Evaluation of the Safety and Efficacy of Eneboparatide (AZP-3601) in Patients With Chronic Hypoparathyroidism
- Conditions
- Endocrine System DiseasesParathyroid DiseasesChronic Hypoparathyroidism
- Interventions
- Combination Product: eneboparatideCombination Product: Placebo
- Registration Number
- NCT05778071
- Lead Sponsor
- Amolyt Pharma
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 165
-
Males and Females, 18-80 years of age
-
Patients with cHP for ≥12 months at the time of screening
-
Two paired measurements of showing low parathyroid hormone (PTH) and serum calcium either below normal or within normal under standard of care
-
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
-
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
-
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
-
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)
-
eGFR ≥30 mL/min/1.73m² during screening
-
Able to perform daily subcutaneous self-injections of study drug (or have a designee to perform injections) via a pre-filled injection pen
-
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.
-
Able and willing to provide written and signed informed consent in accordance with GCP
- Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation
- Clinically significant abnormal values at screening for hematology, clinical chemistry, coagulation or urinalysis
- 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.
- Heart rate at rest outside the range of 50-100 beats/minute at screening
- Clinically significant abnormal standard 12-lead electrocardiogram indicative of severe cardiac disease
- Known history of autosomal-dominant hypocalcemia or known pseudohypoparathyroidism (impaired responsiveness to PTH)
- Any current disease (other than hypoparathyroidism) that might affect calcium metabolism, calcium-phosphate homeostasis or PTH levels
- Patients with increased risk for osteosarcoma
- Current uncontrolled active disease processes that may adversely affect gastrointestinal absorption
- History of cerebrovascular accident within 6 months prior to screening
- History of active uncontrolled malignancy over the past 2 years at time of screening
- 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
- Acute gout <2 months prior to screening
- Dependent on parenteral calcium infusions to maintain calcium homeostasis
- 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
- Previous treatment with PTH/parathyroid hormone-related protein-like drugs, including PTH(1-84) and PTH(1-34) within 3 months of screening
- Use of other drugs known to influence calcium and bone metabolism within 4 weeks of screening
- Use of oral bisphosphonates within 6 months of screening or intravenous bisphosphonate within 12 months of screening
- Use of denosumab within 18 months of screening
- Seizure disorder/epilepsy with history of a seizure within 6 months of screening
- History of symptomatic urinary tract calculi within 3 months of screening
- Irradiation to the skeleton within 2 years of screening
- Pregnant or breastfeeding female patients
- 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
- 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
- Any other reason that in the opinion of the investigator would prevent the subject from completing participation or following the trial schedule
- Known allergy or sensitivity to PTH or any of the excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description eneboparatide eneboparatide Starting dose of 20 mcg; Administered once daily by subcutaneous injection Placebo Placebo Administered once daily by subcutaneous injection
- Primary Outcome Measures
Name Time Method 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).
- Secondary Outcome Measures
Name Time Method Hypercalciuria 24 weeks Proportion of patients who had hypercalciuria at baseline and normalize 24-hour urinary calcium excretion level (i.e., achieve \<250 mg/24 hours for females or \<300 mg/24 hours for males)
Change from baseline in the SF-36 Physical Functioning subscore 24 weeks Change from baseline in the SF-36 Physical Functioning subscore in the eneboparatide treatment group vs. placebo
Change from baseline in the HPT-DD-SE - Cognitive Domain score 24 weeks Change from baseline in patient's symptoms, as assessed by the average weekly HPT-DD-SE cognitive domain score in the eneboparatide treatment group vs. placebo
Change from baseline in the HPT-DD-SE - Physical Domain score 24 weeks Change from baseline in patient's symptoms, as assessed by the average weekly HPT-DD-SE physical domain score in the eneboparatide treatment group vs. placebo
Change from baseline in the HPT-LIQ - Physical Functioning Domain score 24 weeks Change from baseline in the HPT-LIQ Physical Functioning domain score, in the eneboparatide treatment group vs. placebo
Trial Locations
- Locations (54)
Osaka City Hospital
🇯🇵Osaka, Japan
Northern Nevada Endocrinology
🇺🇸Reno, Nevada, United States
Bone Research and Education Center
🇨🇦Oakville, Ontario, Canada
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
🇮🇹Firenze, Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria Pisana-Ospedale di Cisanello
🇮🇹Pisa, Italy
Via Alvaro del Portillo, 200, Roma, Italy 00128
🇮🇹Roma, Italy
Osaka Metropolital University Hospital
🇯🇵Osaka, Japan
Tottori University Hospital
🇯🇵Tottori, Japan
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Eramus MC - University Medical Center
🇳🇱Rotterdam, Netherlands
Medycyny Nuklearnej i Chorob Wewnetrznych
🇵🇱Kraków, Poland
Cendrum Zdrowi MDM - EB Group Sp.
🇵🇱Warsaw, Poland
Instytut Centrum Zdrowia Matki Polki. Klinika Endokrynologii Chorob Metabolicznych
🇵🇱Łódź, Poland
Hospital da Luz Lisboa
🇵🇹Lisboa, Portugal
Centro Hospital Vila Nova de Faia/Espinho
🇵🇹Porto, Portugal
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Complejo Hospitalario Universitario de A Coruna
🇪🇸Coruña, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Rigshospitalet
🇩🇰Copenhagen, Denmark
Hopital de la Conception-APHM
🇫🇷Marseille, France
Hospital Bicetre AP-HP
🇫🇷Paris, France
Universitatsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪Dresden, Germany
Medicover Neuroendokrinologie MVZ
🇩🇪Munich, Germany
Tokushima University Hospital
🇯🇵Tokushima, Japan
Harbor UCLA Medical Center Endocrinology
🇺🇸Torrance, California, United States
Denver Endocrinology Diabetes and Thyroid Center
🇺🇸Denver, Colorado, United States
University of Chicago - Medical Center
🇺🇸Chicago, Illinois, United States
North Shore University Health System
🇺🇸Evanston, Illinois, United States
Indiana University (IU) Health University Hospital
🇺🇸Indianapolis, Indiana, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Colombia University Irving Medical Center
🇺🇸New York, New York, United States
Physician's East Endocrinology
🇺🇸Greenville, North Carolina, United States
Arthritis Northwest, PLLC
🇺🇸Spokane, Washington, United States
CHU de Quebec Research Centre
🇨🇦Québec, Canada
CHU de Nantes - Hôtel-Dieu
🇫🇷Nantes, France
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
The Children's Hospital of Philadelphia (CHOP)
🇺🇸Philadelphia, Pennsylvania, United States
The Children's Hospital of Philadephia
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Academy of Diabetes, Thyroid and Endocrine
🇺🇸El Paso, Texas, United States
Eastern Regional Health Authority Health Sciences Centre
🇨🇦Saint John's, Newfoundland and Labrador, Canada
Aarhaus University Hospital
🇩🇰Aarhus, Denmark
Teikyo University Chiba Medical Center
🇯🇵Chiba, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Japan
University Hospitals of Leicester NHS Trust
🇬🇧Leicester, United Kingdom
Norfolk & Norwich University NHS Foundation Trust, Quadrum Institute
🇬🇧Norwich, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom