Eneboparatide for Hypoparathyroidism

(CALYPSO Trial)

Not currently recruiting at 63 trial locations

Overseen By Amolyt Contact CTA

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion Pharmaceuticals, Inc.

Must be taking: Calcitriol, Alphacalcidol, Calcium supplements

Must not be taking: Diuretics, Corticosteroids, Bisphosphonates, others

Disqualifiers: Cancer, Seizures, Osteosarcoma risk, 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: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called eneboparatide for individuals with chronic hypoparathyroidism, a condition where insufficient parathyroid hormone leads to low calcium levels. The study aims to determine if eneboparatide is safe and effective compared to a placebo (a look-alike injection with no active drug). After the initial 24 weeks, all participants will receive eneboparatide for over two years to assess its long-term effects. Adults with chronic hypoparathyroidism for at least a year who currently take supplements like calcitriol and calcium may be suitable for this study. Participants should be comfortable with or have assistance for daily self-injections. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as loop and thiazide diuretics, lithium, and systemic corticosteroids, at least 4 weeks before starting the treatment. If you are on medications that affect calcium and bone metabolism, you may also need to stop those before joining the trial.

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

Research has shown that eneboparatide is generally safe for people. One study found that after 24 weeks of using eneboparatide, adults with long-term low calcium levels due to chronic hypoparathyroidism had their calcium levels return to normal, which is important for good health. Patients also generally responded well to the treatment during this period. Another study found that after three months, most patients could stop their usual treatment while keeping their calcium levels stable. These results suggest that eneboparatide could be a safe option for managing this condition. ^{1 2 3 4 5}

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

Eneboparatide is unique because it offers a novel approach to treating hypoparathyroidism through a once-daily subcutaneous injection. Unlike standard treatments such as calcium and vitamin D supplements, eneboparatide directly addresses the deficiency by mimicking the action of parathyroid hormone, potentially providing more precise control over calcium levels. Researchers are excited because this could lead to fewer complications and more stable calcium levels, significantly improving the quality of life for patients with this condition.

What evidence suggests that eneboparatide could be an effective treatment for chronic hypoparathyroidism?

Research has shown that eneboparatide, which participants in this trial may receive, effectively treats long-term low parathyroid hormone levels, known as chronic hypoparathyroidism. In one study, over 88% of patients stopped using their regular treatments after just three months. Another study found that eneboparatide restored normal blood calcium levels after 24 weeks. These findings suggest that eneboparatide can help maintain healthy calcium levels and reduce the need for other medications. ^{1 2 3 4 5}

Who Is on the Research Team?

Soraya Allas, MD

Principal Investigator

Amolyt Pharma

Are You a Good Fit for This Trial?

Adults aged 18-80 with chronic hypoparathyroidism, requiring daily treatments for calcium and vitamin D intake. Participants must be able to self-inject medication or have someone who can do it for them, not be pregnant or breastfeeding, and have stable health without conditions that affect calcium metabolism. They should also not have had recent seizures or certain cancer treatments.

Inclusion Criteria

Prior to start of treatment:

Thyroid-stimulating hormone (TSH) within the lower limit of normal and 1.5-fold of the upper limit of normal at screening; if on suppressive therapy for a history of thyroid cancer, TSH level must be ≥0.2 mIU/mL and thyroid medication should be stable for at least 6 weeks prior to treatment

Magnesium level within laboratory normal limits

Exclusion Criteria

I do not have any uncontrolled illnesses that could affect my stomach or intestines.

I have not taken oral bisphosphonates in the last 6 months or IV bisphosphonates in the last year.

Clinically significant abnormal values at screening for hematology, clinical chemistry, coagulation or urinalysis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive eneboparatide or placebo for 24 weeks, with treatment administered subcutaneously and individually titrated

24 weeks

Open-label extension

All participants receive eneboparatide for 132 weeks, including those initially in the placebo group

132 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Eneboparatide
• Placebo

Trial Overview The trial is testing eneboparatide (AZP-3601) against a placebo in patients with chronic hypoparathyroidism over a period of 52 weeks. Initially, participants won't know if they're receiving the actual drug or a placebo. After 24 weeks, all will receive eneboparatide in an open label extension phase.

How Is the Trial Designed?

Group I: eneboparatide Experimental Treatment 1 Intervention

Starting dose of 20 mcg; Administered once daily by subcutaneous injection

Group II: Placebo Placebo Group 1 Intervention

Administered once daily by subcutaneous injection

Who Is Running the Clinical Trial?

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Amolyt Pharma

Industry Sponsor

Trials

2

Recruited

300+

Published Research Related to This Trial

PTH therapy likely provides a small improvement in physical health-related quality of life for patients with chronic hypoparathyroidism compared to conventional therapy, based on a systematic review of 7 randomized trials involving 386 patients.

PTH therapy significantly increases the likelihood of patients achieving a 50% or greater reduction in the dose of active vitamin D and calcium, although it may also raise the risk of hypercalcemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parathyroid Hormone Therapy for Managing Chronic Hypoparathyroidism: A Systematic Review and Meta-Analysis. Yao, L., Li, J., Li, M., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38449442/

An Open-label Phase 2 Study of Eneboparatide, a Novel ... Results: After 3 months, ≥ 88% of patients achieved independence from conventional therapy while mean ADsCa was maintained within target range ( ...

2. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/Eneboparatide-met-primary-endpoint-of-normalizing-serum-calcium-in-adults-with-hypoparathyroidism-at-24-weeks-in-CALYPSO-Phase-III-trial.html

Eneboparatide met primary endpoint of normalizing serum ... The primary endpoint is a composite of normalization of albumin-adjusted serum calcium levels and independence from active vitamin D and oral calcium therapy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05778071

Study Details | NCT05778071 | Evaluation of the Safety ... This study is investigating the safety and efficacy of eneboparatide (AZP-3601) in patients with chronic hypoparathyroidism (cHP).

4. touchendocrinology.com touchendocrinology.com/insight/eneboparatide-meets-primary-endpoint-in-adults-with-hypoparathyroidism-calypso-topline-phase-iii-results/

Eneboparatide meets primary endpoint in adults with ... After 24 weeks, the primary endpoint was achieved, with eneboparatide found to significantly normalize serum calcium levels in adults with chronic HypoPT, ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40423237/

Phase 1 clinical trial of eneboparatide, a novel PTH ... These data suggest that eneboparatide may provide sustained control of serum calcium in patients with hypoparathyroidism with once daily dosing.