Evaluation of the Safety and Efficacy of Eneboparatide (AZP-3601) in Patients With Chronic Hypoparathyroidism (CALYPSO)

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)

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 28 weeks. During this phase, all patients (including patients that were in the placebo group) will receive eneboparatide.

Study Overview

• Status: Active, not recruiting
• Conditions: Endocrine System Diseases; Parathyroid Diseases; Chronic Hypoparathyroidism
• Intervention / Treatment: Combination product: eneboparatide; Combination product: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 165
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4G2
    • CHU de Quebec Research Centre
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Eastern Regional Health Authority Health Sciences Centre
  • Ontario
    • Oakville, Ontario, Canada, L6M 1M1
      • Bone Research and Education Center
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhaus University Hospital
  • Copenhagen, Denmark
    • Rigshospitalet
• France
  • Marseille, France, 13385
    • Hopital de la Conception-APHM
  • Nantes, France, 44093
    • CHU de Nantes - Hôtel-Dieu
  • Paris, France, 94275
    • Hospital Bicetre AP-HP
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus an der TU Dresden
  • Munich, Germany, 81667
    • Medicover Neuroendokrinologie MVZ
  • Würzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika
  • Pécs, Hungary, 7624
    • Pecsi Tudomanyegyetem
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria de Bologna, Policlinico Sant Orsola Malpighi
  • Firenze, Italy, 50134
    • Azienda Ospedaliera Universitaria Careggi
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
  • Pisa, Italy, 56124
    • Azienda Ospedaliera Universitaria Pisana-Ospedale di Cisanello
  • Roma, Italy, 00128
    • Via Alvaro del Portillo, 200, Roma, Italy 00128
• Netherlands
  • Leiden, Netherlands, 2333
    • Leiden University Medical Center
  • Rotterdam, Netherlands, 3015 GD
    • Eramus MC - University Medical Center
• Poland
  • Kraków, Poland, 30-688
    • Medycyny Nuklearnej i Chorob Wewnetrznych
  • Warsaw, Poland, 00189
    • Cendrum Zdrowi MDM - EB Group Sp.
  • Łódź, Poland, 93-338
    • Instytut Centrum Zdrowia Matki Polki. Klinika Endokrynologii Chorob Metabolicznych
• Portugal
  • Lisboa, Portugal, 1500-650
    • Hospital da Luz Lisboa
  • Porto, Portugal, 4434-502
    • Centro Hospital Vila Nova de Faia/Espinho
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Coruña, Spain, 15006
    • Complejo Hospitalario Universitario de A Coruna
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • University Hospitals of Leicester Nhs Trust
  • Norwich, United Kingdom, NR4 7UQ
    • Norfolk & Norwich University NHS Foundation Trust, Quadrum Institute
  • Oxford, United Kingdom, OX3 7LE
    • Churchill Hospital
• United States
  • California
    • Torrance, California, United States, 90502
      • Harbor UCLA Medical Center Endocrinology
  • Colorado
    • Denver, Colorado, United States, 80113
      • Denver Endocrinology Diabetes and Thyroid Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago - Medical Center
    • Evanston, Illinois, United States, 60201
      • North Shore University Health System
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University (IU) Health University Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nevada
    • Reno, Nevada, United States, 89511
      • Northern Nevada Endocrinology
  • New York
    • New York, New York, United States, 10032
      • Colombia University Irving Medical Center
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Physician's East Endocrinology
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadephia
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia (CHOP)
  • Texas
    • El Paso, Texas, United States, 79935
      • Academy of Diabetes, Thyroid and Endocrine
  • Washington
    • Spokane, Washington, United States, 99204
      • Arthritis Northwest, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eneboparatide; Starting dose of 20 mcg; Administered once daily by subcutaneous injection	Combination product: eneboparatide; Supplied as a solution (concentration of 250 mcg/mL or 500 mcg/mL) in single-patient-use prefilled pens; Other Names: AZP-3601
Placebo Comparator: Placebo; Administered once daily by subcutaneous injection	Combination product: Placebo; Placebo is supplied as a solution (containing the excipient solution for eneboparatide) in single-patient-use prefilled pens

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy - Primary Endpoint	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).	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypercalciuria	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)	24 weeks
Change from baseline in the HPT-DD-SE - Physical Domain score	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	24 weeks
Change from baseline in the HPT-DD-SE - Cognitive Domain score	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	24 weeks
Change from baseline in the HPT-LIQ - Physical Functioning Domain score	Change from baseline in the HPT-LIQ Physical Functioning domain score, in the eneboparatide treatment group vs. placebo	24 weeks
Change from baseline in the SF-36 Physical Functioning subscore	Change from baseline in the SF-36 Physical Functioning subscore in the eneboparatide treatment group vs. placebo	24 weeks

Collaborators and Investigators

• Sponsor: Amolyt Pharma
• Investigators: Study Director: Soraya Allas, MD, Amolyt Pharma

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: March 9, 2023
• First Submitted That Met QC Criteria: March 9, 2023
• First Posted (Actual): March 21, 2023

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Hypoparathyroidism
• Additional Relevant MeSH Terms: Endocrine System Diseases; Hypoparathyroidism; Parathyroid Diseases
• Other Study ID Numbers: AZP-3601-CLI-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No