NCT03995212
- Acronym / sponsor ID
- CR845-210401
- Conditions
- Cholestatic Pruritus
- Keywords
- Primary Biliary Cholangitis, Pruritus, CR845, Chronic Itch, difelikefalin, Itch, Itching, Generalized pruritus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment due primarily to Covid-19
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Cara Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 Jun 2019 (actual)
- Primary completion
- 29 Jun 2022 (actual)
- Study completion
- 29 Jun 2022 (actual)
- First posted
- 21 Jun 2019 (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.
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of twice-daily (BID) oral CR845 1.0 mg in patients with PBC with moderate-to-severe pruritus. The study includes a 16-week Treatment Period.
Detailed description
This study will consist of a Screening Visit, a 7-day Run-in Period, a 16-week Treatment Period, and a Follow-up Visit (approximately 7-10 days after the last dose of study drug). Informed consent will be obtained prior to performing any study-specific procedures.
The Screening Visit will occur within 7 to 28 days prior to randomization to assess eligibility.
Day 1 of the Treatment Period will be defined as the day of the administration of the first dose of study drug. 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 either placebo or CR845 tablets at a dose of 1.0 mg orally BID for 16 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CR845 1.0 mg | Active comparator | Drug: CR845 1.0 mgOral CR845 1.0 mg tablet administered twice daily |
| Placebo | Placebo comparator | Drug: PlaceboOral placebo tablet administered twice daily |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Confirmed diagnosis of PBC;
- If currently taking ursodeoxycholic acid (UDCA), should be on stable dose for >12 weeks prior to screening and plan on continuing to take UDCA throughout the study;
- If previously taking UDCA, should have discontinued its use >12 weeks prior to screening;
- Self-reports experiencing daily or near-daily pruritus during the month prior to screening;
- Prior to randomization has a mean baseline WI-NRS score indicative of moderate to severe pruritus.
Key exclusion criteria (8 listed)
- Presence of Child-Pugh Class C decompensated cirrhosis at screening;
- Itching secondary to biliary obstruction;
- History or presence of hepatocellular carcinoma, hepatic abscess, or acute portal vein thrombosis;
- Current placement on liver transplantation list with anticipated liver transplant during the course of the study or current Model for End-stage Liver Disease (MELD) score ≥15;
- Alanine aminotransferase or aspartate aminotransferase >5 × upper limit of normal at screening, or within 2 months prior to screening;
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 1.0 mgAlso: CR845, DifelikefalinOral CR845 1.0 mg administered twice daily | Drug | CR845 1.0 mg |
| PlaceboOral Placebo administered twice daily | Drug | Placebo |
Primary outcome
Change from baseline to Week 16 with respect to the weekly mean of the daily 24-hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score.
Time frame: Baseline, Week 16
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".
3 secondary outcomes
Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in total Skindex-10 Scale score
Time frame: Baseline, Week 16
Improvement in itch-related quality of life as assessed by the change from baseline to Week 16 in 5-D Itch Scale score
Time frame: Baseline, Week 16
Reduction of itch intensity as assessed by the proportion of patients achieving an improvement from baseline ≥3 points with respect to the weekly mean of the daily 24-hour WI-NRS score at Week 16
Time frame: Week 16
Results and safety
The study was stopped early (reason given: Slow enrollment due primarily to Covid-19). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2023.
- Individual participant dataSharing planned: No
Related trials for Cholestatic Pruritus
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J-LINX: Japan LINerixibat eXtension Study
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Evaluation of Maralixibat in Pruritus Associated With General Cholestatic Liver Disease (EXPAND)
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Not yet recruitingPhase 2
Nemolizumab for the Treatment of Moderate to Severe Chronic Hepatic Pruritus
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A Study to Evaluate Efficacy and Safety of an Investigational Drug Named Volixibat in Patients With Itching Caused by Primary Biliary Cholangitis
Primary Biliary Cholangitis, PBC
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
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CR845 1.0 mg in people with Cholestatic Pruritus, run by Cara Therapeutics, Inc. at 14 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 6 inclusion and 8 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 3 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 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 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.
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: Slow enrollment due primarily to Covid-19). 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?
Change from baseline to Week 16 with respect to the weekly mean of the daily 24-hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score. (time frame: Baseline, Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jul 2023.