Informations générales (source: ClinicalTrials.gov)
A Phase 3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Eneboparatide (AZP-3601), a Parathyroid Hormone Receptor Agonist, in Patients With Chronic Hypoparathyroidism (CALYPSO)
Interventional
Phase 3
Alexion Pharmaceuticals, Inc. (Voir sur ClinicalTrials)
juin 2023
juin 2027
02 décembre 2025
This study is investigating the safety and efficacy of eneboparatide (AZP-3601) in
patients with chronic hypoparathyroidism (cHP).
During the first 24 weeks of the trial, participants will be randomized to receive
eneboparatide or placebo. Study treatment is blinded: patients and doctors will not know
which group each patient has been randomized to. All patients will start with a fixed
dose of study treatment (eneboparatide or placebo), administered subcutaneously with a
pre-filled pen. Study treatment will be individually titrated.
After completion of the first 24 weeks, patients will be treated in the open label
extension part of the study for 132 weeks. During this phase, all patients (including
patients that were in the placebo group) will receive eneboparatide.
Etablissements
| Etablissement | Contact | Statut | Actualisé | ||
|---|---|---|---|---|---|
| Etablissement non spécifié, référez vous à la page NCT pour plus d'information Origine et niveau de fiabilité des données | |||||
Critères
Tous
1. Males and Females, 18-80 years of age
2. Patients with cHP for ≥12 months at the time of screening
3. Two paired measurements of showing low parathyroid hormone (PTH) and serum calcium
either below normal or within normal under standard of care
4. Requirement for therapy with calcitriol ≥0.5 mcg per day or alphacalcidol ≥1 mcg per
day, and requirement for supplemental oral calcium treatment ≥1000 mg per day over
and above patient's dietary calcium intake at Day 1 visit
5. Successful completion of the Optimization period based on two consecutive
measurements of albumin-adjusted serum calcium at least 1 week apart within the
range of 7.8 to 9.0 mg/dL and with no more than 25% of change in the daily dose of
any of active vitamin D and oral calcium supplements between the two measurements
6. 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
7. Prior to start of treatment:
- Magnesium level within laboratory normal limits
- 25(OH) vitamin D levels of 30-70 ng/mL (75-175 nmol/L)
8. eGFR ≥30 mL/min/1.73m² during screening
9. Able to perform daily subcutaneous self-injections of study drug (or have a designee
to perform injections) via a pre-filled injection pen
10. Female patients of non-childbearing potential or using an effective method of
contraception throughout the study. Women of childbearing potential should have a
negative pregnancy test.
11. Able and willing to provide written and signed informed consent in accordance with
GCP
Exclusion Criteria:
1. Mental incapacity, unwillingness, or language barriers precluding adequate
understanding or cooperation
2. Clinically significant abnormal values at screening for hematology, clinical
chemistry, coagulation or urinalysis
3. Abnormal arterial pressure at screening, defined as (1) systolic blood pressure <100
mmHg, or (2) systolic blood pressure >150 mmHg, and/or diastolic blood pressure >100
mmHg.
4. Heart rate at rest outside the range of 50-100 beats/minute at screening
5. Clinically significant abnormal standard 12-lead electrocardiogram indicative of
severe cardiac disease
6. Known history of autosomal-dominant hypocalcemia or known pseudohypoparathyroidism
(impaired responsiveness to PTH)
7. Any current disease (other than hypoparathyroidism) that might affect calcium
metabolism, calcium-phosphate homeostasis or PTH levels
8. Patients with increased risk for osteosarcoma
9. Current uncontrolled active disease processes that may adversely affect
gastrointestinal absorption
10. History of cerebrovascular accident within 6 months prior to screening
11. History of active uncontrolled malignancy over the past 2 years at time of screening
12. History of any other cancer other than thyroid cancer (except basal cell skin cancer
or squamous cell skin cancer) who have not been disease-free for a period of at
least 2 years at the time of screening
13. Acute gout <2 months prior to screening
14. Dependent on parenteral calcium infusions to maintain calcium homeostasis
15. Use of medications such as loop and thiazide diuretics, raloxifene hydrochloride,
lithium, methotrexate, cardiac glycosides or systemic corticosteroids within 4 weeks
prior to start of treatment
16. Previous treatment with PTH/parathyroid hormone-related protein-like drugs,
including PTH(1-84) and PTH(1-34) within 3 months of screening
17. Use of other drugs known to influence calcium and bone metabolism within 4 weeks of
screening
18. Use of oral bisphosphonates within 6 months of screening or intravenous
bisphosphonate within 12 months of screening
19. Use of denosumab within 18 months of screening
20. Seizure disorder/epilepsy with history of a seizure within 6 months of screening
21. History of symptomatic urinary tract calculi within 3 months of screening
22. Irradiation to the skeleton within 2 years of screening
23. Pregnant or breastfeeding female patients
24. Participation in any other interventional study in which the patient received an
investigational drug or device within 2 months or within 5 times the half-life of
the investigational drug (whichever comes first) prior to screening
25. Any disease or condition that, in the opinion of the investigator, may require
treatment or make the subject unlikely to fully complete the trial, or any condition
that presents undue risk from the study treatment or procedures, including treated
malignancies that are likely to recur within the approximate duration of the trial
26. Any other reason that in the opinion of the investigator would prevent the subject
from completing participation or following the trial schedule
27. Known allergy or sensitivity to PTH or any of the excipients