A study to see how well PLS240 works in treating secondary hyperparathyroidism, and how safe it is, in end stage kidney disease participants who are on hemodialysis (PATH-2)

Phase 1

Conditions: ESKD participants with history of secondary hyperparathyroidism (SHPT) undergoing maintenance hemodialysis
MedDRA version: 20.0Level: PTClassification code: 10020708Term: Hyperparathyroidism secondary Class: 100000004860
Therapeutic area: Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
Therapeutic area: Diseases [C] - Hormonal diseases [C19]
Therapeutic area: Diseases [C] - Male Urogenital Diseases [C12]

Registration Number: CTIS2023-504339-41-00

Lead Sponsor: Pathalys Pharma Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 375

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 months and 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 assessments performed at 2 visits, at least 1 week apart, during the Active Screening period. iPTH may be tested up to 4 times during the Active Screening period. 4.Pre-dialysis central laboratory cCa must be =8.3 mg/dL on at least one assessment performed during the Active Screening period. cCa may be tested up to 3 times during the Active Screening period. 5.Dialysate calcium concentration =2.5 mEq/L (1.25 mmol/L) and stable for at least 4 weeks prior to signing the ICF. 6.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 signing the ICF, 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. 7.Participants receiving phosphate binders 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 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., maximum dose change =50%), in the opinion of the investigator or sub-investigator, within the 2 months prior to signing the ICF and remain stable through the screening period., 9.Female participants who are post-menopausal (‘post-menopausal’ women have had no menses for the previous year and are over the age of 50 years), or surgically sterilized, or have a medical condition that prevents pregnancy, or commit to remain abstinent during the study and for 2 weeks after the last dose of the investigational product (IP), or are willing to use highly effective contraception (see Section 8.8) during the study and for 2 weeks after the last dose of IP. Women of child-bearing potential must have a negative serum pregnancy test during the screening period. 10.Male participants who are willing to use highly effective contraception (see Section 8.8 ) when sexually active and will not donate sperm during the treatment phase and for 2 weeks after 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 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 course of treatment and final safety follow-up visit of the 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 12

Exclusion Criteria

1.Diagnosis of primary hyperparathyroidism 2.Pre-dialysis central laboratory Active Screening iPTH >1500 pg/mL on two or more occasions. iPTH may be tested up to 4 times during the Active Screening period 3.[Deleted] 4.History of parathyroid intervention including parathyroidectomy (PTx) and/or percutaneous ethanol injection therapy (PEIT) within 26 weeks before signing the ICF 5.Treatment with any prohibited medication as defined in protocol Section 8.3.1. 6.Anticipated or scheduled parathyroidectomy during the study period 7.Planned living-related or living-unrelated kidney transplant during the study period 8.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 signing the ICF 9.Noncompliant with hemodialysis (i.e., missing more than 3 dialysis sessions within 8 weeks prior to signing the ICF, unless absence is due to hospitalization) 10.Clinically significant abnormalities on screening laboratory tests (may repeat abnormal laboratory tests as defined in Section 7.4.1) according to the Investigator, including but not limited to the following: a.Serum albumin =3.0 g/dL b.Serum magnesium <1.5 mg/dL c.Serum P >8.0 mg/dL d.Hemoglobin <8.5 g/dL e.Platelet count <100,000 x106/L f.Serum transaminase (alanine transaminase [ALT] or Serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST] or serum glutamic oxaloacetic transaminase [SGOT]) = 2.5 times the upper limit of normal (ULN) during Active Screening, 11.Diagnosed with an unstable medical condition, defined as having been hospitalized, other than for dialysis vascular access intervention, within 30 days prior to signing the ICF, or otherwise unstable in the judgment of the investigator 12.History of malignancy within the last 2 years prior to signing the ICF (except squamous or basal cell skin cancers, or cervical carcinoma in situ) 13.Recent history (within 4 weeks prior to signing the ICF) of angina pectoris with symptoms that occur at rest or minimal activity. Chest pain on dialysis (within 8 weeks prior to signing the ICF) unless evaluated by a cardiologist with documentation that the chest pain is not due to cardiac ischemia 14.History of New York Heart Association (NYHA) Functional Class 3 or 4 heart failure (see Appendix 2) 15.History of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 4 months prior to signing the ICF 16.Stroke (cerebral infarction or cerebral hemorrhage) within 6 months prior to signing the ICF 17.Participant is receiving treatment for a seizure disorder or has a history of a seizure within 12 weeks prior to signing the ICF 18.Poorly controlled diabetes mellitus, in the judgment of the investigator or sub-investigator 19.Poorly controlled hypertension (defined as post-dialysis [seated if available] systolic pressure >180 mmHg and/or diastolic pressure >110 mmHg) at 2 or more dialysis sessions during the 2 weeks prior to signing the ICF 20.Enrolled in other invasive investigational device or investigational drug trials within at least 30 days prior to signing the ICF 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 >500msec on screening ECG 24