Clinical trial NCT05778071: Evaluation of the Safety and Efficacy of Eneboparatide (AZP-3601) in Patients With Chronic Hypoparathyroidism
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Hypoparathyroidism
Endocrine System Diseases
Parathyroid Diseases
Keywords: Hypoparathyroidism
Lead sponsor: Amolyt Pharma
Sponsor class: INDUSTRY
First posted: 2023-03-21
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled, double-blind study, with patients randomized in a 2:1 ratio to receive eneboparatide or placebo
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 outcomes:
measure: Efficacy - Primary Endpoint
timeFrame: 24 weeks
Secondary outcomes:
measure: Hypercalciuria
timeFrame: 24 weeks
measure: Change from baseline in the HPT-DD-SE - Physical Domain score
timeFrame: 24 weeks
measure: Change from baseline in the HPT-DD-SE - Cognitive Domain score
timeFrame: 24 weeks
measure: Change from baseline in the HPT-LIQ - Physical Functioning Domain score
timeFrame: 24 weeks
measure: Change from baseline in the SF-36 Physical Functioning subscore
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Harbor UCLA Medical Center Endocrinology
state: California
city: Denver
country: United States
facility: Denver Endocrinology Diabetes and Thyroid Center
state: Colorado
city: Chicago
country: United States
facility: University of Chicago - Medical Center
state: Illinois
city: Evanston
country: United States
facility: North Shore University Health System
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University (IU) Health University Hospital
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Reno
country: United States
facility: Northern Nevada Endocrinology
state: Nevada
city: New York
country: United States
facility: Colombia University Irving Medical Center
state: New York
city: Greenville
country: United States
facility: Physician's East Endocrinology
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia (CHOP)
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadephia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: El Paso
country: United States
facility: Academy of Diabetes, Thyroid and Endocrine
state: Texas
city: Spokane
country: United States
facility: Arthritis Northwest, PLLC
state: Washington
city: Saint John's
country: Canada
facility: Eastern Regional Health Authority Health Sciences Centre
state: Newfoundland and Labrador
city: Oakville
country: Canada
facility: Bone Research and Education Center
state: Ontario
city: Québec
country: Canada
facility: CHU de Quebec Research Centre
city: Aarhus
country: Denmark
facility: Aarhaus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Marseille
country: France
facility: Hopital de la Conception-APHM
city: Nantes
country: France
facility: CHU de Nantes - Hôtel-Dieu
city: Paris
country: France
facility: Hospital Bicetre AP-HP
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus an der TU Dresden
city: Munich
country: Germany
facility: Medicover Neuroendokrinologie MVZ
city: Würzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika
city: Pécs
country: Hungary
facility: Pecsi Tudomanyegyetem
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria de Bologna, Policlinico Sant Orsola Malpighi
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana-Ospedale di Cisanello
city: Roma
country: Italy
facility: Via Alvaro del Portillo, 200, Roma, Italy 00128
city: Chiba
country: Japan
facility: Teikyo University Chiba Medical Center
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Osaka
country: Japan
facility: Osaka City Hospital
city: Osaka
country: Japan
facility: Osaka Metropolital University Hospital
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Tottori
country: Japan
facility: Tottori University Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Eramus MC - University Medical Center
city: Kraków
country: Poland
facility: Medycyny Nuklearnej i Chorob Wewnetrznych
city: Warsaw
country: Poland
facility: Cendrum Zdrowi MDM - EB Group Sp.
city: Łódź
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki. Klinika Endokrynologii Chorob Metabolicznych
city: Lisboa
country: Portugal
facility: Hospital da Luz Lisboa
city: Porto
country: Portugal
facility: Centro Hospital Vila Nova de Faia/Espinho
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Coruña
country: Spain
facility: Complejo Hospitalario Universitario de A Coruna
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: Norwich
country: United Kingdom
facility: Norfolk & Norwich University NHS Foundation Trust, Quadrum Institute
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: Amolyt Pharma
name: Soraya Allas, MD
role: STUDY_DIRECTOR
References: