Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-2

Inclusion Criteria:

1. Aged 18 - 80 years at time of informed consent.

2. Prescribed hemodialysis for 3 times per week and on therapy for at least 3 monthsand has a delivered Kt/V≥1.2 within 4 weeks prior to signing the ICF.

3. Pre-dialysis central laboratory iPTH must be ≥400 pg/mL on at least two assessmentsperformed at 2 visits, at least 1 week apart during the Active Screening period.iPTH may be tested up to 4 times. at least performed at least a week after the previous iPTH.

4. Pre-dialysis central laboratory cCa must be ≥8.3 mg/dL on at least one assessmentperformed during the Active Screening period. cCa may be tested up to 3 times duringthe Active Screening period.

5. Dialysate calcium concentration ≥2.5 mEq/L (1.25 mmol/L) and stable for at least 4weeks prior to signing the ICF.

6. Participants receiving active Vitamin D sterols (e.g., doxercalciferol orcalcitriol) 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 monthsprior to signing the ICF, remain stable, as defined as no increase in dose, throughthe screening period, and be expected to maintain a stable dose, as defined as noincrease in dose, for the duration of the study.

7. Participants receiving phosphate binders must be on a stable dose (e.g., maximumdose change ≤50%), in the opinion of the investigator or sub-investigator, withinthe 2 months prior to signing the ICF, remain stable through the screening period,and be expected to maintain stable dose for the duration of the study.

8. Participants receiving calcium supplements must be on a stable dose (e.g., maximumdose change ≤50%), in the opinion of the investigator or sub-investigator, withinthe 2 months prior to signing the ICF and remain stable through the screeningperiod.

9. Female participants who are post-menopausal ('post-menopausal' women have had nomenses for the previous year and are over the age of 50 years), or surgicallysterilized, or have a medical condition that prevents pregnancy, or commit to remainabstinent during the study and for 2 weeks after the last dose of theinvestigational product (IP), or are willing to use highly effective contraceptionduring the study and for 2 weeks after the last dose of IP. Women of child-bearingpotential must have a negative serum pregnancy test during the screening period.

10. Male participants who are willing to use highly effective contraception whensexually active and will not donate sperm during the treatment phase and for 2 weeksafter the last dose of IP.

11. Voluntarily given written informed consent to participate in this study.

12. Agrees to not participate in another study of an investigational agent during thestudy 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 entryinto the Open-Label Extension Phase:

13. Have successfully completed the course of treatment and final safety follow-up visitof the Double-Blind Phase.

14. Voluntarily given written informed consent to participate in the Open-LabelExtension Phase of the study.

15. Prescribed hemodialysis for 3 times per week. 16. Continue to meet InclusionCriteria 9, 10, and 12.

Exclusion Criteria:

1. Diagnosis of primary hyperparathyroidism.

2. Pre-dialysis central laboratory Active Screening iPTH >1500 pg/mL on two or moreoccasions. iPTH may be tested up to 4 times during the Active Screening period.

3. History of parathyroid intervention including parathyroidectomy (PTx) andpercutaneous ethanol injection therapy (PEIT) within 26 weeks before signing theICF.

4. Treatment with any prohibited medication as defined in Section 8.3.1.

5. Anticipated or scheduled parathyroidectomy during the study period.

6. Planned living-related or living-unrelated kidney transplant during the studyperiod.

7. Change in mode of dialysis (e.g., from hemodialysis to hemodiafiltration, peritonealdialysis to hemodialysis, at home to in center dialysis), dialysate Caconcentration, or prescribed dialysis treatment time within 4 weeks before signingthe ICF.

8. Noncompliant with hemodialysis (i.e., missing more than 2 dialysis sessions within 8weeks prior to signing the ICF, unless absence is due to hospitalization ordialysis-access procedures).

9. Clinically significant abnormalities on screening laboratory tests (may repeatabnormal laboratory tests) according to the Investigator including but not limitedto the following:

10. Serum albumin ≤3.0 g/dL

11. Serum magnesium <1.5 mg/dL

12. Serum P >8.0 mg/dL

13. Hemoglobin <8.5 g/dL

14. Platelet count <100,000 x106/L

15. Serum transaminase (alanine transaminase [ALT] or serum glutamic pyruvictransaminase [SGPT], alanine transaminase [AST] or serum glutamic oxaloacetictransaminase [SGOT]) ≥2.5 times the upper limit of normal (ULN) during ActiveScreening.

16. Diagnosed with an unstable medical condition, defined as having been hospitalized,other than for dialysis vascular access intervention, within 30 days prior tosigning the TCF, or otherwise unstable in the judgment of the investigator.

17. History of malignancy within the last 2 years prior to signing the ICF (exceptsquamous or basal cell skin cancers, or cervical carcinoma in situ).

18. Recent history (within 4 weeks prior to signing the ICF) of angina pectoris withsymptoms that occur at rest or minimal activity. Chest pain on dialysis (within 8weeks prior to signing the ICF) unless evaluated by a cardiologist withdocumentation that the chest pain is not due to cardiac ischemia.

19. History of New York Heart Association (NYHA) Functional Class 3 or 4 heart failure.

20. History of myocardial infarction, coronary angioplasty, or coronary arterial bypassgrafting within the past 4 months prior to signing the ICF.

21. Stroke (cerebral infarction or cerebral hemorrhage) within 6 months prior to signingthe ICF.

22. Participant is receiving treatment for a seizure disorder or has a history of aseizure within 12 weeks prior to signing the ICF.

23. Poorly controlled diabetes mellitus, in the judgment of the investigator orsub-investigator.

24. Poorly controlled hypertension (defined as post-dialysis [seated if available]systolic pressure >180 mmHg or diastolic pressure >110 mmHg) at 2 or more dialysissessions during the 2 weeks prior to signing the ICF.

25. Enrolled in other invasive investigational device or investigational drug trials,within at least 30 days prior to signing the ICF or are receiving otherinvestigational agents (experimental dialysis machines are acceptable).

26. History of symptomatic ventricular dysrhythmias or Torsade de Pointes.

27. History of or family history of long QT syndrome.

28. QTcF >500 msec on screening ECG.

29. Pregnant or breast feeding.

30. Prior exposure or hypersensitivity to PLS240 or any of its components.

31. Current, recent, or suspected infection with SARS-CoV-2/COVID-19 within 4 weeksprior to signing the ICF.

32. In the opinion of the investigator, any disorder that would interfere withunderstanding and giving informed consent, or compliance with protocol requirements. Participants must be excluded from the Open-Label Extension Phase of the study, incase of the following at the time of entry into the Open-Label Extension Phase:

33. In the opinion of the investigator, continuation into the Open-Label Extension Phaseis not considered safe and/or feasible.

34. Continues to meet Exclusion Criterion #5.