A study to test the effects and safety of palopegteriparatide in adolescents with long-term hypoparathyroidism

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ascendis Pharma Bone Diseases A/S

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

22 Apr 2026 → ongoing

Decision date (initial)

2026-03-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic, Efficacy

To evaluate the efficacy of palopegteriparatide in adolescents with chronic hypoparathyroidism

Conditions and MedDRA coding

Chronic hypoparathyroidism

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002955-PIP01-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Males and females, 12 to less than 18 years of age at the time of screening (defined as the date of signing informed consent).
2. Participants with postsurgical chronic hypoparathyroidism, or auto-immune, genetic, or idiopathic hypoparathyroidism for at least 26 weeks. Diagnosis of hypoparathyroidism is established based on historic hypocalcemia in the setting of inappropriately low serum PTH levels (Hypocalcemia is defined as a value below the reference range for normal at the performing laboratory. Inappropriately low serum PTH levels are defined as at or below the median value of the reference range for normal at the performing laboratory while the concomitant serum calcium is low. If specific lab results at the time of original diagnosis are not available, as historical diagnosis affirming these two components is adequate for inclusion).
3. Prior to randomization, achieve normal levels of serum 25(OH) vitamin D and magnesium.
4. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 prior to randomization utilizing the 2009 Schwartz equation: eGFR (mL/min/1.73m^2)= 36.5*((Height (cm))/(Serum Creatinine (µmol/L)))
5. Body mass index (BMI) Z-score greater than -2 SDS and below + 3 SDS at Screening.
6. Written, signed informed consent provided by parent(s) or legally acceptable representative(s) of the participant, and by the participant if in accordance to local health authority/ethics requirements. Assent from participant obtained in accordance with applicable regulatory requirements.
7. Written, signed informed consent provided by parent(s) or legally acceptable representative(s) of the participant, and by the participant if in accordance to local health authority/ethics requirements. Assent from participant obtained in accordance with applicable regulatory requirements.

Exclusion criteria 17

1. Impaired responsiveness to PTH which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia.
2. Any disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than hypoparathyroidism, such as active hyperthyroidism; Paget disease of bone; severe hypomagnesemia; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1C >9%, documented HbA1C result drawn within 12 weeks prior to Screening is acceptable); severe and chronic liver, or renal disease; Cushing syndrome; multiple myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy (other than low-risk well differentiated thyroid cancer or non-melanoma skin cancer); active hyperparathyroidism; parathyroid carcinoma within 5 years prior to Screening; acromegaly; or multiple endocrine neoplasia types 1 and 2.
3. 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). Short course use of steroids (≤2 weeks/year) equivalent to prednisone ≤60 mg/day is permitted.
4. Use of thiazide diuretic within 4 weeks prior to the 24-hour urine collection scheduled to occur within 1 week prior to Visit 1.
5. Use of PTH-like drugs (whether commercially available or through participation in an investigational trial), including PTH(1-84), PTH(1-34), or other N-terminal fragments or analogs of PTH or PTH-related protein, within 4 weeks prior to Screening.
6. Use of other drugs known to influence calcium and bone metabolism, such as calcitonin, fluoride tablets (>0.5 mg/day), strontium, or cinacalcet hydrochloride, within 12 weeks prior to Screening.
7. Use of osteoporosis therapies known to influence calcium and bone metabolism, i.e., bisphosphonate (oral or intravenous [IV]), denosumab, raloxifene, or romosozumab therapies within 2 years prior to Screening.
8. Non-hypocalcemic seizure disorder with occurrence of a seizure within 26 weeks prior to Screening.Note: History of seizures that occur in the setting of hypocalcemia is not exclusionary.
9. Increased risk for osteosarcoma, such as those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, hereditary disorders predisposing to osteosarcoma, or with a prior history of substantial external beam or implant radiation therapy involving the skeleton.
10. Female participants who are pregnant, intend to become pregnant, or are lactating. Note: Acceptable, effective contraception is required for sexually active women of childbearing potential during the trial and for 2 weeks after the last dose of investigational product.
11. Diagnosed drug or alcohol dependence within 3 years prior to Screening.
12. Symptomatic or severe cardiac disease within 26 weeks prior to Screening including but not limited to congestive heart failure, symptomatic or severe valvular disease, myocardial infarction, severe or uncontrolled arrhythmias, bradycardia, symptomatic hypotension, abnormal systolic BP, or poorly controlled hypertension based on age and sex-specific reference ranges.
13. Cerebrovascular accident within 5 years prior to Screening.
14. Within 26 weeks prior to Screening: acute colic due to nephrolithiasis or acute gout. Note: Participants with asymptomatic renal stones are permitted.
15. Participation in any other interventional trial in which receipt of investigational product or device occurred within 8 weeks (or within 5.5 times the half-life of the investigational product) (whichever comes first) prior to Screening.
16. Known allergy or sensitivity to PTH or any of the excipients [metacresol, mannitol, succinic acid, NaOH/(HCl)] of the investigational product.
17. Any other reason that in the opinion of the investigator would prevent the participant from completing participation or following the trial schedule.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. At Week 26, proportion of participants with: Albumin-adjusted serum calcium within the normal range measured within 4 weeks prior to and on the Week 26 visit; and
2. Independence from active vitamin D and
3. Independence from therapeutic doses of calcium. Calcium ≤600 mg/day (in the form of tablets, powder, liquid suspension, or transdermal patch) is considered as “supplemental” to meet recommended daily intake for general health, as opposed to a “therapeutic” dose to treat hypoparathyroidism

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ascendis Pharma Bone Diseases A/S

Sponsor organisation

Ascendis Pharma Bone Diseases A/S

Address

Tuborg Boulevard 12

City

Hellerup

Postcode

2900

Country

Denmark

Scientific contact point

Organisation

Ascendis Pharma Bone Diseases A/S

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

Ascendis Pharma Bone Diseases A/S

Contact name

Clinical Trial Information Desk

Third parties 9

Locations

4 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications