A Phase 3 Randomized Clinical Trial to Investigate the Safety and Efficacy of Palopegteriparatide at Doses Greater Than 30 μg/Day in Adult Participants With Hypoparathyroidism

NCT07081997 | Recruiting Phase 3 FDA Drug

• 1 other identifier: ASND0052
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

This trial has a duration of 78 weeks and will include adult participants already on treatment with palopegteriparatide at doses at or greater than 30 mcg/day. All participants will receive subcutaneous palopegteriparatide during the trial and will be individually and progressively titrated to an optimal dose at pre-specified dose levels. The primary purpose of the trial is to provide additional evidence of treatment effect and safety of palopegteriparatide at doses greater than 30 mcg/day in adults with hypoparathyroidism. The trial will be conducted in the US.

Conditions

Endocrine System Diseases; Hypoparathyroidism; Parathyroid Diseases

Keywords

Hypoparathyroidism; Parathyroid Hormone; TransCon PTH; PTH(1-34); Prodrug; Sustained Release; Parathyroid Hormone Replacement Therapy; Palopegteriparatide

Outcome Measures

Primary Outcomes (1)

• Efficacy - Primary endpoint

  The proportion of participants with: Albumin-adjusted serum calcium (sCa) measured within 4 weeks prior to and on the Week 26 visit within the normal range (8.3-10.6 mg/dL); and independence from active vitamin D; and independence from therapeutic doses of calcium; and no increase in prescribed investigational product within 4 weeks prior to Week 26 visit.

  26 weeks

Study Arms (2)

Palopegteriparatide Experimental Arm

EXPERIMENTAL

Palopegteriparatide at doses at or greater than 30 mcg delivered once daily by subcutaneous injection and titrated to an optimal dose by a novel titration algorithm.

Combination Product: Palopegteriparatide Experimental Arm

Palopegteriparatide Control Arm

ACTIVE COMPARATOR

Palopegteriparatide at doses at or greater than 30 mcg delivered once daily by subcutaneous injection and titrated to an optimal dose by a previously evaluated titrated algorithm

Combination Product: Palopegteriparatide Control Arm

Interventions

Palopegteriparatide Experimental Arm COMBINATION_PRODUCT

Palopegteriparatide is supplied as a solution with a concentration of 0.3 mg/mL in a single-patient-use prefilled pen intended for subcutaneous injection.

Also known as: Yorvipath

Palopegteriparatide Experimental Arm

Palopegteriparatide Control Arm COMBINATION_PRODUCT

Palopegteriparatide is supplied as a solution with a concentration of 0.3 mg/mL in a single-patient-use prefilled pen intended for subcutaneous injection.

Also known as: Yorvipath

Palopegteriparatide Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, ≥18 years of age at the time of providing informed consent
• Participants with postsurgical chronic hypoparathyroidism (HP), or auto-immune, genetic, or idiopathic HP, for at least 26 weeks
• Receiving doses of palopegteriparatide at or above 30 µg/day
• For individuals receiving 30 µg/day: evidence that dose is insufficient to keep serum calcium in the normal range, defined as:
• Documented hypocalcemia within 12 weeks prior to Screening; and/or Standing dose of calcitriol ≥0.25 μg/day, and / or (elemental) calcium ≥1500 mg/day (e.g., calcium citrate, calcium carbonate etc.) for at least 4 weeks prior to Screening
• For individuals receiving 33 µg/day or greater: no requirement for documented hypocalcemia or minimum doses of calcitriol or elemental calcium
• Confirmation of laboratory parameters (Central and Local) within 2 weeks of screening visit and prior to randomization:
• (OH) vitamin D levels of 20 - 80 ng/mL (49 - 200 nmol/L) and Magnesium level in the normal range, or just below the normal range i.e.: ≥1.3 mg/dL (≥0.53 mmol/L) and Albumin-adjusted or ionized sCa level in the normal range or just below the normal range
• Albumin-adjusted sCa 7.8 - 10.6 mg/dL (or 1.95 - 2.64 mmol/L)
• Ionized sCa 4.40 - 5.29 mg/dL (1.10 - 1.32 mmol/L)
• \. BMI 17- 40 kg/m2 at Screening
• \. If ≤25 years of age, radiological evidence of epiphyseal closure based on locally interpreted X-ray of non-dominant wrist and hand
• \. eGFR ≥30 mL/min/1.73 m2 during Screening using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula

You may not qualify if:

• Impaired responsiveness to PTH (pseudohypoparathyroidism), which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia
• Any disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than HP
• Use of loop diuretics, phosphate binders (other than calcium supplements), digoxin, lithium, methotrexate, biotin \>30 µg/day, or systemic corticosteroids (other than as replacement therapy)
• Use of thiazide diuretic within 4 weeks prior to the 24-hour urine collection scheduled to occur within 1 week prior to Visit 1
• Use of PTH-like drugs other than palopegteriparatide (whether commercially available or through participation in an investigational trial), including PTH(1-34), or other N-terminal fragments, analogs of PTH or PTH-related protein, or PTH1R biased agonists within 4 weeks prior to Screening
• Use of drugs known to influence calcium and bone metabolism within 12 weeks prior to Screening
• Non-hypocalcemic seizure disorder with occurrence of a seizure within 26 weeks prior to Screening.
• Increased risk for osteosarcoma
• Women who are pregnant, intend to become pregnant, or are lactating
• Male who has a female partner who intends to become pregnant or is of childbearing potential and is unwilling to use adequate contraceptive methods during the trial
• Diagnosed drug or alcohol dependence within 3 years prior to Screening
• Chronic or severe cardiac disease within 26 weeks prior to Screening
• Cerebrovascular accident within 5 years prior to Screening.
• Within 26 weeks prior to Screening: acute colic due to nephrolithiasis, or acute gout
• Participation in any other interventional trial in which receipt of investigational drug or device other than palopegteriparatide occurred within 8 weeks (or within 5.5 times the half-life of the investigational drug) (whichever comes first) prior to Screening.

Sponsors & Collaborators

• Ascendis Pharma Bone Diseases A/S: lead

Study Sites (3)

Ascendis Pharma Investigational Site

Reno, Nevada, 89511, United States

RECRUITING

Ascendis Pharma Investigational Site

New York, New York, 10032, United States

RECRUITING

Ascendis Pharma Investigational Site

Spokane Valley, Washington, 99216, United States

RECRUITING

MeSH Terms

Conditions

Hypoparathyroidism; Endocrine System Diseases; Parathyroid Diseases

Study Officials

• Medical Director, MD

  Ascendis Pharma A/S

  STUDY DIRECTOR

Central Study Contacts

Ascendis Registry Inquiries

CONTACT

+4561161658; asnd_registryinquiries@ascendispharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label randomized multi-center

Study Record Dates

• First Submitted: July 22, 2025
• First Posted: July 24, 2025
• Study Start: April 16, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)