Encaleret for Hypoparathyroidism

Overseen By Iris R Hartley, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)

Must not be taking: PTH analogs, Encaleret

Disqualifiers: Hypocalcemic seizure, Cardiac disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 3

Duration: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, encaleret, for treating postsurgical hypoparathyroidism (PSH), a condition where low calcium levels occur after neck surgery. Current treatments can cause kidney issues, so researchers seek a better solution. Participants should have PSH, meaning low blood calcium after neck surgery, and manage their calcium levels with conventional treatments. The trial involves taking encaleret for five days, with close monitoring of blood and urine. This offers those with PSH a chance to find a more effective treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. If you are on thiazide diuretics or strong CYP3A4 inhibitors, you must stop them for a specific time before starting the study drug and remain off them during the trial. Also, if you take magnesium or potassium citrate supplements, you should stop them two days before the study begins.

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

Research has shown that encaleret has been studied for its safety and effectiveness. In previous studies, encaleret consistently helped maintain calcium levels for 18 months, indicating it is well-tolerated by participants. Another study found that encaleret improved calcium levels without major problems, supporting its safety.

These studies focused on a condition called autosomal dominant hypocalcemia type 1, but the safety information helps researchers understand how encaleret might work for people with postsurgical hypoparathyroidism (PSH). Ongoing research will provide more specific safety details for those with PSH. Overall, current evidence suggests that encaleret is a promising and well-tolerated option for managing calcium levels. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Encaleret is unique because it offers a new approach for treating hypoparathyroidism, a condition traditionally managed with calcium and active vitamin D supplements. Unlike these standard treatments, which primarily address symptoms, Encaleret directly targets the underlying cause by modulating calcium and parathyroid hormone levels. Researchers are excited about Encaleret because it has the potential to provide more stable control of calcium levels, reducing fluctuations and improving patients' quality of life. Additionally, its twice-daily oral administration could offer a convenient alternative to frequent monitoring and adjustments required with current therapies.

What evidence suggests that encaleret might be an effective treatment for hypoparathyroidism?

Research has shown that encaleret, the investigational treatment in this trial, can effectively increase blood calcium levels. In one study, patients taking encaleret experienced an average calcium level increase of 0.82 mg/dL, marking a significant improvement. Additionally, 76% of patients achieved normal calcium levels in both blood and urine. These results are promising for using encaleret to treat conditions like postsurgical hypoparathyroidism, where maintaining stable calcium levels is crucial. Early findings suggest that encaleret might be a better option than current treatments, which can sometimes lead to kidney problems. ^{1 2 3 4 6}

Who Is on the Research Team?

Iris R Hartley, M.D.

Principal Investigator

National Institute of Dental and Craniofacial Research (NIDCR)

Are You a Good Fit for This Trial?

Adults with postsurgical hypoparathyroidism (PSH) can join this study. They must have stable blood calcium levels on current treatments, a BMI between 18.5 and <39 kg/m2, and normal or managed thyroid function. Pregnant women, those at childbearing age not using contraception, people with recent substance dependency, certain heart conditions, liver issues or severe kidney problems cannot participate.

Inclusion Criteria

Participants must be able to understand and sign a written informed consent form, obtained prior to initiation of study procedures

Body mass index (BMI) must be between 18.5 to < 39 kg/m2

I can stop taking strong CYP3A4 inhibitors before starting the study treatment.

Exclusion Criteria

My liver isn't working well.

Unwillingness to refrain from blood donation within specific timeframes

I have had a seizure caused by low calcium in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 days

1 visit (in-person)

Treatment

Participants receive encaleret by mouth twice a day for 5 days while staying in the clinic

7 days

1 visit (in-patient stay)

Follow-up

Participants have follow-up blood tests and phone calls to monitor safety and effectiveness after treatment

1 week

1 visit (in-person), 3 phone calls

What Are the Treatments Tested in This Trial?

Interventions

• Encaleret

Trial Overview

The trial is testing encaleret for PSH patients to manage their blood calcium without causing kidney issues. Participants will take encaleret orally twice daily for five days during a week-long clinic stay where they'll undergo frequent blood tests and urine collection followed by follow-up checks.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

All participants given 5 days of encaleret twice daily

Who Is Running the Clinical Trial?

National Institute of Dental and Craniofacial Research (NIDCR)

Lead Sponsor

Trials

312

Recruited

853,000+

Published Research Related to This Trial

In a study involving 24 adults with postsurgical chronic hypoparathyroidism, calcium citrate (Ca-Cit) was found to significantly reduce urinary oxalate excretion compared to calcium carbonate (CaCO3), which may lower the risk of kidney stones (nephrolithiasis).

Both Ca-Cit and CaCO3 maintained similar serum calcium and phosphorus levels, but Ca-Cit was associated with less constipation, suggesting it may be a better option for patients who have difficulty tolerating CaCO3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial. Naciu, AM., Tabacco, G., Bilezikian, JP., et al.[2023]

Cinacalcet was successfully used to manage a newborn with neonatal severe hyperparathyroidism (NSHPT) caused by a genetic mutation, effectively controlling calcium, phosphorus, and parathyroid hormone levels.

The treatment was well-tolerated, showing no side effects over the course of one year, suggesting that cinacalcet could be a safe alternative to traditional treatments for NSHPT in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cinacalcet therapy in an infant with an R185Q calcium-sensing receptor mutation causing hyperparathyroidism: a case report and review of the literature. Forman, TE., Niemi, AK., Prahalad, P., et al.[2021]

In a 12-month study involving 14 adults with chronic hypoparathyroidism, treatment with rhPTH (1-84) led to normalization of serum calcium levels, allowing 61.5% of patients to discontinue calcium supplements and 69.2% to stop calcitriol, indicating its efficacy as a hormonal replacement therapy.

The treatment was found to be safe, with no severe adverse events reported, and renal function remained normal throughout the study, suggesting that rhPTH (1-84) is a viable option for patients not adequately controlled by conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter retro-prospective observational study on chronic hypoparathyroidism and rhPTH (1-84) treatment. Marcucci, G., Beccuti, G., Carosi, G., et al.[2022]

The Hypoparathyroid Patient Questionnaire (HPQ 40/28) effectively identified and quantified specific symptoms in patients with postsurgical hypoparathyroidism (HypoPT), highlighting significant complaints such as pain, cramps, and neurovegetative symptoms.

The calcium-phosphate product (CPP) was found to be the main contributor to the severity of symptoms in HypoPT patients, correlating with various complaints including loss of vitality and memory problems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantification of Symptom Load by a Disease-Specific Questionnaire HPQ 28 and Analysis of Associated Biochemical Parameters in Patients With Postsurgical Hypoparathyroidism. Wilde, D., Wilken, L., Stamm, B., et al.[2020]

The calcilytic AXT914 effectively increased serum parathyroid hormone (PTH) and calcium levels while decreasing phosphorus levels and urinary calcium excretion in rat models of postsurgical hypoparathyroidism, indicating its potential as a treatment option.

AXT914 not only corrected calcium and phosphorus imbalances but also improved the functional recovery of autotransplanted parathyroid tissues, suggesting a beneficial mechanism of action in managing postsurgical hypoparathyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Therapeutic Approach Using a Calcilytic (AXT914) for Postsurgical Hypoparathyroidism in Female Rats. Lim, YS., You, BH., Kim, HB., et al.[2021]

Citations

1.

investor.bridgebio.com

investor.bridgebio.com/news/news-details/2025/BridgeBio-Reports-Positive-Phase-3-Topline-Results-for-Encaleret-in-Patients-with-Autosomal-Dominant-Hypocalcemia-Type-1/default.aspx

News Details

Encaleret achieved a mean increase in change from baseline of corrected calcium by 0.82 mg/dL from Week 4 to Week 24 (p<0.0001); Encaleret ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05680818

NCT05680818 | Efficacy and Safety of Encaleret ...

The primary purpose of the study is to understand the effectiveness, safety, and tolerability of encaleret when compared to standard of care (SoC) treatment ...

3.

empr.com

empr.com/news/promising-results-for-encaleret-in-rare-calcium-disorder/

Promising Results for Encaleret in Rare Calcium Disorder

Findings showed 76% of patients treated with encaleret met the primary endpoint, achieving both blood and urine calcium levels within the target ...

4.

academic.oup.com

academic.oup.com/jes/article/7/Supplement_1/bvad114.561/7289952

Results From A Phase 2 Study Over 18 Months Of Encaleret ...

The consistent and sustained results from over 18 months of outpatient encaleret treatment are clinically meaningful and support Phase 3 ...

5.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/29/NCT04581629/Prot_000.pdf

CLTX-305-201 NIH 20-D-0122 IND Nu

Effective doses of CLTX-305 (encaleret) for patients with ADH1 cannot be determined without execution of a specifically designed clinical trial.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10616810/

Efficacy and Safety of Encaleret in Autosomal Dominant ...

In our study, encaleret appeared to restore physiologic mineral homeostasis in 13 participants with ADH1. This molecularly targeted approach, pending further ...