What is the mechanism of action of this treatment?

Common treatments for Secondary Hyperparathyroidism (SHPT) work by modulating parathyroid gland activity to control PTH secretion, which is crucial for preventing complications like bone resorption and cardiovascular issues. PLS240, for example, is designed to reduce PTH secretion directly. Calcimimetics increase the sensitivity of calcium-sensing receptors on the parathyroid glands, thereby lowering PTH levels. Vitamin D analogs and phosphate binders help manage the mineral imbalances that contribute to elevated PTH, providing a comprehensive approach to treating SHPT.

What side effects are associated with this type of intervention?

Common treatments for secondary hyperparathyroidism that modulate parathyroid gland activity include calcimimetics (e.g., cinacalcet) and vitamin D analogs. Calcimimetics can cause side effects such as hypocalcemia, nausea, vomiting, and gastrointestinal discomfort. Vitamin D analogs may lead to hypercalcemia, hyperphosphatemia, and an increased risk of vascular calcification. Both types of treatments require careful monitoring of calcium and phosphate levels to mitigate these risks.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Secondary Hyperparathyroidism (SHPT) in patients with chronic kidney disease on dialysis. These include calcimimetics like cinacalcet, which increases the sensitivity of the calcium-sensing receptors on the parathyroid gland, thereby reducing PTH secretion. Another approved drug is etelcalcetide, an intravenous calcimimetic that also modulates parathyroid gland activity to control PTH levels. These treatments aim to manage the elevated PTH levels associated with SHPT, similar to the investigational drug PLS240 being studied in the trial.

What other types of research exist?

Promising novel alternatives to PLS240 for treating secondary hyperparathyroidism in 2024 include: 1) Etelcalcetide, a calcimimetic agent that activates calcium-sensing receptors on parathyroid cells, reducing PTH secretion. 2) Evocalcet, another calcimimetic with a similar mechanism of action but potentially fewer side effects. 3) Extended-release formulations of existing calcimimetics, which may improve patient compliance and outcomes. These alternatives are supported by clinical trials and ongoing research.

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Calcimimetic Agent

PLS240 for Secondary Hyperparathyroidism (PATH-2 Trial)

Phase 3

Waitlist Available

Research Sponsored by Pathalys Pharma

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Prescribed hemodialysis for 3 times per week

Must not have

History of or family history of long QT syndrome

Planned living-related or living-unrelated kidney transplant during the study period

Timeline

Screening 3 weeks

Treatment Varies

Follow Up each visit from screening through week 27

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While the side effects of PLS240 aren't specified here, similar drugs may cause issues like nausea, dizziness, bone pain or fractures due to changes in calcium levels. There could also be reactions at injection sites and potential impacts on blood pressure.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am on hemodialysis 3 times a week.

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I am between 18 and 80 years old.

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I have finished all treatments and safety checks from the earlier blind study phase.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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My blood pressure has been very high during dialysis sessions.

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I have had heart rhythm problems or Torsade de Pointes.

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I haven't had COVID-19 in the last 4 weeks.

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I have been diagnosed with primary hyperparathyroidism.

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My parathyroid hormone levels were above 1500 pg/mL at least twice before dialysis.

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

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I am scheduled for or might have a parathyroid gland surgery.

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I have severe heart failure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ each visit from screening through week 27

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~each visit from screening through week 27

This trial's timeline: 3 weeks for screening, Varies for treatment, and each visit from screening through week 27 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

The proportion of PLS240 treated participants compared to the portion of placebo treated participants with a ≥30% decrease in mean iPTH

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Open-Label Extension Phase PLS240Experimental Treatment1 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 PLS240Experimental Treatment1 Intervention

Group III: Double-Blind Phase PlaceboPlacebo Group1 Intervention

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Secondary Hyperparathyroidism (SHPT) work by modulating parathyroid gland activity to control PTH secretion, which is crucial for preventing complications like bone resorption and cardiovascular issues. PLS240, for example, is designed to reduce PTH secretion directly. Calcimimetics increase the sensitivity of calcium-sensing receptors on the parathyroid glands, thereby lowering PTH levels. Vitamin D analogs and phosphate binders help manage the mineral imbalances that contribute to elevated PTH, providing a comprehensive approach to treating SHPT.