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-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pathalys Pharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Hormonal diseases [C19]

Trial duration

9 Nov 2023 → 28 Jul 2025

Decision date (initial)

2023-10-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pathalys Pharma, Inc.

External identifiers

EU CT number

2023-504338-24-00

ClinicalTrials.gov

NCT05832931

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Double-blind phase: To assess the efficacy of PLS240 compared to placebo in reducing iPTH by ≥30% in participants with SHPT undergoing chronic hemodialysis.
Open-Label phase: To assess the long-term safety of PLS240 in participants who have completed the safety follow-up visit of the Double-Blind Phase.

Secondary objectives 7

1. To assess the efficacy of PLS240 compared to placebo in reducing iPTH by ≥50%
2. Estimate the proportion of participants with a mean iPTH in the target range of 150-300 pg/mL during the Efficacy Assessment Period (EAP) (Weeks 22-27).
3. Estimate the time course of change of iPTH during the course of the study.
4. Estimate the time course of changes in albumin-corrected serum calcium (cCa), serum phosphate (P) and their mathematical product.
5. To assess the efficacy of PLS240 compared to placebo in reducing iPTH by ≥30% in participants who did not have an increase in active Vitamin D sterol dose
6. Describe the pharmacokinetics (PK) of PLS240.
7. Safety and tolerability

Conditions and MedDRA coding

ESKD participants with history of secondary hyperparathyroidism (SHPT) undergoing maintenance hemodialysis

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

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 screening iPTH must be ≥450 pg/mL on two measurements performed at 2 visits at least 1 week apart. Only one (1) repeat iPTH is allowed and must be 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.
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.
10. 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.
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
13. 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: 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 28

1. 1. Diagnosis of primary hyperparathyroidism
2. 9. Clinically significant abnormalities on screening laboratory tests (may repeat abnormal laboratory tests as defined in Ssection 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
3. 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 ICF or otherwise unstable in the judgment of the investigator
4. 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).
5. 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
6. 13. History of New York Heart Association (NYHA) Functional Class 3 or 4 heart failure (see Appendix 2)
7. 14. History of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 4 months prior to signing the ICF.
8. 15. Stroke (cerebral infarction or cerebral hemorrhage) within 6 months prior to signing the ICF
9. 16. Participant is receiving treatment for a seizure disorder or has a history of a seizure within 12 weeks prior signing the ICF
10. 17. Poorly controlled diabetes mellitus, in the judgment of the investigator or sub-investigator
11. 18. 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
12. 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.
13. 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)
14. 20. History of symptomatic ventricular dysrhythmias or Torsade de Pointes.
15. 21. History of or family history of long QT syndrome
16. 22. QTcF >500msec on screening ECG
17. 23. Pregnant or breast feeding
18. 24. Prior exposure or hypersensitivity to PLS240 or any of its components
19. 25. Current, recent, or suspected infection with SARS-CoV-2/COVID-19 within 4 weeks prior to signing the ICF
20. 26. In the opinion of the investigator any disorder that would interfere with understanding and giving informed consent, or compliance with protocol requirements
21. 27. 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: In the opinion of the investigator continuation into the Open-Label Extension Phase is not considered safe and/or feasible
22. 28. Continues to meet Exclusion Criterion #5
23. 3. History of parathyroid intervention including parathyroidectomy (PTx) and/or percutaneous ethanol injection therapy (PEIT) within 26 weeks before signing the ICF.
24. 4. Treatment with any prohibited medication as defined in protocol Section 8.3.1.
25. 5. Anticipated or scheduled parathyroidectomy during the study period.
26. 6. Planned living-related or living-unrelated kidney transplant during the study period.
27. 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
28. 8. 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. The proportion of participants with a ≥30% decrease in mean iPTH during the Efficacy Assessment Period (EAP, Weeks 22 - 27) relative to the mean baseline iPTH (all Active Screening and predose Day 1 iPTH values).
2. Open-Label Phase • Safety clinical laboratory tests, vital signs, ECG, AEs, and physical exams "
3. Open-Label Phase • Proportion of participants with a cCa <7.5 mg/dL, and the proportion of participants with a cCa <8.3 mg/dL

Secondary endpoints 9

1. • The proportion of participants with a ≥50% decrease in mean iPTH during the EAP (Weeks 22 - 27) relative to the mean baseline iPTH (all Active Screening and predose Day 1 iPTH values).
2. The proportion of participants with a mean iPTH during the EAP (Weeks 22 - 27) ≥150 pg/mL but ≤300 pg/mL.
3. The percentage change from baseline in iPTH during the course of the study (weekly iPTH values).
4. The absolute and percentage changes in serum cCa and serum P levels and their mathematical product
5. •The proportion of participants who did not have an increase in Active Vitamin D sterol dose during the double blind phasewith a ≥30% reductionin mean iPTH during the EAP relative to mean baseline iPTH
6. Cmax and AUC as data permit.
7. Removal rate by dialysis.
8. Safety clinical laboratory tests, ECGs, vital signs, AEs, AEs leading to modification of dose or frequency of calcium supplements or phosphate binders, and physical exams
9. Proportion of participants with a cCa <7.5 mg/dL, and proportion of participants with a cCa <8.3 mg/dL

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pathalys Pharma Inc.

Sponsor organisation

Pathalys Pharma Inc.

Address

4000 Center At North Hills Street

City

Raleigh

Postcode

27609-7093

Country

United States

Scientific contact point

Organisation

Pathalys Pharma Inc.

Contact name

Bastian Dehmel

Public contact point

Organisation

Pathalys Pharma Inc.

Contact name

Bastian Dehmel

Third parties 8

Locations

4 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications