Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-2

Trial Title: Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-2

NCT ID: NCT05836220

Condition: Secondary Hyperparathyroidism
End Stage Kidney Disease

Conditions: Official terms:
Neoplasm Metastasis
Kidney Diseases
Kidney Failure, Chronic
Hyperparathyroidism
Hyperparathyroidism, Secondary

Study type: Interventional

Study phase: Phase 3

Overall status: Active, not recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Intervention:

Intervention type: Drug
Intervention name: PLS240
Description: Participants will receive intravenous (IV) PLS240 three times per week for 27 weeks.
Arm group label: Double-Blind Phase PLS240

Intervention type: Drug
Intervention name: Placebo
Description: Participants will receive intravenous (IV) placebo, containing no active drug, three times per week for 27 weeks.
Arm group label: Double-Blind Phase Placebo

Intervention type: Drug
Intervention name: Open-Label Extension PLS240
Description: Participants will receive intravenous (IV) PLS240 three times per week for a maximum of 26 weeks.
Arm group label: Open-Label Extension Phase PLS240

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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: No

Locations:

Facility:
Name: Site Number: USA039-2

Address:
City: Anaheim
Zip: 92801-6731
Country: United States

Facility:
Name: Site Number: USA001-2

Address:
City: Chula Vista
Zip: 91910-3813
Country: United States

Facility:
Name: Site Number: USA020-2

Address:
City: Escondido
Zip: 92025-4402
Country: United States

Facility:
Name: Site Number: USA042-2

Address:
City: Fresno
Zip: 93720-3389
Country: United States

Facility:
Name: Site Number: USA034-2

Address:
City: Fullerton
Zip: 92832-3037
Country: United States

Facility:
Name: Site Number: USA046-2

Address:
City: Glendale
Zip: 91205-3313
Country: United States

Facility:
Name: Site Number: USA019-2

Address:
City: Granada Hills
Zip: 91344-7407
Country: United States

Facility:
Name: Site Number: USA005-2

Address:
City: La Mesa
Zip: 91942-3017
Country: United States

Facility:
Name: Site Number: USA044-2

Address:
City: Lancaster
Zip: 93534-2831
Country: United States

Facility:
Name: Site Number: USA030-2

Address:
City: Los Angeles
Zip: 90022-4302
Country: United States

Facility:
Name: Site Number: USA043-2

Address:
City: Los Angeles
Zip: 90033
Country: United States

Facility:
Name: Site Number: USA022-2

Address:
City: Moorpark
Zip: 93021-3352
Country: United States

Facility:
Name: Site Number: USA049-2

Address:
City: Northridge
Zip: 91324-2927
Country: United States

Facility:
Name: Site Number: USA033-2

Address:
City: Northridge
Zip: 91324-3528
Country: United States

Facility:
Name: Site Number: USA003-2

Address:
City: San Diego
Zip: 92111-3636
Country: United States

Facility:
Name: Site Number: USA018-2

Address:
City: San Dimas
Zip: 91773-3539
Country: United States

Facility:
Name: Site Number: USA056-2

Address:
City: Tarzana
Zip: 91356-2806
Country: United States

Facility:
Name: Site Number: USA021-2

Address:
City: Tarzana
Zip: 91356-3647
Country: United States

Facility:
Name: Site Number: USA052-2

Address:
City: Victorville
Zip: 92395-8322
Country: United States

Facility:
Name: Site Number: USA023-2

Address:
City: Arvada
Zip: 80002-3714
Country: United States

Facility:
Name: Site Number: USA031-2

Address:
City: Aurora
Zip: 80045-7202
Country: United States

Facility:
Name: Site Number: USA017-2

Address:
City: Middlebury
Zip: 06762-2843
Country: United States

Facility:
Name: Site Number: USA015-2

Address:
City: Newark
Zip: 19713-2081
Country: United States

Facility:
Name: Site Number: USA004-2

Address:
City: Fort Myers
Zip: 33908-4154
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Facility:
Name: Site Number: USA002-2

Address:
City: Hollywood
Zip: 33024-2776
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Facility:
Name: Site Number: USA041-2

Address:
City: Orlando
Zip: 32801
Country: United States

Facility:
Name: Site Number: USA035-2

Address:
City: South Miami
Zip: 33143-5522
Country: United States

Facility:
Name: Site Number: USA013-2

Address:
City: Columbus
Zip: 31904-3603
Country: United States

Facility:
Name: Site Number: USA028-2

Address:
City: Mishawaka
Zip: 46545-3519
Country: United States

Facility:
Name: Site Number: USA024-2

Address:
City: Wichita
Zip: 67214-2944
Country: United States

Facility:
Name: Site Number: USA054-2

Address:
City: New Orleans
Zip: 70112
Country: United States

Facility:
Name: Site Number: USA048-2

Address:
City: Detroit
Zip: 48236-2169
Country: United States

Facility:
Name: Site Number: USA025-2

Address:
City: Kalamazoo
Zip: 49007-3889
Country: United States

Facility:
Name: Site Number: USA016-2

Address:
City: Minneapolis
Zip: 55404-1212
Country: United States

Facility:
Name: Site Number: USA007-2

Address:
City: Amherst
Zip: 14228-2792
Country: United States

Facility:
Name: Site Number: USA053-2

Address:
City: Charlotte
Zip: 28208-3876
Country: United States

Facility:
Name: Site Number: USA026-2

Address:
City: Durham
Zip: 27704-2147
Country: United States

Facility:
Name: Site Number: USA009-2

Address:
City: Toledo
Zip: 43606-1171
Country: United States

Facility:
Name: Site Number: USA045-2

Address:
City: Roseburg
Zip: 97471-6214
Country: United States

Facility:
Name: Site Number: USA010-2

Address:
City: Greenville
Zip: 29605-4019
Country: United States

Facility:
Name: Site Number: USA027-2

Address:
City: Knoxville
Zip: 37923-3624
Country: United States

Facility:
Name: Site Number: USA011-2

Address:
City: El Paso
Zip: 79925-4828
Country: United States

Facility:
Name: Site Number: USA029-2

Address:
City: Live Oak
Zip: 78233-4767
Country: United States

Facility:
Name: Site Number: USA055-2

Address:
City: Prosper
Zip: 75078-1411
Country: United States

Facility:
Name: Site Number: USA012-2

Address:
City: San Antonio
Zip: 78221-3019
Country: United States

Facility:
Name: Site Number: USA008-2

Address:
City: San Antonio
Zip: 78251-4125
Country: United States

Facility:
Name: Site Number: USA006-2

Address:
City: Waxahachie
Zip: 75165-1399
Country: United States

Facility:
Name: Site Number: USA038-2

Address:
City: Saint George
Zip: 84790-5898
Country: United States

Facility:
Name: Site Number: USA051-2

Address:
City: Fairfax
Zip: 22033-1907
Country: United States

Facility:
Name: Site Number: USA037-2

Address:
City: Norfolk
Zip: 23507-1901
Country: United States

Facility:
Name: Site Number: BGR003-2

Address:
City: Lom
Zip: 3600
Country: Bulgaria

Facility:
Name: Site Number: BGR001-2

Address:
City: Gabrovo
Zip: 5300
Country: Bulgaria

Facility:
Name: Site Number: BGR002-2

Address:
City: Ruse
Zip: 7002
Country: Bulgaria

Facility:
Name: Site Number: BGR004-2

Address:
City: Varna
Zip: 9000
Country: Bulgaria

Facility:
Name: Site Number: POL004-2

Address:
City: Tomaszów Mazowiecki
Zip: 97-200
Country: Poland

Facility:
Name: Site Number: POL001-2

Address:
City: Łódź
Zip: 90-242
Country: Poland

Facility:
Name: Site Number: POL005-2

Address:
City: Warszawa
Zip: 02-758
Country: Poland

Facility:
Name: Site Number: POL002-2

Address:
City: Poznań
Zip: 60-214
Country: Poland

Facility:
Name: Site Number: PRT002-2

Address:
City: Covilhã
Zip: 6200-000
Country: Portugal

Facility:
Name: Site Number: PRT001-2

Address:
City: Carnaxide
Zip: 2790-134
Country: Portugal

Facility:
Name: Site Number: PRT003-2

Address:
City: Lisboa
Zip: 1250-203
Country: Portugal

Facility:
Name: Site Number: SRB005-2

Address:
City: Beograd
Zip: 11080
Country: Serbia

Facility:
Name: Site Number: SRB003-2

Address:
City: Belgrade
Zip: 11000
Country: Serbia

Facility:
Name: Site Number: SRB001-2

Address:
City: Kruševac
Zip: 37000
Country: Serbia

Facility:
Name: Site Number: SRB002-2

Address:
City: Niš
Zip: 18000
Country: Serbia

Facility:
Name: Site Number: SRB004-2

Address:
City: Užice
Zip: 31000
Country: Serbia

Facility:
Name: Site Number: ESP003-2

Address:
City: Córdoba
Zip: 14004
Country: Spain

Facility:
Name: Site Number: ESP005-2

Address:
City: Manises
Zip: 46940
Country: Spain

Start date: May 15, 2023

Completion date: July 2025

Lead sponsor:
Agency: Pathalys Pharma
Agency class: Industry

Collaborator:
Agency: Launch Therapeutics
Agency class: Other

Source: Pathalys Pharma

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05836220