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| ID | Type | Description | Link |
|---|---|---|---|
| CTR20220844 | Other Identifier | China CTR Number |
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| Name | Class |
|---|---|
| Tigermed Consulting Co., Ltd | INDUSTRY |
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This a multicentre study that consists of a 12-week double-blind period, and an optional 14-week open-label extension period and a 1-week follow-up period.
Total study duration for a single subject is 31 to 32 weeks with a 4-week screening period, a 12-week double-blind period, a 14-week optional open-label extension period, and a 1-week follow-up period. For subjects not participating in the open-label extension period, the total study duration is 17 weeks.
Difelikefalin will be administered in the double-blind and open-label period 3 times a week at the end of each dialysis session. The total dose of the investigational product will be determined based on the subject's prescription dry body weight.
The primary objective of the study is:
To evaluate the efficacy of difelikefalin 0.5 μg/kg compared to placebo in reducing the intensity of itch in HD Chinese subjects with moderate-to-severe pruritus.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 12-weeks double-blind period - Difelikefalin | Experimental |
| |
| 12-weeks double-blind period - Placebo | Placebo Comparator |
| |
| 14-weeks optional open-label period following the double-blind period - Difelikefalin | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Difelikefalin Injection | Drug | Participants receive Difelikefalin three times a week (0.5 micrograms/kg dry body weight). Difelikefalin is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Weekly Mean of the Daily 24-hour WI-NRS Score at Week 4 of the DB Period | On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a numerical rating scale (NRS) scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. The least square (LS) means of change from baseline to Week 4 in the weekly mean of the daily 24-hour WI-NRS score was estimated using the mixed model repeated measures (MMRM) method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline WI-NRS score as fixed continuous effects. | From Baseline to Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving Greater Than or Equal to (>=) 3-point Improvement From Baseline With Respect to the Weekly Mean of the Daily 24-hour WI-NRS in the DB Period | On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a NRS scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. Missing weekly mean WI-NRS data were imputed using missing at random (MAR) multiple imputation (MI) approach, assuming that participants who do not have weekly mean WI-NRS score at a timepoint would have similar weekly mean WI-NRS scores as other participants in their respective treatment arm who have complete data. The percentage of participants were estimated using a logistic regression model with terms for treatment group, baseline WI-NRS score, use of anti-itch medication during the week prior to randomisation, and the presence of specific medical conditions at baseline. |
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Inclusion Criteria:
Subjects with chronic kidney disease (CKD) on HD 3 times weekly for ≥12 weeks prior to the informed consent procedure (including the date of informed consent) who can continue HD without changing its frequency or method.
If female, is not pregnant, or nursing.
If female:
If male, agrees not to donate sperm after the first dose of investigational product administration until 7 days after the last dose of investigational product, and agrees to use a condom with spermicide or abstain from heterosexual intercourse during the study until 7 days after the last dose of investigational product.
Subjects with a prescription dry body weight between 40 and 100 kg, inclusive.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Milica Enoiu, PhD | Vifor Pharma Group | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator Site 25 | Baotou | China | ||||
| Investigator Site 01 |
CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
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Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.
Proposed research should seek to answer a previously unanswered important medical or scientific question.
Applicable country-specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.
If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.
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A total of 291 participants were screened, and 31 of these were screen failures. Of the screened participants, 260 were randomized in the study. Of these 260 participants, 227 completed the double blind (DB) treatment period and 217 of these participants entered the open-label extension (OLE) period of the study.
This study was conducted at 35 investigative sites in China.
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| ID | Title | Description |
|---|---|---|
| FG000 | Difelikefalin/Difelikefalin | Participants received Difelikefalin injected into the venous line of the dialysis circuit at the end of each dialysis session for up to 12 weeks (3 times weekly, 36 times in total) in the DB period. Upon completion of the DB period, participants who chose to enter the optional OLE period received Difelikefalin additionally for up to 14 weeks (3 times weekly), starting at Week 13, and until Week 26 inclusive. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| DB Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 30, 2022 | Apr 16, 2025 |
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| Placebo Injection | Drug | Participants receive Placebo three times a week (0.5 micrograms/kg dry body weight). Placebo is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis. |
|
| From Baseline, and at Weeks 4, 8, and 12 |
| Percentage of Participants Achieving at Least 4-point Improvement From Baseline With Respect to the Weekly Mean of the Daily 24-hour WI-NRS in the DB Period | On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a NRS scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. Missing weekly mean WI-NRS data were imputed using MAR-MI approach, assuming that participants who do not have weekly mean WI-NRS score at a timepoint would have similar weekly mean WI-NRS scores as other participants in their respective treatment arm who have complete data. | From Baseline, and at Weeks 4, 8, and 12 |
| Change From Baseline in the Weekly Mean of the 24-hour WI-NRS Score at Each Week of the DB Period | On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a NRS scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values was calculated for the analysis. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline WI-NRS score as fixed continuous effects. | From Baseline to Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 |
| Change From Baseline in Itch-related Quality-of-life (QoL) as Assessed by the 5-D Itch Scale Total Score (DB Period) | The 5-D itch scale is a questionnaire where participants assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution). The scores of each of the 5 domains are achieved separately and then summed together to obtain a total 5-D score. 5-D itch scale scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus) where a higher score indicates a more severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the 5-D itch scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment sequence, visit, and treatment sequence-by-visit-interaction as fixed categorical effects and baseline 5-D Itch score (total score) as fixed continuous effects. | From Baseline to Weeks 4, 8, and 12 |
| Change From Baseline in Itch-related QoL as Assessed by the 5-D Itch Scale Total Score (OLE Period) | The 5-D itch scale is a questionnaire where participants assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution). The scores of each of the 5 domains are achieved separately and then summed together to obtain a total 5-D score. 5-D itch scale scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus) where a higher score indicates a more severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the 5-D itch scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment sequence, visit, and treatment sequence-by-visit-interaction as fixed categorical effects and baseline 5-D Itch score (total score) as fixed continuous effects. | From Baseline to OLE Period - Weeks 4, 8, 12, and 14 |
| Change From Baseline in Itch-related QoL as Assessed by the Skindex-10 Scale Total Score (DB Period) | The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity. Participants are asked the question "During the past week, how often have you been bothered by" and respond by filling in 1 of 7 circles numbered from 0 (labelled with the anchor phrase "never bothered") to 6 (labelled as "always bothered") for each of the 10 questions. The total score is the sum of the numeric value of each answered question. Here, a higher score indicated a severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the Skindex-10 scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline skindex-10 scale score (total score) as fixed continuous effects. | From Baseline to Weeks 4, 8, and 12 |
| Change From Baseline in Itch-related QoL as Assessed by the Skindex-10 Scale Total Score (OLE Period) | The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity. Participants are asked the question "During the past week, how often have you been bothered by" and respond by filling in 1 of 7 circles numbered from 0 (labelled with the anchor phrase "never bothered") to 6 (labelled as "always bothered") for each of the 10 questions. The total score is the sum of the numeric value of each answered question. Here, a higher score indicated a severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the Skindex-10 scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline skindex-10 scale score (total score) as fixed continuous effects. | From Baseline to OLE Period - Weeks 4, 8, 12, and 14 |
| Patient Global Impression of Change | The Patient Global Impression of Change is a global participant reported outcome measure that assesses the change in itch (no change, improvement or worsening) overall relative to the start of the study. The scale has only 1 item, and the participant was asked to mark the category that best describes the change in itch ranging from "Very Much Improved" to "Very Much Worse". Number of participants within all individual categories are reported here. | At Week 12 |
| Number of Participants With Adverse Events (AEs) | Up to Week 27 (12 weeks in DB + 14 weeks in OLE +1 week of follow up) |
| Number of Participants With Clinically Significant Abnormal 12-lead Electrocardiogram (ECG) | Up to Week 27 (12 weeks in DB + 14 weeks in OLE +1 week of follow up) |
| Number of Participants With Clinically Relevant Change From Baseline in Vital Signs and Laboratory Evaluations | From baseline to Week 27 (12 weeks in DB + 14 weeks in OLE +1 week of follow up) |
| Beijing |
| China |
| Investigator Site 07 | Beijing | China |
| Investigator Site 26 | Changsha | China |
| Investigator Site 06 | Guangzhou | China |
| Investigator Site 12 | Jiaxing | China |
| Investigator Site 02 | Lanzhou | China |
| Investigator Site 34 | Mianyang | China |
| Investigator Site 03 | Nanjing | China |
| Investigator Site 10 | Nanjing | China |
| Investigator Site 19 | Nanjing | China |
| Investigator Site 36 | Nantong | China |
| Investigator Site 40 | Shanghai | China |
| Investigator Site 18 | Shenyang | China |
| Investigator Site 21 | Shenyang | China |
| Investigator Site 16 | Shenzhen | China |
| Investigator Site 08 | Shihezi | China |
| Investigator Site 32 | Shijiazhuang | China |
| Investigator Site 41 | Shijiazhuang | China |
| Investigator Site 20 | Taiyuan | China |
| Investigator Site 24 | Taiyuan | China |
| Investigator Site 39 | Tianjin | China |
| Investigator Site 04 | Ürümqi | China |
| Investigator Site 17 | Wuhan | China |
| Investigator Site 33 | Wuxi | China |
| Investigator Site 13 | Xiamen | China |
| Investigator Site 15 | Xianyang | China |
| Investigator Site 22 | Xining | China |
| Investigator Site 38 | Xinxiang | China |
| Investigator Site 11 | Yangzhou | China |
| Investigator Site 30 | Yibin | China |
| Investigator Site 29 | Yinchuan | China |
| Investigator Site 23 | Zhengzhou | China |
| Investigator Site 31 | Zhenjiang | China |
| Investigator Site 35 | Zhuzhou | China |
| FG001 | Placebo/Difelikefalin | Participants received Placebo injected into the venous line of the dialysis circuit at the end of each dialysis session matching to Difelikefalin for up to 12 weeks (3 times weekly, 36 times in total) in the DB period. Upon completion of the DB period, participants who chose to enter the optional OLE period received Difelikefalin additionally for up to 14 weeks (3 times weekly), starting at Week 13, and until Week 26 inclusive. |
| Treated |
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| COMPLETED |
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| NOT COMPLETED |
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| OLE Period |
|
|
Analysis was performed on the full analysis set (FAS). The FAS included all participants who were randomised to treatment, received at least 1 dose of investigational product and had a non-missing baseline assessment for the weekly mean of the daily 24-hour Worst Itch Numeric Rating Scale (WI-NRS) score.
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| ID | Title | Description |
|---|---|---|
| BG000 | DB Period: Difelikefalin | Participants received Difelikefalin injected into the venous line of the dialysis circuit at the end of each dialysis session for up to 12 weeks (3 times weekly, 36 times in total). |
| BG001 | DB Period: Placebo | Participants received Placebo injected into the venous line of the dialysis circuit at the end of each dialysis session matching to Difelikefalin for up to 12 weeks (3 times weekly, 36 times in total). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| WI-NRS | Mean | Standard Deviation | score on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Change From Baseline in the Weekly Mean of the Daily 24-hour WI-NRS Score at Week 4 of the DB Period | On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a numerical rating scale (NRS) scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. The least square (LS) means of change from baseline to Week 4 in the weekly mean of the daily 24-hour WI-NRS score was estimated using the mixed model repeated measures (MMRM) method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline WI-NRS score as fixed continuous effects. | Analysis was performed on the FAS. The FAS included all participants who were randomized to treatment, received at least 1 dose of investigational product and had a non-missing baseline assessment for the weekly mean of the daily 24-hour WI-NRS score. Here, 'overall number of participants analyzed', 'N' = participants with available data for this outcome measure. | Posted | Least Squares Mean | Standard Error | score on a scale | From Baseline to Week 4 |
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| Secondary | Percentage of Participants Achieving Greater Than or Equal to (>=) 3-point Improvement From Baseline With Respect to the Weekly Mean of the Daily 24-hour WI-NRS in the DB Period | On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a NRS scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. Missing weekly mean WI-NRS data were imputed using missing at random (MAR) multiple imputation (MI) approach, assuming that participants who do not have weekly mean WI-NRS score at a timepoint would have similar weekly mean WI-NRS scores as other participants in their respective treatment arm who have complete data. The percentage of participants were estimated using a logistic regression model with terms for treatment group, baseline WI-NRS score, use of anti-itch medication during the week prior to randomisation, and the presence of specific medical conditions at baseline. | Analysis was performed on FAS. The FAS included all participants who were randomized to treatment, received at least 1 dose of investigational product and had a non-missing baseline assessment for the weekly mean of the daily 24-hour WI-NRS score. Here, 'number analyzed', 'n' = participants with available data for each specified timepoint. | Posted | Number | 95% Confidence Interval | percentage of participants | From Baseline, and at Weeks 4, 8, and 12 |
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| Secondary | Percentage of Participants Achieving at Least 4-point Improvement From Baseline With Respect to the Weekly Mean of the Daily 24-hour WI-NRS in the DB Period | On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a NRS scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. Missing weekly mean WI-NRS data were imputed using MAR-MI approach, assuming that participants who do not have weekly mean WI-NRS score at a timepoint would have similar weekly mean WI-NRS scores as other participants in their respective treatment arm who have complete data. | Analysis was performed on FAS. The FAS included all participants who were randomized to treatment, received at least 1 dose of investigational product and had a non-missing baseline assessment for the weekly mean of the daily 24-hour WI-NRS score. Here, 'number analyzed', 'n' = participants with available data for each specified timepoint. | Posted | Number | 95% Confidence Interval | percentage of participants | From Baseline, and at Weeks 4, 8, and 12 |
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| Secondary | Change From Baseline in the Weekly Mean of the 24-hour WI-NRS Score at Each Week of the DB Period | On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a NRS scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values was calculated for the analysis. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline WI-NRS score as fixed continuous effects. | Analysis was performed on FAS. The FAS included all participants who were randomized to treatment, received at least 1 dose of investigational product and had a non-missing baseline assessment for the weekly mean of the daily 24-hour WI-NRS score. Here, 'number analyzed', 'n' = participants with available data for each specified timepoint. | Posted | Least Squares Mean | Standard Error | score on a scale | From Baseline to Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 |
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| Secondary | Change From Baseline in Itch-related Quality-of-life (QoL) as Assessed by the 5-D Itch Scale Total Score (DB Period) | The 5-D itch scale is a questionnaire where participants assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution). The scores of each of the 5 domains are achieved separately and then summed together to obtain a total 5-D score. 5-D itch scale scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus) where a higher score indicates a more severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the 5-D itch scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment sequence, visit, and treatment sequence-by-visit-interaction as fixed categorical effects and baseline 5-D Itch score (total score) as fixed continuous effects. | Analysis was performed on FAS. The FAS included all participants who were randomized to treatment, received at least 1 dose of investigational product and had a non-missing baseline assessment for the weekly mean of the daily 24-hour WI-NRS score. Here, 'number analyzed', 'n' = participants with available data for each specified timepoint. | Posted | Least Squares Mean | Standard Error | score on a scale | From Baseline to Weeks 4, 8, and 12 |
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| Secondary | Change From Baseline in Itch-related QoL as Assessed by the 5-D Itch Scale Total Score (OLE Period) | The 5-D itch scale is a questionnaire where participants assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution). The scores of each of the 5 domains are achieved separately and then summed together to obtain a total 5-D score. 5-D itch scale scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus) where a higher score indicates a more severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the 5-D itch scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment sequence, visit, and treatment sequence-by-visit-interaction as fixed categorical effects and baseline 5-D Itch score (total score) as fixed continuous effects. | Analysis was performed on the OLE Safety Analysis Set, which included all participants who received at least 1 dose of IP in the OLE period. Here, 'number analyzed', 'n' = participants with available data for each specified timepoint. | Posted | Least Squares Mean | Standard Error | score on a scale | From Baseline to OLE Period - Weeks 4, 8, 12, and 14 |
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| Secondary | Change From Baseline in Itch-related QoL as Assessed by the Skindex-10 Scale Total Score (DB Period) | The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity. Participants are asked the question "During the past week, how often have you been bothered by" and respond by filling in 1 of 7 circles numbered from 0 (labelled with the anchor phrase "never bothered") to 6 (labelled as "always bothered") for each of the 10 questions. The total score is the sum of the numeric value of each answered question. Here, a higher score indicated a severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the Skindex-10 scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline skindex-10 scale score (total score) as fixed continuous effects. | Analysis was performed on FAS. The FAS included all participants who were randomized to treatment, received at least 1 dose of investigational product and had a non-missing baseline assessment for the weekly mean of the daily 24-hour WI-NRS score. Here, 'number analyzed', 'n' = participants with available data for each specified timepoint. | Posted | Least Squares Mean | Standard Error | score on a scale | From Baseline to Weeks 4, 8, and 12 |
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| Secondary | Change From Baseline in Itch-related QoL as Assessed by the Skindex-10 Scale Total Score (OLE Period) | The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity. Participants are asked the question "During the past week, how often have you been bothered by" and respond by filling in 1 of 7 circles numbered from 0 (labelled with the anchor phrase "never bothered") to 6 (labelled as "always bothered") for each of the 10 questions. The total score is the sum of the numeric value of each answered question. Here, a higher score indicated a severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the Skindex-10 scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline skindex-10 scale score (total score) as fixed continuous effects. | For the OLE period analysis was performed on OLE-SAS, which included all participants who received at least 1 dose of IP in the OLE period. Here, 'number analyzed', 'n' = participants with available data for each specified timepoint. | Posted | Least Squares Mean | Standard Error | score on a scale | From Baseline to OLE Period - Weeks 4, 8, 12, and 14 |
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| Secondary | Patient Global Impression of Change | The Patient Global Impression of Change is a global participant reported outcome measure that assesses the change in itch (no change, improvement or worsening) overall relative to the start of the study. The scale has only 1 item, and the participant was asked to mark the category that best describes the change in itch ranging from "Very Much Improved" to "Very Much Worse". Number of participants within all individual categories are reported here. | Analysis was performed on FAS. The FAS included all participants who were randomized to treatment, received at least 1 dose of investigational product and had a non-missing baseline assessment for the weekly mean of the daily 24-hour WI-NRS score. Here, 'overall number of participants analyzed', 'N' = participants with available data for the outcome measure. | Posted | Count of Participants | Participants | At Week 12 |
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| Secondary | Number of Participants With Adverse Events (AEs) | Analysis was performed on safety analysis set in DB period (DB-SAF). DB-SAF included all randomized participants who received at least 1 dose of investigational product during the DB period. For the OLE period analysis was performed on OLE Safety Analysis Set, which included all participants who received at least 1 dose of IP in the OLE period. | Posted | Count of Participants | Participants | Up to Week 27 (12 weeks in DB + 14 weeks in OLE +1 week of follow up) |
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| Secondary | Number of Participants With Clinically Significant Abnormal 12-lead Electrocardiogram (ECG) | The DB and OLE SAS consisted of all participants who received at least 1 dose of investigational product during the DB period and OLE period, respectively. Participants were analysed according to the actual treatment received. Here, 'number analyzed', 'n' = participants with available data for each specified timepoint. | Posted | Count of Participants | Participants | Up to Week 27 (12 weeks in DB + 14 weeks in OLE +1 week of follow up) |
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| Secondary | Number of Participants With Clinically Relevant Change From Baseline in Vital Signs and Laboratory Evaluations | The DB and OLE SAS consisted of all participants who received at least 1 dose of investigational product during the DB period and OLE period, respectively. Participants were analysed according to the actual treatment received. | Posted | Count of Participants | Participants | From baseline to Week 27 (12 weeks in DB + 14 weeks in OLE +1 week of follow up) |
|
From Baseline up to Week 27 (12 weeks in DB + 14 weeks in OLE +1 week of follow-up)
The DB and OLE SAS consisted of all participants who received at least 1 dose of investigational product during the DB period and OLE period, respectively. Participants were analysed according to the actual treatment received.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DB Period: Difelikefalin | Participants received Difelikefalin injected into the venous line of the dialysis circuit at the end of each dialysis session for up to 12 weeks (3 times weekly, 36 times in total). | 0 | 129 | 18 | 129 | 85 | 129 |
| EG001 | DB Period: Placebo | Participants received Placebo injected into the venous line of the dialysis circuit at the end of each dialysis session matching to Difelikefalin for up to 12 weeks (3 times weekly, 36 times in total). | 0 | 130 | 12 | 130 | 66 | 130 |
| EG002 | OLE Period: Difelikefalin/Difelikefalin | Upon completion of the double-blind period, participants who received Difelikefalin in DB period, who chose to enter the optional OLE period, received Difelikefalin additionally for up to 14 weeks (3 times weekly), starting at Week 13, and until Week 26 inclusive. | 0 | 103 | 19 | 103 | 65 | 103 |
| EG003 | OLE Period: Placebo/Difelikefalin | Upon completion of the double-blind period, participants who received placebo in DB period, who chose to enter the optional OLE period, received Difelikefalin additionally for up to 14 weeks (3 times weekly), starting at Week 13, and until Week 26 inclusive. | 0 | 113 | 12 | 113 | 69 | 113 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Myocardial injury | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Cardiac failure chronic | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
| |
| Abdominal infection | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
| |
| Febrile infection | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
| |
| Arteriovenous fistula site complication | Injury, poisoning and procedural complications | MedDRA version 26.0 | Systematic Assessment |
| |
| Arteriovenous fistula occlusion | Injury, poisoning and procedural complications | MedDRA version 26.0 | Systematic Assessment |
| |
| Arteriovenous fistula thrombosis | Injury, poisoning and procedural complications | MedDRA version 26.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA version 26.0 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA version 26.0 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA version 26.0 | Systematic Assessment |
| |
| Corneal opacity | Eye disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Retinal artery occlusion | Eye disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Vitreous haemorrhage | Eye disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Cataract cortical | Eye disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Post herpetic neuralgia | Nervous system disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Venous stenosis | Vascular disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Renal cyst haemorrhage | Renal and urinary disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Invasive breast carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 26.0 | Systematic Assessment |
| |
| Vascular access placement | Surgical and medical procedures | MedDRA version 26.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Dialysis hypotension | Vascular disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA version 26.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 26.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version 26.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Study Disclosure Manager | CSL Behring | Use email contact | clinicaltrials@cslbehring.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: DB Period | Aug 12, 2024 | Apr 16, 2025 | SAP_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: OLE Period | Nov 28, 2024 | Apr 16, 2025 | SAP_002.pdf |
| ID | Term |
|---|---|
| C000657129 | difelikefalin |
Not provided
Not provided
Not provided
| Withdrawal by Subject |
|
| Other: Unspecified |
|
| Male |
|
Testing of primary efficacy endpoint was 2-sided and conducted at the 5% significance level. The efficacy of difelikefalin was to be declared for this study if null hypothesis of no treatment difference in the primary efficacy analysis was rejected in favor of the alternative that participants randomized to difelikefalin experience significantly different itching compared to participants randomized to placebo. The null hypothesis was to be rejected if the 2-sided p value was less than (<) 0.05.
| OG001 | DB Period: Placebo | Participants received Placebo injected into the venous line of the dialysis circuit at the end of each dialysis session matching to Difelikefalin for up to 12 weeks (3 times weekly, 36 times in total). |
|
|
Participants received Placebo injected into the venous line of the dialysis circuit at the end of each dialysis session matching to Difelikefalin for up to 12 weeks (3 times weekly, 36 times in total).
|
|
Participants received Placebo injected into the venous line of the dialysis circuit at the end of each dialysis session matching to Difelikefalin for up to 12 weeks (3 times weekly, 36 times in total). |
|
|
| OG001 | DB Period: Placebo | Participants received Placebo injected into the venous line of the dialysis circuit at the end of each dialysis session matching to Difelikefalin for up to 12 weeks (3 times weekly, 36 times in total). |
|
|
| OG001 |
| OLE Period: Placebo/Difelikefalin |
Upon completion of the DB period, participants who received placebo in DB period, who chose to enter the optional OLE period, received Difelikefalin additionally for up to 14 weeks (3 times weekly), starting at Week 13, and until Week 26 inclusive. |
|
|
| OG001 | DB Period: Placebo | Participants received Placebo injected into the venous line of the dialysis circuit at the end of each dialysis session matching to Difelikefalin for up to 12 weeks (3 times weekly, 36 times in total). |
|
|
| OG001 | OLE Period: Placebo/Difelikefalin | Upon completion of the DB period, participants who received placebo in DB period, who chose to enter the optional OLE period, received Difelikefalin additionally for up to 14 weeks (3 times weekly), starting at Week 13, and until Week 26 inclusive. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG003 | OLE Period: Placebo/Difelikefalin | Upon completion of the DB period, participants who received placebo in DB period, who chose to enter the optional OLE period, received Difelikefalin additionally for up to 14 weeks (3 times weekly), starting at Week 13, and until Week 26 inclusive. |
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|