A Phase 3, Phosphate Binder Switch Study of KHK7791 in Hyperphosphatemia Patients on Hemodialysis

JRCT ID: jRCT2071200108

Registered date:04/03/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Hyperphosphatemia Patients on Hemodialysis
• Date of first enrollment: 15/03/2021
• Target sample size: 200
• Study type: Interventional

Intervention(s)

Hemodialysis patients with hyperphosphatemia who have provided written consent will undergo a screening examination. During the dosing period, subjects administer KHK7791 twice daily just before meals for 52 weeks. Subjects will be underwent tests at scheduled visits at least weekly until Week 12, at least once every 2 weeks after completion of Week 12 test.
KHK7791 and phosphate binders are adjusted with the goal of controlling serum phosphorus concentration within a certain range based on the dose adjustment criteria described in the study protocol. It should be considered that phosphorus adsorbent should be switched to KHK7791 whenever feasible.

Outcome(s)

Primary Outcome

To investigate the safety of repeated administration of KHK7791 for 52 weeks while switching from a phosphate-binding agent to KHK7791 in Hemodialysis patients with hyperphosphatemia
- Adverse events
- Laboratory examination
- Vital signs
- Standard 12-lead ECG

Secondary Outcome

To investigate the efficacy of repeated administration of KHK7791 for 52 weeks while switching from a phosphate-binding agent to KHK7791 in hyperphosphatemic subjects undergoing hemodialysis.

Important secondary endpoint
- Achievement of at least 30% reduction of the total number of daily prescription tablets of phosphorus binders and KHK7791 from baseline in the last 3 weeks of the final assessment.
Other secondary endpoints
- The total number of phosphate binders and KHK7791 tablets prescribed daily, total weight of prescribed daily drugs, total volume of prescribed daily drugs and achievement of at least 30% reduction of prescribed daily drugs, at each time point after the start of treatment, and their change and percentage change from baseline.
- Changes in serum phosphorous levels from baseline values at each time point.
- Achievement/failure of the target serum phosphorus level (serum phosphorus level: =< 6.0) and Time when the target serum phosphorus level (serum phosphorus level: =< 6.0) was achieved.
- Achievement/failure of the target serum phosphorus level (serum phosphorus level: =< 5.5) and Time when the target serum phosphorus level (serum phosphorus level: =< 5.5) was achieved.
- Concentrations and Changes of Ca x P product and corrected serum calcium levels from baseline values at each time point.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Has voluntarily provided written informed consent to participate in the study.
2) Aged >= 20 years (expressed in completed years) at the time of providing informed consent.
3) Stable chronic renal failure patients who have undergone hemodialysis 3 times per week for at least 12 weeks until screening examination.
4) Dialysis conditions excluding dry weight, should have been unchanged during the last 2 weeks before screening examination.
5) The prescribed drug and dosage regimen should have been unchanged during the last 4 weeks before screening examination.
6) Serum phosphorus levels should be in the range of >= 3.5 and =< 7.0 mg/dL at screening examination.
7) If on any vitamin D, calcimimetics regimen, bisphosphonate, calcitonin preparations, selective estrogen receptor modulators or teriparatide preparations then the prescribed drug and dosage regimen should have been unchanged for the last 4 weeks before screening examination.
8) Kt/V urea >= 1.2 at the most recent test in routine medical practice before screening examination.

Exclude criteria

1) Peritoneal dialysis was performed within 12 weeks before screening examination.
2) iPTH > 600 pg/mL (should be based on the most recent value from patient's medical records before pre-enrollment)
3) History of inflammatory bowel disease (IBD) or diarrhea predominant irritable bowel syndrome
4) History of gastrectomy or enterectomy or having undergone gastrointestinal tract surgery within 3 months before screening examination.
5) Subjects who used anti RANKL preparations within 6 weeks before screening examination.
6) Subjects who used anti-sclerostin antibody preparations within 12 weeks before screening examination.
7) Severe heart disease, hepatic impairment, or concurrent cirrhosis.
8) Developed cerebrovascular disease or cardiovascular disease requiring hospitalization within 6 months before screening examination.
9) Uncontrollable hypertension or diabetes
10) Subjects experienced more than 3 times diarrhea or loose stool in a day at least six BSFS score more than two days in a week.
11) Scheduled for living donor kidney transplant, change in the mode of dialysis, home hemodialysis or plans to change the dialysis center during the study period.
12) Any diagnosis of or treatment of malignancy within 5 years before screening examination.
13) Tested positive for HIV or HTLV-1.
14) Expected to develop serious drug allergies such as anaphylactic shock, or any history of alcohol dependence, illicit drug use, severe mental illness, or drug abuse or addiction within 12 months before screening examination.
15) Not expected to live for more than 12 months.
16) Has received other study drugs within 4 weeks before screening examination. However, if there are concerns about the effects on the assessment of efficacy and safety of KHK7791, such as a 5-fold elimination half-life of another investigational product more than 4 weeks, these will be discussed with the sponsor.
17)Previous exposure to KHK7791.

Related Information

• Primary Sponsor: Kinoshita Jun
• Secondary ID(s): NCT04771780