PLS240 for Secondary Hyperparathyroidism

(PATH-2 Trial)

Recruiting at 75 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, 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

412 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of certain medications, like active Vitamin D sterols, phosphate binders, and calcium supplements, throughout the study. If you're taking these, you won't need to stop, but you must keep the dose stable.

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

Research on vitamin D analogues, like CTA018/MT2832, shows they can effectively lower parathyroid hormone levels without affecting calcium or phosphorus levels, suggesting potential benefits for secondary hyperparathyroidism treatment. ^{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. ^{3 6 7 8 9}

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.

Eligibility Criteria

Adults aged 18-80 on hemodialysis for end-stage kidney disease with secondary hyperparathyroidism can join. They must have specific levels of parathyroid hormone and calcium, stable doses of certain medications, and agree to contraception if applicable. Excluded are those with primary hyperparathyroidism, recent heart issues or seizures, certain cancers within the last two years, uncontrolled diabetes or hypertension, and anyone who's been in other drug trials recently.

Inclusion Criteria

I am a woman who cannot become pregnant or will avoid pregnancy during the study.

Voluntarily given written informed consent to participate in this study

I am a man willing to use effective birth control and not donate sperm during and for 2 weeks after treatment.

Exclusion Criteria

Continues to meet Exclusion Criterion #5

I or my family have a history of long QT syndrome.

I am scheduled for a kidney transplant from a living donor during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Double-Blind Treatment

Participants are randomly assigned to 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

• Placebo
• PLS240

Trial Overview The trial tests PLS240's effectiveness and safety against a placebo in patients undergoing hemodialysis due to severe kidney disease causing high parathyroid hormone levels. It has two phases: a double-blind phase where participants get either PLS240 or placebo randomly for 27 weeks; followed by an open-label extension where all receive PLS240 for another 26 weeks.

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. Ireland pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

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]