Parathyroid Hormone (PTH) Attenuation Trial in Hemodialysis-1

NCT05832931 | Completed Phase 3 FDA Drug

• 2 other identifiers: PP30022023-504338-24
• Study Type: interventional
• Target: 362
• Locations: 6 countries
• Sites: 68

Brief 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.

Conditions

Secondary Hyperparathyroidism; End-stage Kidney Disease (ESKD)

Outcome Measures

Primary Outcomes (5)

• Double-Blind Phase: Proportion of PLS240 treated participants compared to placebo treated participants with a ≥30% decrease in mean iPTH

  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

• Open-Label Phase: Proportion of participants with a corrected serum calcium (cCa) <7.5 mg/dL

  up to week 28

• Open-Label Phase: Proportion of participants with a corrected serum calcium (cCa) <8.3 mg/dL

  up to week 28

• Open-Label Phase: Number of Adverse Events (AEs)

  up to week 28

• Open-Label Phase: Number of Serious Adverse Events (SAEs)

  up to week 28

Study Arms (3)

Double-Blind Phase PLS240

EXPERIMENTAL

Drug: PLS240

Double-Blind Phase Placebo

PLACEBO COMPARATOR

Drug: Placebo

Open-Label Extension Phase PLS240

EXPERIMENTAL

After completion of the Double-Blind Phase, all participants will have the opportunity to enroll in the 26 week Open-Label extension, where they will receive PLS240.

Drug: Open-Label Extension PLS240

Interventions

PLS240 DRUG

Participants will receive intravenous (IV) PLS240 three times per week for 27 weeks.

Double-Blind Phase PLS240

Placebo DRUG

Participants will receive intravenous (IV) placebo, containing no active drug, three times per week for 27 weeks.

Double-Blind Phase Placebo

Open-Label Extension PLS240 DRUG

Participants will receive intravenous (IV) PLS240 three times per week for a maximum of 26 weeks.

Open-Label Extension Phase PLS240

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 - 80 years at time of informed consent.
• 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.
• 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.
• 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.
• Dialysate calcium concentration ≥2.5 mEq/L (1.25 mmol/L) and stable for at least 4 weeks prior to signing the ICF.
• 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.
• 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.
• 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.
• 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.
• 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.
• Voluntarily given written informed consent to participate in this study.
• Agrees to not participate in another study of an investigational agent during the study
• Have successfully completed the course of treatment and final safety follow-up visit of the Double-Blind Phase.
• Voluntarily given written informed consent to participate in the Open-Label Extension Phase of the study.

You may not qualify if:

• Diagnosis of primary hyperparathyroidism.
• 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.
• History of parathyroid intervention including parathyroidectomy (PTx) and percutaneous ethanol injection therapy (PEIT) within 26 weeks before signing the ICF.
• Treatment with any prohibited medication as defined in Section 8.3.1.
• Anticipated or scheduled parathyroidectomy during the study period.
• Planned living-related or living-unrelated kidney transplant during the study period.
• 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.
• 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).
• Clinically significant abnormalities on screening laboratory tests (may repeat abnormal laboratory tests) according to the Investigator including but not limited to the following:
• Serum albumin ≤3.0 g/dL
• Serum magnesium \<1.5 mg/dL
• Serum P \>8.0 mg/dL
• Hemoglobin \<8.5 g/dL
• Platelet count \<100,000 x106/L
• 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.

Sponsors & Collaborators

• Pathalys Pharma: lead
• Launch Therapeutics: collaborator

Study Sites (68)

Site Number: USA016-1

Pine Bluff, Arkansas, 71603-4921, United States

Location

Site Number: USA032-1

Anaheim, California, 92801-2817, United States

Location

Site Number: USA031-1

Beverly Hills, California, 90211-2921, United States

Location

Site Number: USA020-1

Fairfield, California, 94534, United States

Location

Site Number: USA023-1

Fullerton, California, 92835-3639, United States

Location

Site Number: USA030-1

Glendale, California, 91206-4015, United States

Location

Site Number: USA045-1

Oxnard, California, 93036-3075, United States

Location

Site Number: USA046-1

Riverside, California, 92505-3081, United States

Location

Site Number: USA035-1

Salinas, California, 93901-4446, United States

Location

Site Number: USA001-1

San Diego, California, 92111-3636, United States

Location

Site Number: USA021-1

San Diego, California, 92111-3636, United States

Location

Site Number: USA019-1

San Dimas, California, 91773-3537, United States

Location

Site Number: USA036-1

Whittier, California, 90606-3007, United States

Location

Site Number: USA018-1

Denver, Colorado, 80210-5073, United States

Location

Site Number: USA003-1

Lone Tree, Colorado, 80124-3191, United States

Location

Site Number: USA009-1

Hartford, Connecticut, 06112-1272, United States

Location

Site Number: USA042-1

Coral Gables, Florida, 33134-2049, United States

Location

Site Number: USA055-1

Coral Gables, Florida, 33134-2060, United States

Location

Site Number: USA034-1

Hollywood, Florida, 33024-2776, United States

Location

Site Number: USA053-1

Atlanta, Georgia, 30342-1626, United States

Location

Site Number: USA013-1

Dalton, Georgia, 30720, United States

Location

Site Number: USA027-1

Boise, Idaho, 83706-1248, United States

Location

Site Number: USA007-1

Shelbyville, Indiana, 46176-8591, United States

Location

Site Number: USA026-1

Baton Rouge, Louisiana, 70808-4791, United States

Location

Site Number: USA015-1

Columbus, Mississippi, 39705-2024, United States

Location

Site Number: USA028-1

Oxford, Mississippi, 38655, United States

Location

Site Number: USA022-1

Kansas City, Missouri, 64111-2925, United States

Location

Site Number: USA017-1

Las Vegas, Nevada, 89107-6100, United States

Location

Site Number: USA010-1

Jersey City, New Jersey, 07305, United States

Location

Site Number: USA008-1

Gallup, New Mexico, 87301-5611, United States

Location

Site Number: USA039-1

Manhasset, New York, 11030-3802, United States

Location

Site Number: USA011-1

The Bronx, New York, 10461-2755, United States

Location

Site Number: USA052-1

Charlotte, North Carolina, 28277-9720, United States

Location

Site Number: USA043-1

Greenville, North Carolina, 27834-4300, United States

Location

Site Number: USA033-1

Winston-Salem, North Carolina, 27103-7154, United States

Location

Site Number: USA040-1

Spartanburg, South Carolina, 29301-5085, United States

Location

Site Number: USA049-1

Knoxville, Tennessee, 37924-3606, United States

Location

Site Number: USA037-1

Arlington, Texas, 76015-2363, United States

Location

Site Number: USA024-1

Austin, Texas, 78751-3014, United States

Location

Site Number: USA056-1

Fort Worth, Texas, 76110-1865, United States

Location

Site Number: USA014-1

Houston, Texas, 77054-3835, United States

Location

Site Number: USA012-1

Houston, Texas, 77074-1802, United States

Location

Site Number: USA025-1

McAllen, Texas, 78503-1251, United States

Location

Site Number: USA029-1

San Antonio, Texas, 78202-2916, United States

Location

Site Number: USA005-1

San Antonio, Texas, 78229-4605, United States

Location

Site Number: USA004-1

San Antonio, Texas, 78251-4498, United States

Location

Site Number: USA002-1

The Woodlands, Texas, 77384-8042, United States

Location

Site Number: USA006-1

Norfolk, Virginia, 23504-2303, United States

Location

Site Number: USA050-1

Wauwatosa, Wisconsin, 53226-4339, United States

Location

Site Number: BGR003-1

Sofia, Sofia-Grad, 1309, Bulgaria

Location

Site Number: BGR004-1

Sofia, Sofia-Grad, 1431, Bulgaria

Location

Site Number: BGR002-1

Blagoevgrad, 2700, Bulgaria

Location

Site Number: BGR001-1

Plovdiv, 4002, Bulgaria

Location

Site Number: POL005-1

Oleśnica, Lower Silesian Voivodeship, 56-400, Poland

Location

Site Number: POL002-1

Żyrardów, Masovian Voivodeship, 96-300, Poland

Location

Site Number: PRT003-1

Portimão, Faro District, 8500-311, Portugal

Location

Site Number: PRT001-1

Carregado, Lisbon District, 2580-588, Portugal

Location

Site Number: PRT002-1

Forte Da Casa, Lisbon District, 2625-384, Portugal

Location

Site Number: SRB001-1

Belgrade, 11000, Serbia

Location

Site Number: SRB003-1

Kragujevac, 34000, Serbia

Location

Site Number: SRB005-1

Novi Sad, 21000, Serbia

Location

Site Number: SRB002-1

Zaječar, 19000, Serbia

Location

Site Number: ESP001-1

Lleida, 25198, Spain

Location

Site Number: ESP004-1

Madrid, 28034, Spain

Location

Site Number: ESP005-1

Madrid, 28046, Spain

Location

Site Number: ESP003-1

Pamplona, 31008, Spain

Location

Site Number: ESP006-1

Seville, 41009, Spain

Location

Site Number: ESP002-1

Valencia, 46014, Spain

Location

MeSH Terms

Conditions

Hyperparathyroidism, Secondary; Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2023
• First Posted: April 27, 2023
• Study Start: April 28, 2023
• Primary Completion: July 28, 2025
• Study Completion: July 28, 2025
• Last Updated: September 9, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

PT (3); BU (4); SE (4); ES (6); US (49); PL (2)