Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-1

Trial Title: Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-1

NCT ID: NCT05832931

Condition: Secondary Hyperparathyroidism
End-stage Kidney Disease (ESKD)

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: USA016-1

Address:
City: Pine Bluff
Zip: 71603-4921
Country: United States

Facility:
Name: Site Number: USA032-1

Address:
City: Anaheim
Zip: 92801-2817
Country: United States

Facility:
Name: Site Number: USA031-1

Address:
City: Beverly Hills
Zip: 90211-2921
Country: United States

Facility:
Name: Site Number: USA020-1

Address:
City: Fairfield
Zip: 94534
Country: United States

Facility:
Name: Site Number: USA023-1

Address:
City: Fullerton
Zip: 92835-3639
Country: United States

Facility:
Name: Site Number: USA030-1

Address:
City: Glendale
Zip: 91206-4015
Country: United States

Facility:
Name: Site Number: USA045-1

Address:
City: Oxnard
Zip: 93036-3075
Country: United States

Facility:
Name: Site Number: USA046-1

Address:
City: Riverside
Zip: 92505-3081
Country: United States

Facility:
Name: Site Number: USA035-1

Address:
City: Salinas
Zip: 93901-4446
Country: United States

Facility:
Name: Site Number: USA001-1

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

Facility:
Name: Site Number: USA021-1

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

Facility:
Name: Site Number: USA019-1

Address:
City: San Dimas
Zip: 91773-3537
Country: United States

Facility:
Name: Site Number: USA036-1

Address:
City: Whittier
Zip: 90606-3007
Country: United States

Facility:
Name: Site Number: USA018-1

Address:
City: Denver
Zip: 80210-5073
Country: United States

Facility:
Name: Site Number: USA003-1

Address:
City: Lone Tree
Zip: 80124-3191
Country: United States

Facility:
Name: Site Number: USA009-1

Address:
City: Hartford
Zip: 06112-1272
Country: United States

Facility:
Name: Site Number: USA042-1

Address:
City: Coral Gables
Zip: 33134-2049
Country: United States

Facility:
Name: Site Number: USA055-1

Address:
City: Coral Gables
Zip: 33134-2060
Country: United States

Facility:
Name: Site Number: USA034-1

Address:
City: Hollywood
Zip: 33024-2776
Country: United States

Facility:
Name: Site Number: USA053-1

Address:
City: Atlanta
Zip: 30342-1626
Country: United States

Facility:
Name: Site Number: USA013-1

Address:
City: Dalton
Zip: 30720
Country: United States

Facility:
Name: Site Number: USA027-1

Address:
City: Boise
Zip: 83706-1248
Country: United States

Facility:
Name: Site Number: USA007-1

Address:
City: Shelbyville
Zip: 46176-8591
Country: United States

Facility:
Name: Site Number: USA026-1

Address:
City: Baton Rouge
Zip: 70808-4791
Country: United States

Facility:
Name: Site Number: USA015-1

Address:
City: Columbus
Zip: 39705-2024
Country: United States

Facility:
Name: Site Number: USA028-1

Address:
City: Oxford
Zip: 38655
Country: United States

Facility:
Name: Site Number: USA022-1

Address:
City: Kansas City
Zip: 64111-2925
Country: United States

Facility:
Name: Site Number: USA017-1

Address:
City: Las Vegas
Zip: 89107-6100
Country: United States

Facility:
Name: Site Number: USA010-1

Address:
City: Jersey City
Zip: 07305
Country: United States

Facility:
Name: Site Number: USA008-1

Address:
City: Gallup
Zip: 87301-5611
Country: United States

Facility:
Name: Site Number: USA011-1

Address:
City: Bronx
Zip: 10461-2755
Country: United States

Facility:
Name: Site Number: USA039-1

Address:
City: Manhasset
Zip: 11030-3802
Country: United States

Facility:
Name: Site Number: USA052-1

Address:
City: Charlotte
Zip: 28277-9720
Country: United States

Facility:
Name: Site Number: USA043-1

Address:
City: Greenville
Zip: 27834-4300
Country: United States

Facility:
Name: Site Number: USA033-1

Address:
City: Winston-Salem
Zip: 27103-7154
Country: United States

Facility:
Name: Site Number: USA040-1

Address:
City: Spartanburg
Zip: 29301-5085
Country: United States

Facility:
Name: Site Number: USA049-1

Address:
City: Knoxville
Zip: 37924-3606
Country: United States

Facility:
Name: Site Number: USA037-1

Address:
City: Arlington
Zip: 76015-2363
Country: United States

Facility:
Name: Site Number: USA024-1

Address:
City: Austin
Zip: 78751-3014
Country: United States

Facility:
Name: Site Number: USA056-1

Address:
City: Fort Worth
Zip: 76110-1865
Country: United States

Facility:
Name: Site Number: USA014-1

Address:
City: Houston
Zip: 77054-3835
Country: United States

Facility:
Name: Site Number: USA012-1

Address:
City: Houston
Zip: 77074-1802
Country: United States

Facility:
Name: Site Number: USA025-1

Address:
City: McAllen
Zip: 78503-1251
Country: United States

Facility:
Name: Site Number: USA029-1

Address:
City: San Antonio
Zip: 78202-2916
Country: United States

Facility:
Name: Site Number: USA005-1

Address:
City: San Antonio
Zip: 78229-4605
Country: United States

Facility:
Name: Site Number: USA004-1

Address:
City: San Antonio
Zip: 78251-4498
Country: United States

Facility:
Name: Site Number: USA002-1

Address:
City: The Woodlands
Zip: 77384-8042
Country: United States

Facility:
Name: Site Number: USA006-1

Address:
City: Norfolk
Zip: 23504-2303
Country: United States

Facility:
Name: Site Number: USA050-1

Address:
City: Wauwatosa
Zip: 53226-4339
Country: United States

Facility:
Name: Site Number: BGR003-1

Address:
City: Sofia
Zip: 1309
Country: Bulgaria

Facility:
Name: Site Number: BGR004-1

Address:
City: Sofia
Zip: 1431
Country: Bulgaria

Facility:
Name: Site Number: BGR002-1

Address:
City: Blagoevgrad
Zip: 2700
Country: Bulgaria

Facility:
Name: Site Number: BGR001-1

Address:
City: Plovdiv
Zip: 4002
Country: Bulgaria

Facility:
Name: Site Number: POL005-1

Address:
City: Oleśnica
Zip: 56-400
Country: Poland

Facility:
Name: Site Number: POL002-1

Address:
City: Zyrardow
Zip: 96-300
Country: Poland

Facility:
Name: Site Number: PRT003-1

Address:
City: Portimão
Zip: 8500-311
Country: Portugal

Facility:
Name: Site Number: PRT001-1

Address:
City: Carregado
Zip: 2580-588
Country: Portugal

Facility:
Name: Site Number: PRT002-1

Address:
City: Forte Da Casa
Zip: 2625-384
Country: Portugal

Facility:
Name: Site Number: SRB001-1

Address:
City: Belgrade
Zip: 11000
Country: Serbia

Facility:
Name: Site Number: SRB003-1

Address:
City: Kragujevac
Zip: 34000
Country: Serbia

Facility:
Name: Site Number: SRB005-1

Address:
City: Novi Sad
Zip: 21000
Country: Serbia

Facility:
Name: Site Number: SRB002-1

Address:
City: Zaječar
Zip: 19000
Country: Serbia

Facility:
Name: Site Number: ESP001-1

Address:
City: Lleida
Zip: 25198
Country: Spain

Facility:
Name: Site Number: ESP004-1

Address:
City: Madrid
Zip: 28034
Country: Spain

Facility:
Name: Site Number: ESP005-1

Address:
City: Madrid
Zip: 28046
Country: Spain

Facility:
Name: Site Number: ESP003-1

Address:
City: Pamplona
Zip: 31008
Country: Spain

Facility:
Name: Site Number: ESP006-1

Address:
City: Sevilla
Zip: 41009
Country: Spain

Facility:
Name: Site Number: ESP002-1

Address:
City: Valencia
Zip: 46014
Country: Spain

Start date: April 28, 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/NCT05832931