Uremic Pruritus
Conditions
Brief summary
Double-blind, Placebo-controlled study to confirm the superiority of MR13A9 to placebo, and followed by extension, open-label treatment to confirm long-term safety of MA13A9 in hemodialysis patients with pruritus.
Interventions
DRUGMR13A9
Intravenous administration
DRUGPlacebo
Intravenous administration
Sponsors
Kissei Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with Chronic Kidney Disease (CKD) has been on hemodialysis 3 times per week * Patient receiving treatment for itch * Patient has a baseline NRS score \> 4
Exclusion criteria
* Patient has pruritus cause other than CKD or its complications * Patients has hepatic cirrhosis * Patient has a known history of allergic reaction to opiates
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Mean NRS Score at Week 4 | 4 weeks | The change from baseline in the mean NRS score at each time point was calculated using an MMRM with the change from baseline in the mean NRS score at each time point as an objective variable, group, time point, and group-by-time point interaction as fixed effects, mean NRS score at baseline and presence or absence of prior treatment with nalfurafine hydrochloride as dynamic allocation factors as a covariate, and subjects as a random effect for data up to Week 4 of the double-blind period in FAS. Looking back on the period between the time of awakening on the previous day of assessment and the time of awakening on the day of assessment (including sleeping hours) once daily, subjects will assess the NRS score for the most severe itching by themselves. The most severe itching within the day will be assessed in integer on a scale ranging from 0 to 10, where 0 represents no itching and 10 represents worst itching imaginable. |
Countries
Japan
Participant flow
Recruitment details
Two hundred thirty subjects were screened. A total of 178 subjects included in the study and were randomly assigned to the study drug. The number of subjects in the double-blind period (6 weeks) was 178. The number of subjects who transitioned to the extension period (52 weeks) was 168. The number of subjects who completed Week 58 was 122.
Pre-assignment details
Previously treated hemodialysis patients with pruritus were enrolled in a 1:1 ratio to either MR13A9 0.5 μg/kg group or Placebo group. Subjects who received placebo in the double-blind period received MR13A9 0.5 μg/kg in the extension period.
Participants by arm
| Arm | Count |
|---|---|
| MR13A9 0.5 μg/kg Group The study drug was injected into the venous line of the dialysis circuit at the end of each dialysis session for 6 weeks (3 times weekly, 18 times in total).
The dose of the study drug (MR13A9) was determined according to mentioned below based on the subject's dry weight before dialysis on the start day of the screening period.
1. \<45.0 kg: 17.5 μg
2. \>=45.0 kg, \<65.0 kg: 25.0 μg
3. \>=65.0 kg, \<85.0 kg: 35.0 μg
4. \>=85.0 kg: 42.5 μg | 85 |
| Placebo Group The study drug was injected into the venous line of the dialysis circuit at the end of each dialysis session for 6 weeks (3 times weekly, 18 times in total). | 88 |
| Total | 173 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Period (6 Weeks) | 4 consecutive missed doses of the study drug | 0 | 1 | 0 | 0 |
| Double-blind Period (6 Weeks) | Adverse Event | 4 | 3 | 0 | 0 |
| Double-blind Period (6 Weeks) | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Double-blind Period (6 Weeks) | Protocol Violation | 0 | 1 | 0 | 0 |
| Extension Period (52 Weeks) | 7 consecutive missed doses of the study drug | 0 | 0 | 5 | 2 |
| Extension Period (52 Weeks) | Adverse Event | 0 | 0 | 6 | 18 |
| Extension Period (52 Weeks) | Difficulty in using iPad for efficacy evaluation | 0 | 0 | 0 | 1 |
| Extension Period (52 Weeks) | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Extension Period (52 Weeks) | Needed to prioritize the treatment of adverse events | 0 | 0 | 0 | 1 |
| Extension Period (52 Weeks) | The input rate of the symptom diary was low and no improvement | 0 | 0 | 0 | 1 |
| Extension Period (52 Weeks) | Transferred to another hospital | 0 | 0 | 2 | 0 |
| Extension Period (52 Weeks) | Withdrawal by Subject | 0 | 0 | 4 | 5 |
Baseline characteristics
| Characteristic | Placebo Group | MR13A9 0.5 μg/kg Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 52 Participants | 45 Participants | 97 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 40 Participants | 76 Participants |
| Age, Continuous | 64.1 years STANDARD_DEVIATION 12.7 | 64.4 years STANDARD_DEVIATION 10.5 | 64.2 years STANDARD_DEVIATION 11.7 |
| Age, Customized | 67 years | 66 years | 66 years |
| Average NRS Score | 6.40 points STANDARD_DEVIATION 1.28 | 6.57 points STANDARD_DEVIATION 1.29 | 6.48 points STANDARD_DEVIATION 1.28 |
| Disease Duration of Itch | 4.6 years STANDARD_DEVIATION 3.8 | 5.7 years STANDARD_DEVIATION 5.5 | 5.1 years STANDARD_DEVIATION 4.7 |
| Dry Weight at the start of Screening | 63.33 kg STANDARD_DEVIATION 12.94 | 62.64 kg STANDARD_DEVIATION 11.63 | 62.99 kg STANDARD_DEVIATION 12.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 88 Participants | 85 Participants | 173 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hemodialysis History | 7.9 years STANDARD_DEVIATION 6.7 | 8.4 years STANDARD_DEVIATION 7.6 | 8.1 years STANDARD_DEVIATION 7.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 88 Participants | 85 Participants | 173 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 88 participants | 85 participants | 173 participants |
| Sex: Female, Male Female | 16 Participants | 11 Participants | 27 Participants |
| Sex: Female, Male Male | 72 Participants | 74 Participants | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 89 | 1 / 89 | 2 / 85 | 2 / 83 |
| other Total, other adverse events | 27 / 89 | 24 / 89 | 74 / 85 | 74 / 83 |
| serious Total, serious adverse events | 7 / 89 | 10 / 89 | 33 / 85 | 38 / 83 |
Outcome results
Primary
Change From Baseline in the Mean NRS Score at Week 4
The change from baseline in the mean NRS score at each time point was calculated using an MMRM with the change from baseline in the mean NRS score at each time point as an objective variable, group, time point, and group-by-time point interaction as fixed effects, mean NRS score at baseline and presence or absence of prior treatment with nalfurafine hydrochloride as dynamic allocation factors as a covariate, and subjects as a random effect for data up to Week 4 of the double-blind period in FAS. Looking back on the period between the time of awakening on the previous day of assessment and the time of awakening on the day of assessment (including sleeping hours) once daily, subjects will assess the NRS score for the most severe itching by themselves. The most severe itching within the day will be assessed in integer on a scale ranging from 0 to 10, where 0 represents no itching and 10 represents worst itching imaginable.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MR13A9 0.5 μg/kg Group | Change From Baseline in the Mean NRS Score at Week 4 | -2.06 points | Standard Error 0.2 |
| Placebo Group | Change From Baseline in the Mean NRS Score at Week 4 | -1.09 points | Standard Error 0.2 |
p-value: <0.00195% CI: [-1.52, -0.42]MMRM