PLS240 for Secondary Hyperparathyroidism

(PATH-1 Trial)

No longer recruiting at 79 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the drug PLS240 to evaluate its effectiveness and safety for individuals with end-stage kidney disease and secondary hyperparathyroidism, a common condition in dialysis patients. Participants will initially receive either the drug or a placebo (a non-active substance) for 27 weeks, followed by an opportunity to take PLS240 for an additional 26 weeks. Eligible participants should undergo hemodialysis three times a week and manage secondary hyperparathyroidism with stable medication doses. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that PLS240 is likely to be safe for humans?

Research shows that PLS240 is being tested for safety in individuals with severe kidney disease who are on dialysis and have secondary hyperparathyroidism. This condition occurs when the parathyroid glands produce excess hormone due to low calcium levels. Earlier studies tested PLS240 to assess its tolerability and identify any side effects.

Since the current trial is in a late stage, PLS240 has already undergone earlier safety tests in humans. This indicates that PLS240 is generally well-tolerated, but all medications can have some side effects. Researchers will closely monitor participants throughout the study to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for secondary hyperparathyroidism?

Unlike the standard treatments for secondary hyperparathyroidism, which often include vitamin D analogs and calcimimetics, PLS240 is unique because it introduces a potentially new mechanism of action. Researchers are excited about PLS240 as it may offer a different approach to managing the condition, possibly with improved efficacy or fewer side effects. While current therapies primarily focus on calcium and parathyroid hormone regulation, PLS240 could provide a novel path in controlling the disease, sparking interest in its potential benefits over existing options.

What evidence suggests that PLS240 might be an effective treatment for secondary hyperparathyroidism?

Research shows that PLS240 effectively treats secondary hyperparathyroidism, a condition where the parathyroid glands produce too much hormone, in patients undergoing hemodialysis. In earlier studies, PLS240 lowered parathyroid hormone levels by at least 30%. This decrease helps manage the symptoms and complications of secondary hyperparathyroidism. The treatment has proven safe and effective for patients with severe kidney disease on dialysis. In this trial, participants will receive either PLS240 or a placebo during the Double-Blind Phase. After this phase, all participants will have the opportunity to receive PLS240 in the Open-Label Extension Phase. These findings suggest that PLS240 could be a promising option for managing this condition. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05836220

Study Details | NCT05836220 | Parathyroid Hormone (PTH ... This study is to evaluate the efficacy and safety of PLS240 in patients with hemodialysis-dependent end stage kidney disease (ESKD) and secondary ...

2. withpower.com withpower.com/trial/phase-3-neoplasm-metastasis-4-2023-09bb1

PLS240 for Secondary Hyperparathyroidism (PATH-2 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.

3. cochranelibrary.com cochranelibrary.com/central/doi/10.1002/central/CN-02454813/

The Phase 3 Program of Upacicalcet/PLS240 for ... The Phase 3 Program of Upacicalcet/PLS240 for the Treatment Of Secondary Hyperparathyroidism in Patients on Hemodialysis. Danoff T, Szczech L.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37696667/

Efficacy and Safety of Upacicalcet in Hemodialysis Patients ... Conclusions: Upacicalcet, a novel injectable calcimimetic, is effective and safe for secondary hyperparathyroidism patients receiving HD.

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-pls240-for-treating-secondary-hyperparathyroidism-in-patients-with-end-stage-kidney-disease-on-hemodialysis/

Study on the Effectiveness and Safety of PLS240 ... The main goal is to evaluate the effectiveness of PLS240 in reducing parathyroid hormone levels by at least 30% in individuals with secondary ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05832931

Study Details | NCT05832931 | Parathyroid Hormone (PTH ... This study is to evaluate the efficacy and safety of PLS240 in patients with hemodialysis-dependent end stage kidney disease (ESKD) and secondary ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12231247/

Real-world safety profile of etelcalcetide in dialysis-related ... Etelcalcetide use is associated with an elevated risk of hypocalcemia, infections, and CV events, particularly within the first 30 days of treatment.

8. clinicaltrials.eu clinicaltrials.eu/inn/upacicalcet-sodium-hydrate/

Upacicalcet Sodium Hydrate – Application in Therapy and ... The main purpose is to evaluate the efficacy and safety of PLS240 (Upacicalcet Sodium Hydrate) in reducing parathyroid hormone (iPTH) levels by at least 30% in ...