Uremic Pruritus
Conditions
Keywords
uremic pruritus, Hemodialysis
Brief summary
A Randomized, Double Blind, Placebo-Controlled study to assess the Safety, Local Tolerance, and Pharmacokinetics of LT5001 drug product in Hemodialysis Patients with Uremic Pruritus
Detailed description
In Part A, patient participation is expected to last up to 63 days, including a 28-day screening period(consisting of a 7-day diary run-in to build baseline itch NRS) and a 36-day on study period (consisting of 56 total doses from Day 1 to Day 29, and a 7 day follow-up/EOS visit at Day 36). In Part B, patient participation is expected to last up to 85 days, including a 28-day screening period (consisting of a 7-day diary run-in to build baseline itch NRS) and a 57-day on study treatment period.
Interventions
DRUGLT5001
LT5001 is administered twice daily.
DRUGPlacebo
LT5001 is administered twice daily.
Sponsors
Lumosa Therapeutics Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female 20 to 75 years of age, inclusive, at the time of signing informed consent. 2. Patient must have been receiving in-center hemodialysis for ≥ 3 months and currently on a schedule of 3 times per week. 3. Patient must have had at least 2 urea reduction ratio (URR) measurements ≥ 65%, at least 2 single-pool Kt/V measurements ≥ 1.2, or 1 single-pool Kt/V measurement ≥ 1.2 and 1 URR measurement ≥ 65% on different dialysis days within the last 3 month period prior to the Screening Visit. 4. Body weight ≥ 40 kg (not to exceed 115 kg) and BMI ≥ 18.0 and ≤ 31.0 kg/m2 at screening and Day 1 (after hemodialysis). 5. History of pruritus \> 4 weeks of duration 6. Females with childbearing potential (defined as women ≤50 years of age with a history of amenorrhea for \<12 months prior to study entry) must agree to use effective methods of contraception from screening through the last dose of study drug. 7. Males who are sexually active and whose partners are females of childbearing potential must agree to use condoms from screening through 90 days, whichever is longer, after administration of the last dose of study drug, and their partners must be willing to use a highly effective method of contraception from screening through 90 days after administration of the last dose of study drug. 8. Males must agree to not donate sperm from screening through 90 days, whichever is longer, after administration of the last dose of study drug. 9. Patient must have completed at least 6 days of Worst Itching Intensity NRS worksheets in the 7-day Diary run-in period and have a mean Worst Itching Intensity NRS score \> 4 prior to randomization. 10. Patients must be able to complete questionnaires, understand the study procedures, and communicate effectively with the study personnel.
Exclusion criteria
1. History of alcohol abuse, illicit drug use, physical dependence to any opioid or narcotic, or any history of drug abuse or addiction within 6 months of screening. 2. History of major surgery or trauma within 12 weeks of screening in the judgement of the investigator, or surgery planned during the study. 3. Has received ultraviolet B treatment, opioid antagonists (eg, naloxone, naltrexone), or opioid mixed agonist-antagonist (eg, nalbuphine) within 30 days prior to the Screening Visit or anticipated to receive such treatment during the study. 4. Has had a significant alteration in dialysis regimen within 2 weeks of the Screening Visit or anticipated to be receiving nocturnal dialysis, home hemodialysis treatment, or kidney transplant during the study. 5. Has any known history of allergic reaction to opioids. 6. History of latest positive serology test for HBV (HBsAg) or HCV (anti-HCV) within 1 year prior randomization consistent with current infection. Confirmatory tests will be allowed at the discretion of the investigator to rule out false positives. 7. Has any known history of HIV. 8. Positive pregnancy test or is lactating. 9. Has required peritoneal dialysis. 10. Alanine aminotransferase and/or aspartate aminotransferase concentration \> 2 x the ULN, or total bilirubin \> 1.8 x ULN, or hemoglobin concentration \< 9 g/dL at the Screening Visit. 11. Has taken other investigational drugs or participated in any clinical study within 30 days or 5 half-lives (if known) of the investigational drug's PK, PD, or biological activity (if known), whichever is longer, prior to first dose of study drug in this study or is currently participating in another clinical study. 12. Has received a vaccination within 3 days prior to administration of the first dose of study drug. 13. Has pruritus probably or definitely attributed to a cause other than renal disease or its complications such as atopic dermatitis, chronic urticarial, or hepatic pruritus caused by chronic liver disease. 14. Presence of skin infection (as defined by the investigator) on the area to be treated. 15. Any other condition or prior therapy that, in the investigator's opinion, would make the patient unsuitable for the study, or unable or unwilling to comply with the study procedures 16. Involved in the planning or conduct of this study. 17. Unwilling or unlikely to comply with the requirements of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Events With AE by Severity | Week 4 | The number of reported AE events by severity |
| Number of Patients With AE by Severity | Week 4 | Adverse events (AEs) were collected and categorized by severity (mild, moderate, or severe) according to standard clinical criteria. The outcome measure is defined as the number of patients who experienced at least one adverse event of each severity level during the study period. |
| The Number of Patients With AE by Causality | 4 weeks | Adverse events were assessed for their causal relationship to the study treatment by the investigator and categorized as related or not related. The outcome measure is defined as the number of patients who experienced at least one adverse event in each causality category during the study period. |
| Number of AE Event by Causality | week 4 | The number of reported events by causality |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Ctrough Exposure of LT5001 in Hemodialysis Patients. | Week 4 | The systemic trough (Ctrough) concentration of LT5001 was measured in hemodialysis patients at specified time points prior to the next scheduled dose using validated bioanalytical methods. The outcome measure is defined as the plasma concentration of LT5001 immediately before each dosing interval. |
| Change in Mean Worst Itching Intensity From Baseline to the End of Week 4 Using NRS. | Week 4 | The intensity of itch will be measured using the Numerical Rating Scale (NRS), a standardized scale for assessing the worst itching over the past 24 hours. The scale ranges from 0 to 10, where 0 represents no itching and 10 represents the worst itching imaginable. Higher scores indicate worse itch severity. The outcome measure is defined as the change in mean worst itching intensity from baseline to the end of Week 4. |
| Proportion of Patients With Changes in Numerical Rating Scale (>=2 Points, >=3 Points, >=4 Points) From Baseline | Week 4 | The Numerical Rating Scale (NRS) is an 11-point scale used to assess itch intensity, where scores range from 0 to 10, with 0 indicating no pain and 10 indicating the worst itch imaginable. A decrease in NRS score represents an improvement in itch severity. This outcome measures the proportion of patients who achieved a reduction of at least 2 points, 3 points, or 4 points from baseline in NRS score at Week 4. |
| Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in 5-D Pruritus Scale at the End of Week 4. | Week 4 | The 5-D Pruritus Scale (5-D Itch Scale) is a multidimensional questionnaire assessing itching across five key domains: Duration, Degree, Direction, Disability, and Distribution, to comprehensively evaluate the impact of itch on daily life. The scale ranges from 5 to 25, with 5 representing no itch and 25 representing severe itch. Each domain is scored from 1 (lowest) to 5 (highest). Higher scores indicate worse itch and poorer itch-related quality of life, whereas lower scores indicate better quality of life. The outcome measure is defined as the change from baseline in 5-D Pruritus Scale total score at the end of Week 4, with improvement reflected by a decrease in total score. |
| Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in Total Skindex-10 Scale Score at the End of Week 4. | Week 4 | The Skindex-10 Scale is a multidimensional questionnaire assessing itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. Each of the 10 items is scored from 0 to 6, resulting in a total score ranging from 0 to 60, where 0 represents never bothered/no impact and 60 represents always bothered/severe impact. Higher scores indicate worst itch-related quality of life, whereas lower scores indicate better quality of life. The outcome measure is defined as the change from baseline in total Skindex-10 Scale Score at the end of Week 4, with improvement reflected by a decrease in total score. |
Countries
Taiwan
Contacts
STUDY_DIRECTORJune Kuo
Lumosa Therapeutics
Participant flow
Recruitment details
The study was terminated after completion of Part A (18 participants). Part B was planned but not initiated.
Pre-assignment details
Participants underwent a 7-day run-in period prior to Part A. Only participants meeting eligibility criteria after the run-in period were enrolled into Part A. No participants entered Part B, as Part B was not initiated.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 8.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Taiwan | 18 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 4 Participants |
| weight | 67.0 kilogram STANDARD_DEVIATION 16.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 6 |
| other Total, other adverse events | 7 / 12 | 2 / 6 |
| serious Total, serious adverse events | 1 / 12 | 0 / 6 |
Outcome results
None listed