PLS240 for Secondary Hyperparathyroidism

(PATH-1 Trial)

Recruiting at 76 trial locations

Overseen By Pathalys Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pathalys Pharma

Must be taking: Vitamin D sterols

Disqualifiers: Primary hyperparathyroidism, Parathyroid intervention, Unstable condition, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

362 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called PLS240 to help people with severe kidney disease who are on dialysis and have a related gland problem. The study will check if PLS240 can safely manage their condition by controlling certain hormones and minerals in their blood. Patients will be monitored over time.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications. However, if you are taking active Vitamin D sterols, phosphate binders, or calcium supplements, you must be on a stable dose before and during the study.

What evidence supports the effectiveness of the drug PLS240 for treating secondary hyperparathyroidism?

Research on vitamin D analogues, like those used in PLS240, shows they can effectively lower parathyroid hormone levels in conditions similar to secondary hyperparathyroidism, such as chronic kidney disease, without significantly affecting calcium or phosphorus levels. ^{1 2 3 4 5}

How does the drug PLS240 differ from other treatments for secondary hyperparathyroidism?

PLS240 may be unique in its approach by potentially targeting fibroblast growth factor-23 (FGF23), which is involved in phosphate regulation and is linked to secondary hyperparathyroidism. This focus on FGF23 could offer a novel mechanism compared to traditional treatments that primarily address calcium and vitamin D levels. ^{1 6 7 8 9}

Eligibility Criteria

Adults aged 18-80 on hemodialysis for end-stage kidney disease with secondary hyperparathyroidism can join. They must have stable vitamin D, phosphate binder, and calcium supplement doses, agree to contraception if applicable, and not be in other studies. Excluded are those with primary hyperparathyroidism, recent heart issues or strokes, uncontrolled diabetes or hypertension, certain ECG abnormalities, recent serious infections like COVID-19, or a history of malignancy within the last two years.

Inclusion Criteria

Voluntarily given written informed consent to participate in this 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: 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, Prescribed hemodialysis for 3 times per week, Continue to meet Inclusion Criteria 9, 10, and 12

I have been taking the same dose of calcium supplements for the last 2 months.

Exclusion Criteria

You have important irregularities in your screening blood tests, as determined by the doctor in charge of the study.

I have not had a stroke in the last 6 months.

I am being treated for seizures or had a seizure in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Double-Blind Treatment

Participants receive dose-titrated PLS240 or placebo for 27 weeks

27 weeks

Multiple visits (in-person)

Open-Label Extension

Participants receive dose-titrated PLS240 for an additional 26 weeks

26 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Open-Label Extension PLS240
• Placebo
• PLS240

Trial Overview The trial tests PLS240's effectiveness and safety against placebo in patients undergoing hemodialysis due to severe kidney disease complicated by secondary hyperparathyroidism. It has a double-blind phase (27 weeks) followed by an open-label extension (26 weeks), where all receive PLS240. Participants will undergo regular blood tests, ECGs and physical exams.

Participant Groups

Group I: Open-Label Extension Phase PLS240 Experimental Treatment 1 Intervention

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.

Group II: Double-Blind Phase PLS240 Experimental Treatment 1 Intervention

Group III: Double-Blind Phase Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Pathalys Pharma

Lead Sponsor

Trials

2

Recruited

770+

Launch Therapeutics

Collaborator

Trials

2

Recruited

770+

References

1. England pubmed.ncbi.nlm.nih.gov

Fibroblast growth factor 23, parathyroid hormone, and 1alpha,25-dihydroxyvitamin D in surgically treated primary hyperparathyroidism. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

Determinants for serum 1,25-dihydroxycholecalciferol in primary hyperparathyroidism. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Vitamin D analogues targeting CYP24 in chronic kidney disease. [2016]

4. Poland pubmed.ncbi.nlm.nih.gov

FGF23 and primary hyperparathyroidism: is there a link? [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Differential effects of 1,25-(OH)2D3 and 22-oxacalcitriol on phosphate and calcium metabolism. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Elevated FGF23 levels are associated with impaired calcium-mediated suppression of PTH in ESRD. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Serum fibroblast growth factor-23 levels predict the future refractory hyperparathyroidism in dialysis patients. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Fibroblast growth factor-23 in early chronic kidney disease: additional support in favor of a phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Molecular mechanisms of secondary hyperparathyroidism. [2019]