Encaleret for Hypocalcemia

(CALIBRATE Trial)

Recruiting at 29 trial locations

Overseen By Medical Information

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company

Must not be taking: Thiazides, Phosphate binders

Disqualifiers: Hypocalcemic seizure, Thyroid surgery, others

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

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: Unknown

67 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called encaleret for people with a rare genetic condition known as ADH1. ADH1 causes low calcium levels, and current treatments may not be effective or safe enough. Encaleret aims to help by balancing calcium levels in the blood.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. If you are on thiazide diuretics, phosphate binders, magnesium or potassium supplements, or potassium-sparing diuretics, you will need to discontinue them before starting the trial. There are specific timeframes for stopping these medications, such as at least 14 days for thiazides and at least one day for phosphate binders.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. If you are on thiazide diuretics, you must stop them at least 14 days before a specific visit. You also need to stop phosphate binders (except calcium salts), magnesium or potassium supplements, and potassium-sparing diuretics before starting the trial.

What data supports the effectiveness of the drug Encaleret for treating hypocalcemia?

Research on similar drugs like cinacalcet, which also targets the calcium sensing receptor, shows that it effectively lowers calcium levels in conditions with high calcium, suggesting that Encaleret might work similarly for hypocalcemia by adjusting calcium levels. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Encaleret for treating hypocalcemia?

Research on similar drugs like cinacalcet, which also targets the calcium sensing receptor, shows it can effectively lower calcium levels in conditions with high calcium, suggesting potential effectiveness for Encaleret in managing calcium levels. ^{1 2 3 4 5}

Is Encaleret safe for treating hypocalcemia?

The safety data for Encaleret specifically is not available in the provided research articles. However, similar treatments like cinacalcet and etelcalcetide, used for related conditions, have shown that hypocalcemia (low calcium levels) is a common side effect, but they are generally considered safe with careful monitoring. ^{6 7 8 9 10}

Is Encaleret safe for treating hypocalcemia?

The safety data for Encaleret specifically is not available in the provided research articles. However, similar treatments like cinacalcet and etelcalcetide, used for related conditions, have shown that hypocalcemia (low calcium levels) is a common side effect, but they are generally considered safe with careful monitoring. ^{6 7 8 9 10}

Research Team

Calcilytix Medical Director

Principal Investigator

Calcilytix Therapeutics, Inc., a BridgeBio company

Eligibility Criteria

This trial is for people with a genetic variant causing hypoparathyroidism (ADH1), aged 16-18 with closed growth plates, not on certain diuretics or supplements, and meeting specific treatment criteria. Excluded are those recently on PTH treatments, had seizures or thyroid surgery, pregnant/nursing women, low Vitamin D levels, certain viral infections, or severely reduced kidney function.

Inclusion Criteria

I am 16-17 years old and my growth plates are closed.

I have shown symptoms or signs of ADH1.

Participants must meet SoC Optimization criteria as defined in the protocol

Exclusion Criteria

Pregnant or nursing (lactating) women, where pregnancy is confirmed by a positive beta-human chorionic gonadotropin (β-hCG) laboratory test

I have had surgery on my thyroid or parathyroid.

My kidney function is low, with an eGFR below 30 mL/min/1.73 m^2.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 weeks

SoC Optimization

Participants undergo a standard of care optimization phase to confirm eligibility for the main study

Up to 15 weeks

SoC Maintenance

Participants maintain their standard of care dose, adjusted only for safety concerns

4 weeks

Randomized Treatment

Participants are randomized to receive either encaleret or SoC treatment, with doses adjusted based on blood calcium levels

20 weeks

Dose Maintenance

Participants maintain their dose of encaleret or SoC

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-Term Extension (optional)

Participants may opt into continuation of encaleret treatment long-term

Up to 48 months

Treatment Details

Interventions

• Calcium supplements and active Vitamin D
• Encaleret

Trial Overview The study aims to compare the effectiveness and safety of encaleret against standard care in treating ADH1. Participants will receive either encaleret or the usual treatment without knowing which one they're getting to measure differences in health outcomes.

Participant Groups

Group I: Standard of Care (SoC) Experimental Treatment 1 Intervention

Participants will continue receiving calcium supplements and/or active Vitamin D (calcitriol, alfacalcidol, falecalcitriol, etc.)

Group II: Encaleret Experimental Treatment 1 Intervention

Participants will receive encaleret at a dose as needed based on calcium levels.

Who Is Running the Clinical Trial?

Calcilytix Therapeutics, Inc., a BridgeBio company

Lead Sponsor

Trials

3

Recruited

180+

Findings from Research

Cinacalcet effectively lowers serum calcium and parathyroid hormone (PTH) levels in patients with Primary Hyperparathyroidism (PHPT), with a significant normalization of serum calcium observed in 76% of patients across 17 cohort studies and 4 randomized controlled trials (RCTs) involving a total of 940 participants.

The treatment is considered safe, showing no significant difference in overall adverse events compared to placebo, and it is particularly beneficial for patients who cannot undergo parathyroidectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of cinacalcet in primary hyperparathyroidism: a systematic review and meta-analysis of randomized controlled trials and cohort studies. Chandran, M., Bilezikian, JP., Lau, J., et al.[2022]

A 5-month-old boy with idiopathic infantile hypercalcemia (IIH) was successfully treated with pamidronate after other treatments like methylprednisone and furosemide were ineffective, reducing his high calcium levels from 5 mmol/L to 2.95 mmol/L.

The case highlights that pamidronate can be an effective treatment option for IIH, especially when standard therapies do not work, leading to a favorable outcome when the condition is properly diagnosed and treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous pamidronate in the treatment of severe idiopathic infantile hypercalcemia. Skalova, S., Cerna, L., Bayer, M., et al.[2018]

A boy with neonatal severe hyperparathyroidism (NSHPT) due to a mutation in the calcium sensing receptor (CaSR) was successfully treated with the calcimimetic drug cinacalcet, which significantly reduced his parathyroid hormone and calcium levels.

The treatment started at a low dose of 0.5 mg/kg/day and was increased to 5.2 mg/kg/day, demonstrating that type II calcimimetics could be effective for managing NSHPT in newborns, regardless of the specific genetic mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel case of neonatal severe hyperparathyroidism successfully treated with a type II calcimimetic drug. Leunbach, TL., Hansen, AT., Madsen, M., et al.[2021]

In a study of 32 hemodialysis patients with mild-to-moderate secondary hyperparathyroidism (SHPT), early treatment with the calcimimetic cinacalcet significantly reduced parathyroid hormone (PTH) levels and improved calcium and phosphorus control, helping patients meet Kidney Disease Outcomes Quality Initiative (K/DOQI) targets.

After 36 months of treatment, 86.2% of patients achieved target PTH levels, and the average dose of cinacalcet was only 38 mg/day, indicating that early intervention with this medication can effectively manage SHPT with minimal risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early initiation of cinacalcet for the treatment of secondary hyperparathyroidism in hemodialysis patients: a three-year clinical experience. Lucchi, L., Carboni, C., Stipo, L., et al.[2018]

In a study of 174 cancer patients with high serum calcium levels, ibandronate demonstrated a dose-dependent reduction in calcium, with response rates of 44%, 52%, and 67% for doses of 0.6 mg, 1.1 mg, and 2.0 mg, respectively, indicating that higher doses are more effective.

The treatment was generally safe, with a low incidence of adverse events, suggesting that escalating the dose of ibandronate could be beneficial in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcemia of malignancy. Pecherstorfer, M., Herrmann, Z., Body, JJ., et al.[2018]

Pamidronate, a bisphosphonate originally used for neoplastic hypercalcemia, is now being used off-label to treat severe hypercalcemia from various causes.

A case study reported transient electrolyte abnormalities following a single 60 mg intravenous dose of pamidronate, highlighting a potential but infrequent adverse effect of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dyselectrolytemias after single dose of pamidronate administration. Panday, K., Kanth, R.[2018]

WR-2721, a compound used to protect normal tissues during radio- and chemotherapy, causes hypocalcemia by reducing plasma calcium levels and inhibiting parathyroid hormone (PTH) secretion, as shown in studies with rats.

The hypocalcemic effect of WR-2721 is not dependent on phosphate presence or hypomagnesemia, indicating it has unique mechanisms that inhibit renal calcium reabsorption independently of PTH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of parathyroid hormone secretion and parathyroid hormone-independent diminution of tubular calcium reabsorption by WR-2721, a unique hypocalcemic agent. Hirschel-Scholz, S., Caverzasio, J., Bonjour, JP.[2018]

Cinacalcet is a safe and effective treatment for hypercalcemia in patients with primary hyperparathyroidism who cannot have surgery, but it can lead to significant side effects like hypocalcemia.

This case report describes the first known instance of parathyroid apoplexy associated with cinacalcet treatment, highlighting the need for careful monitoring of patients on this medication, especially after reaching higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parathyroid Apoplexy Following Cinacalcet Treatment in Primary Hyperparathyroidism. Di Dalmazi, G., Giuliani, C., Napolitano, G.[2020]

In a 12-month study involving 24 hemodialysis patients with severe secondary hyperparathyroidism, etelcalcetide effectively reduced parathyroid hormone (PTH) levels by over 30% in 83% of participants, demonstrating its efficacy in long-term treatment.

While hypocalcemia was the main side effect observed, it was manageable and not severe enough to stop treatment, suggesting that etelcalcetide is a safe option for patients, particularly those with higher baseline PTH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term efficacy and safety of etelcalcetide in hemodialysis patients with severe secondary hyperparathyroidism]. Massimetti, C., Tondo, M., Feriozzi, S.[2021]

In a phase 1 study involving 11 pediatric hemodialysis patients aged 2 to 18 years, a single dose of etelcalcetide (0.035 mg/kg) was well tolerated, with adverse events consistent with known safety profiles in adults, and no serious adverse events reported.

Etelcalcetide effectively reduced serum intact parathyroid hormone (iPTH) levels, with significant decreases observed within 4 hours post-dose, indicating its potential efficacy in managing secondary hyperparathyroidism in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1, single-dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of etelcalcetide in pediatric patients with secondary hyperparathyroidism receiving hemodialysis. Sohn, W., Salusky, IB., Schmitt, CP., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The efficacy and safety of cinacalcet in primary hyperparathyroidism: a systematic review and meta-analysis of randomized controlled trials and cohort studies. [2022]

2. Iran pubmed.ncbi.nlm.nih.gov

Intravenous pamidronate in the treatment of severe idiopathic infantile hypercalcemia. [2018]

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

A novel case of neonatal severe hyperparathyroidism successfully treated with a type II calcimimetic drug. [2021]

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

Early initiation of cinacalcet for the treatment of secondary hyperparathyroidism in hemodialysis patients: a three-year clinical experience. [2018]

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

Randomized phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcemia of malignancy. [2018]

6. Nepal pubmed.ncbi.nlm.nih.gov

Dyselectrolytemias after single dose of pamidronate administration. [2018]

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

Inhibition of parathyroid hormone secretion and parathyroid hormone-independent diminution of tubular calcium reabsorption by WR-2721, a unique hypocalcemic agent. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Parathyroid Apoplexy Following Cinacalcet Treatment in Primary Hyperparathyroidism. [2020]

9. Italy pubmed.ncbi.nlm.nih.gov

[Long-term efficacy and safety of etelcalcetide in hemodialysis patients with severe secondary hyperparathyroidism]. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Phase 1, single-dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of etelcalcetide in pediatric patients with secondary hyperparathyroidism receiving hemodialysis. [2021]