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

Endocrine System Diseases Clinical Trial

— CALYPSO  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05778071
• Other study ID #: AZP-3601-CLI-002
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 7, 2023
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: Amolyt Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 165
• Est. completion date: June 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hypoparathyroidism
• Endocrine System Diseases
• Hypoparathyroidism
• Parathyroid Diseases

Intervention

Combination Product:
• 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

Locations

Country	Name	City	State
Canada	Bone Research and Education Center	Oakville	Ontario
Canada	CHU de Quebec Research Centre	Québec
Canada	Eastern Regional Health Authority Health Sciences Centre	Saint John's	Newfoundland and Labrador
Denmark	Aarhaus University Hospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
France	Hopital de la Conception-APHM	Marseille
France	CHU de Nantes - Hôtel-Dieu	Nantes
France	Hospital Bicetre AP-HP	Paris
Germany	Universitatsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	Medicover Neuroendokrinologie MVZ	Munich
Germany	Universitaetsklinikum Wuerzburg	Würzburg
Hungary	Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika	Budapest
Hungary	Pecsi Tudomanyegyetem	Pécs
Italy	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
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Eramus MC - University Medical Center	Rotterdam
Poland	Medycyny Nuklearnej i Chorob Wewnetrznych	Kraków
Poland	Instytut Centrum Zdrowia Matki Polki. Klinika Endokrynologii Chorob Metabolicznych	Lódz
Poland	Cendrum Zdrowi MDM - EB Group Sp.	Warsaw
Portugal	Hospital da Luz Lisboa	Lisboa
Portugal	Centro Hospital Vila Nova de Faia/Espinho	Porto
Spain	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
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester
United Kingdom	Norfolk & Norwich University NHS Foundation Trust, Quadrum Institute	Norwich
United Kingdom	Churchill Hospital	Oxford
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Chicago - Medical Center	Chicago	Illinois
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Denver Endocrinology Diabetes and Thyroid Center	Denver	Colorado
United States	Academy of Diabetes, Thyroid and Endocrine	El Paso	Texas
United States	North Shore University Health System	Evanston	Illinois
United States	Physician's East Endocrinology	Greenville	North Carolina
United States	Indiana University (IU) Health University Hospital	Indianapolis	Indiana
United States	Colombia University Irving Medical Center	New York	New York
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	Northern Nevada Endocrinology	Reno	Nevada
United States	Mayo Clinic	Rochester	Minnesota
United States	Arthritis Northwest, PLLC	Spokane	Washington
United States	Harbor UCLA Medical Center Endocrinology	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Amolyt Pharma

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Germany,  Hungary,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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