Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-2

Secondary Hyperparathyroidism Clinical Trial

— PATH-2  

Official title:

A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Dose-Titrated PLS240 in the Treatment of Secondary Hyperparathyroidism in Individuals With End Stage Kidney Disease on Hemodialysis (PATH-2) With an Open-Label Extension

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05836220
• Other study ID #: PP3003
• Secondary ID: 2023-504339-41
• Status: Recruiting
• Phase: Phase 3
• Start date: May 15, 2023
• Est. completion date: May 2025

Study information

• Verified date: May 2024
• Source: Pathalys Pharma
• Contact: Pathalys Clinical Trials
• Phone: Please reach out by email
• Email: clinicaltrials[@]pathalys.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to evaluate the efficacy and safety of PLS240 in patients with hemodialysis-dependent end stage kidney disease (ESKD) and secondary hyperparathyroidism (SHPT). The study consists of two phases. First, a placebo-controlled, double-blind phase where patients will be randomly assigned to either receive dose-titrated PLS240 or matching placebo for 27 weeks. After the completion of the double-blind phase, patients will be eligible to enroll in the open-label extension phase, where they will receive dose-titrated PLS240 for an additional 26 weeks. Throughout the duration of the study, patients will be expected to attend multiple study visits where an investigator will collect blood, preform electrocardiograms (ECGs) and physical exams, and further assess the safety and efficacy of PLS240.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 375
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

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 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 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 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. History of parathyroid intervention including parathyroidectomy (PTx) and percutaneous ethanol injection therapy (PEIT) within 26 weeks before signing the ICF.

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 study period.

7. 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.

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

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

1. Serum albumin =3.0 g/dL

2. Serum magnesium <1.5 mg/dL

3. Serum P >8.0 mg/dL

4. Hemoglobin <8.5 g/dL

5. Platelet count <100,000 x106/L

6. 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) during Active Screening.

10. 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 TCF, or otherwise unstable in the judgment of the investigator.

11. 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).

12. 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.

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

14. History of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 4 months prior to signing the ICF.

15. Stroke (cerebral infarction or cerebral hemorrhage) within 6 months prior to signing the ICF.

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

17. Poorly controlled diabetes mellitus, in the judgment of the investigator or sub-investigator.

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

19. 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).

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

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

22. QTcF >500 msec on screening ECG.

23. Pregnant or breast feeding.

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

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

26. 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:

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

28. Continues to meet Exclusion Criterion #5. 29. iPTH >1500 pg/mL at the final assessment during the EAP and at the Follow-up visit of the Double-Blind Phase.

Related Conditions & MeSH terms

• End Stage Kidney Disease
• Hyperparathyroidism
• Hyperparathyroidism, Secondary
• Kidney Diseases
• Kidney Failure, Chronic
• Neoplasm Metastasis
• Secondary Hyperparathyroidism

Intervention

Drug:
• PLS240
Participants will receive intravenous (IV) PLS240 three times per week for 27 weeks.
• Placebo
Participants will receive intravenous (IV) placebo, containing no active drug, three times per week for 27 weeks.
• Open-Label Extension PLS240
Participants will receive intravenous (IV) PLS240 three times per week for a maximum of 26 weeks.

Locations

Country	Name	City	State
Bulgaria	Site Number: BGR001-2	Gabrovo
Bulgaria	Site Number: BGR003-2	Lom	Montana
Bulgaria	Site Number: BGR002-2	Ruse
Bulgaria	Site Number: BGR004-2	Varna
Poland	Site Number: POL001-2	Lódz	Lódzkie
Poland	Site Number: POL004-2	Olkusz	Malopolskie
Poland	Site Number: POL002-2	Poznan	Wielkopolskie
Poland	Site Number: POL003-2	Pszczyna	Slaskie
Poland	Site Number: POL005-2	Warszawa	Mazowieckie
Portugal	Site Number: PRT001-2	Carnaxide
Portugal	Site Number: PRT002-2	Covilhã	Castelo Branco
Portugal	Site Number: PRT003-2	Lisboa
Serbia	Site Number: SRB003-2	Belgrade
Serbia	Site Number: SRB005-2	Beograd	Belgrade
Serbia	Site Number: SRB001-2	Kruševac
Serbia	Site Number: SRB002-2	Niš
Serbia	Site Number: SRB004-2	Užice
Spain	Site Number: ESP003-2	Córdoba	Cordoba
Spain	Site Number: ESP005-2	Manises	Valencia
United States	Site Number: USA007-2	Amherst	New York
United States	Site Number: USA039-2	Anaheim	California
United States	Site Number: USA023-2	Arvada	Colorado
United States	Site Number: USA031-2	Aurora	Colorado
United States	Site Number: USA041-2	Boca Raton	Florida
United States	Site Number: USA053-2	Charlotte	North Carolina
United States	Site Number: USA001-2	Chula Vista	California
United States	Site Number: USA013-2	Columbus	Georgia
United States	Site Number: USA026-2	Durham	North Carolina
United States	Site Number: USA003-2	El Centro	California
United States	Site Number: USA011-2	El Paso	Texas
United States	Site Number: USA020-2	Escondido	California
United States	Site Number: USA051-2	Fairfax	Virginia
United States	Site Number: USA004-2	Fort Myers	Florida
United States	Site Number: USA042-2	Fresno	California
United States	Site Number: USA034-2	Fullerton	California
United States	Site Number: USA046-2	Glendale	California
United States	Site Number: USA019-2	Granada Hills	California
United States	Site Number: USA055-2	Greenville	Texas
United States	Site Number: USA002-2	Hollywood	Florida
United States	Site Number: USA025-2	Kalamazoo	Michigan
United States	Site Number: USA027-2	Knoxville	Tennessee
United States	Site Number: USA005-2	La Mesa	California
United States	Site Number: USA044-2	Lancaster	California
United States	Site Number: USA029-2	Live Oak	Texas
United States	Site Number: USA030-2	Los Angeles	California
United States	Site Number: USA043-2	Los Angeles	California
United States	Site Number: USA017-2	Middlebury	Connecticut
United States	Site Number: USA016-2	Minneapolis	Minnesota
United States	Site Number: USA028-2	Mishawaka	Indiana
United States	Site Number: USA022-2	Moorpark	California
United States	Site Number: USA054-2	New Orleans	Louisiana
United States	Site Number: USA015-2	Newark	Delaware
United States	Site Number: USA033-2	Northridge	California
United States	Site Number: USA049-2	Northridge	California
United States	Site Number: USA045-2	Roseburg	Oregon
United States	Site Number: USA048-2	Roseville	Michigan
United States	Site Number: USA038-2	Saint George	Utah
United States	Site Number: USA008-2	San Antonio	Texas
United States	Site Number: USA012-2	San Antonio	Texas
United States	Site Number: USA018-2	San Dimas	California
United States	Site Number: USA035-2	South Miami	Florida
United States	Site Number: USA010-2	Spartanburg	South Carolina
United States	Site Number: USA021-2	Tarzana	California
United States	Site Number: USA056-2	Tarzana	California
United States	Site Number: USA009-2	Toledo	Ohio
United States	Site Number: USA052-2	Victorville	California
United States	Site Number: USA037-2	Virginia Beach	Virginia
United States	Site Number: USA006-2	Waxahachie	Texas
United States	Site Number: USA024-2	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Pathalys Pharma	Launch Therapeutics

Countries where clinical trial is conducted

United States,  Bulgaria,  Poland,  Portugal,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of PLS240 treated participants compared to the portion of placebo treated participants with a =30% decrease in mean iPTH	Double-Blind Phase only. This measurement will be calculated based on the Efficacy Assessment Period (Weeks 22 - 27) relative to the mean baseline iPTH (all Active Screening and predose Day 1 iPTH values).	each visit from screening through week 27
Primary	Open-Label Phase: Proportion of participants with a corrected serum calcium (cCa) <7.5 mg/dL		up to week 28
Primary	Open-Label Phase: Proportion of participants with a corrected serum calcium (cCa) <8.3 mg/dL		up to week 28
Primary	Open-Label Phase: Number of AE's		up to week 28
Primary	Open-Label Phase: Number of SAE's		up to week 28