Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-1 (PATH-1)

Inclusion Criteria: Aged 18 - 80 years at time of informed consent. Prescribed hemodialysis for 3 times per week and on therapy for at least 3 months and has a delivered Kt/V≥1.2 within 4 weeks prior to screening laboratory assessment. Pre-dialysis central laboratory screening iPTH must be ≥450 pg/mL on two measurements performed at 2 visits at least 1 week apart. Only one (1) repeat iPTH is allowed and must be at least performed at least a week after the previous iPTH. cCa before dialysis ≥8.4 mg/dL at the time of screening (may be repeated once). Dialysate calcium concentration ≥2.5 mEq/L (1.25 mmol/L) and stable for at least 4 weeks prior to screening laboratory assessments. Participants receiving active Vitamin D sterols (e.g., doxercalciferol or calcitriol) to manage SHPT must be on a stable dose (e.g., maximum dose change ≤50%), in the opinion of the investigator or sub-investigator, within the 2 months prior to screening laboratory assessments, remain stable, as defined as no increase in dose, through the screening period, and be expected to maintain a stable dose, as defined as no increase in dose, for the duration of the study. Participants receiving phosphate binders must be on a stable dose (e.g., maximum dose change ≤25%), in the opinion of the investigator or sub-investigator, within the 2 months prior to screening laboratory assessments, remain stable through the screening period, and be expected to maintain stable dose for the duration of the study. Participants receiving calcium supplements must be on a stable dose (e.g., maximum dose change ≤25%), in the opinion of the investigator or sub-investigator, within the 2 months prior to screening laboratory assessments and remain stable through the screening period. Female participants who are post-menopausal (post-menopausal defined as no menses for the previous 1 year and over the age of 50 years), surgically sterilized, have a medical condition that prevents pregnancy, commit to remain abstinent during the study and 2 weeks after the last dose of the investigational product, or are willing to use highly effective contraception during the study and for 2 weeks after the last dose of investigational product (IP). Women of child-bearing potential must have a negative serum pregnancy test during the screening period. Male participants who are willing to use highly effective contraception when sexually active and will not donate sperm during the treatment phase and for 2 weeks after the last dose of investigational product. Voluntarily given written informed consent to participate in this study. Agrees to not participate in another study of an investigational agent during the study. To be eligible for inclusion into the Open-Label Extension Phase of the study, participants must fulfill the additional following criteria at the time of entry into the Open-Label Extension Phase: 13. Have successfully completed the final safety follow-up visit of Double-Blind Phase. 14. Voluntarily given written informed consent to participate in the Open-Label Extension Phase of the study. 15. Prescribed hemodialysis for 3 times per week. 16. Continue to meet Inclusion Criteria 9, 10, and 12e. Exclusion Criteria: Diagnosis of primary hyperparathyroidism. Screening iPTH >1500 pg/mL. Screening iPTH <450 pg/mL (see entry criteria regarding repeat values). History of parathyroid intervention including parathyroidectomy (PTx) and percutaneous ethanol injection therapy (PEIT) within 26 weeks before screening. Treatment with any prohibited medication as defined in Section 8.3.1. Anticipated or scheduled parathyroidectomy during the study period. Planned living-related or living-unrelated kidney transplant during the study period. Change in mode of dialysis (e.g., from hemodialysis to hemodiafiltration, peritoneal dialysis to hemodialysis, at home to in center dialysis), dialysate Ca concentration, or prescribed dialysis treatment time within 4 weeks before screening. Noncompliant with hemodialysis (i.e., missing more than 2 dialysis sessions within 8 weeks prior to screening, unless absence is due to hospitalization or dialysis-access procedures). Clinically significant abnormalities on screening laboratory tests during the ≈4 weeks prior to starting IP according to the Investigator including but not limited to the following: Serum albumin ≤3.0 g/dL Serum magnesium <1.5 mg/dL Serum P >8.0 mg/dL Hemoglobin <8.5 g/dL Platelet count <100,000 x106/L Serum transaminase (alanine transaminase [ALT] or serum glutamic pyruvic transaminase [SGPT], alanine transaminase [AST] or serum glutamic oxaloacetic transaminase [SGOT]) ≥2.5 times the upper limit of normal (ULN) at screening. 11. Diagnosed with an unstable medical condition, defined as having been hospitalized, other than for dialysis vascular access intervention, within 30 days before screening, or otherwise unstable in the judgment of the investigator. 12. History of malignancy within the last 2 years prior to screening (except squamous or basal cell skin cancers, or cervical carcinoma in situ). 13. Recent history (within 4 weeks of screening) of angina pectoris with symptoms that occur at rest or minimal activity. 14. History of New York Heart Association (NYHA) Functional Class 3 or 4 heart failure. 15. History of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 4 months prior to screening. 16. Stroke (cerebral infarction or cerebral hemorrhage) within 6 months before screening. 17. Participant is receiving treatment for a seizure disorder or has a history of a seizure within 12 weeks prior to screening. 18. Poorly controlled diabetes mellitus, in the judgment of the investigator or sub-investigator. 19. Poorly controlled hypertension (systolic pressure >180 mmHg or diastolic pressure >110 mmHg in 2 or more pre-dialysis measurements during the 2 weeks before screening). 20. Currently enrolled in, or have not yet completed at least 30 days before Baseline/Day 1 other invasive investigational device or investigational drug trials, or are receiving other investigational agents (experimental dialysis machines are acceptable). 21. History of symptomatic ventricular dysrhythmias or Torsade de Pointes. 22. History of or family history of long QT syndrome. 23. QTcF >500 msec on screening ECG. 24. Pregnant or breast feeding. 25. Prior exposure or hypersensitivity to PLS240 or any of its components. 26. Current, recent, or suspected infection within 4 weeks of screening of SARS-CoV-2/COVID-19. 27. In the opinion of the investigator, any disorder that would interfere with understanding and giving informed consent, or compliance with protocol requirements. Participants must be excluded from the Open-Label Extension Phase of the study, in case of the following at the time of entry into the Open-Label Extension Phase: 28. In the opinion of the investigator, continuation into the Open-Label Extension Phase is not considered safe and/or feasible. 29. Continues to meet Exclusion Criterion #5 30. iPTH >1500 pg/mL at the Follow-up visit of the Double-Blind Phase.