Chronic HypoparathyroidismEndocrine System DiseasesParathyroid Diseases
Investigational drug(s) / intervention(s)
eneboparatidePlacebo
eneboparatide: Supplied as a solution (concentration of 250 mcg/mL or 500 mcg/mL) in single-patient-use prefilled pens
Placebo: Placebo is supplied as a solution (containing the excipient solution for eneboparatide) in single-patient-use prefilled pens
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
Inclusion Criteria:
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
Primary outcome measure(s)
Efficacy - Primary Endpoint — 24 weeks After 24 weeks of treatment, the proportion of patients in the eneboparatide treatment group vs. placebo:
* Achieving complete independence from active vitamin D;
* Achieving independence from therapeutic doses of oral calcium (i.e. taking oral elemental calcium supplements ≤600 mg/day); and
* With albumin-adjusted serum calcium within the normal range (8.3 to 10.6 mg/dL).
Trial sites (54)
Facility
City
Region
Status
Harbor UCLA Medical Center Endocrinology
Torrance
California
Denver Endocrinology Diabetes and Thyroid Center
Denver
Colorado
University of Chicago - Medical Center
Chicago
Illinois
North Shore University Health System
Evanston
Illinois
Indiana University (IU) Health University Hospital
Indianapolis
Indiana
Massachusetts General Hospital
Boston
Massachusetts
Mayo Clinic
Rochester
Minnesota
Northern Nevada Endocrinology
Reno
Nevada
Colombia University Irving Medical Center
New York
New York
Physician's East Endocrinology
Greenville
North Carolina
The Ohio State University Wexner Medical Center
Columbus
Ohio
The Children's Hospital of Philadelphia (CHOP)
Philadelphia
Pennsylvania
The Children's Hospital of Philadephia
Philadelphia
Pennsylvania
Thomas Jefferson University
Philadelphia
Pennsylvania
Academy of Diabetes, Thyroid and Endocrine
El Paso
Texas
Arthritis Northwest, PLLC
Spokane
Washington
Eastern Regional Health Authority Health Sciences Centre
St. John's
Newfoundland and Labrador
Bone Research and Education Center
Oakville
Ontario
CHU de Quebec Research Centre
Québec
Canada
Aarhaus University Hospital
Aarhus
Denmark
Rigshospitalet
Copenhagen
Denmark
Hopital de la Conception-APHM
Marseille
France
CHU de Nantes - Hôtel-Dieu
Nantes
France
Hospital Bicetre AP-HP
Paris
France
Universitatsklinikum Carl Gustav Carus an der TU Dresden
Dresden
Germany
Medicover Neuroendokrinologie MVZ
Munich
Germany
Universitaetsklinikum Wuerzburg
Würzburg
Germany
Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika
Budapest
Hungary
Pecsi Tudomanyegyetem
Pécs
Hungary
Azienda Ospedaliero Universitaria de Bologna, Policlinico Sant Orsola Malpighi
Bologna
Italy
Azienda Ospedaliera Universitaria Careggi
Florence
Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
Milan
Italy
Azienda Ospedaliera Universitaria Pisana-Ospedale di Cisanello
Pisa
Italy
Via Alvaro del Portillo, 200, Roma, Italy 00128
Roma
Italy
Teikyo University Chiba Medical Center
Chiba
Japan
Kanazawa University Hospital
Kanazawa
Japan
Osaka City Hospital
Osaka
Japan
Osaka Metropolital University Hospital
Osaka
Japan
Tokushima University Hospital
Tokushima
Japan
Tottori University Hospital
Tottori
Japan
+ 14 more sites — see the full list on the official registry below.
More Alexion Pharmaceuticals, Inc. trials in the UK
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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