Chronic HypoparathyroidismPhase 3CALYPSONCT05778071
Evaluation of the Safety and Efficacy of Eneboparatide (AZP-3601) in Patients With Chronic Hypoparathyroidism
A Phase 3 study testing eneboparatide in people with Chronic Hypoparathyroidism and Endocrine System Diseases, run by Alexion Pharmaceuticals, Inc. at 54 sites in 13 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Hypoparathyroidism, Endocrine System Diseases, Parathyroid Diseases
- What is being tested?
- eneboparatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 165 participants
- Where
- 54 sitesin 13 countries
- Study dates
- 7 Jun 2023to 16 Jun 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
Show all 27Show fewer
- 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
Trial locations and contacts
54 sites in 13 countries.
54 sites in 13 countries
United States16 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Chicago - Medical Center
Chicago, Illinois, 60637
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Denver Endocrinology Diabetes and Thyroid Center
Denver, Colorado, 80113
Academy of Diabetes, Thyroid and Endocrine
El Paso, Texas, 79935
North Shore University Health System
Evanston, Illinois, 60201
Physician's East Endocrinology
Greenville, North Carolina, 27834
Indiana University (IU) Health University Hospital
Indianapolis, Indiana, 46202
Colombia University Irving Medical Center
New York, New York, 10032
The Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
The Children's Hospital of Philadephia
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Northern Nevada Endocrinology
Reno, Nevada, 89511
Mayo Clinic
Rochester, Minnesota, 55905
Arthritis Northwest, PLLC
Spokane, Washington, 99204
Harbor UCLA Medical Center Endocrinology
Torrance, California, 90502
Japan6 sites
Teikyo University Chiba Medical Center
Chiba
Kanazawa University Hospital
Kanazawa
Osaka City Hospital
Osaka
Osaka Metropolital University Hospital
Osaka
Tokushima University Hospital
Tokushima
Tottori University Hospital
Tottori
Italy5 sites
Azienda Ospedaliero Universitaria de Bologna, Policlinico Sant Orsola Malpighi
Bologna, 40138
Azienda Ospedaliera Universitaria Careggi
Florence, 50134
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
Milan, 20122
Azienda Ospedaliera Universitaria Pisana-Ospedale di Cisanello
Pisa, 56124
Via Alvaro del Portillo, 200, Roma, Italy 00128
Roma, 00128
Spain4 sites
Complejo Hospitalario Universitario de A Coruna
A Coruña, 15006
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Clinica Universidad de Navarra
Pamplona, 31008
Hospital Universitario Virgen del Rocio
Seville, 41013
Canada3 sites
Bone Research and Education Center
Oakville, Ontario, L6M 1M1
CHU de Quebec Research Centre
Québec, G1V 4G2
Eastern Regional Health Authority Health Sciences Centre
St. John's, Newfoundland and Labrador, A1B 3V6
France3 sites
Hopital de la Conception-APHM
Marseille, 13385
CHU de Nantes - Hôtel-Dieu
Nantes, 44093
Hospital Bicetre AP-HP
Paris, 94275
Germany3 sites
Universitatsklinikum Carl Gustav Carus an der TU Dresden
Dresden, 01307
Medicover Neuroendokrinologie MVZ
Munich, 81667
Universitaetsklinikum Wuerzburg
Würzburg, 97080
Poland3 sites
Medycyny Nuklearnej i Chorob Wewnetrznych
Krakow, 30-688
Instytut Centrum Zdrowia Matki Polki. Klinika Endokrynologii Chorob Metabolicznych
Lodz, 93-338
Cendrum Zdrowi MDM - EB Group Sp.
Warsaw, 00189
United Kingdom3 sites
University Hospitals of Leicester NHS Trust
Leicester, LE1 5WW
Norfolk & Norwich University NHS Foundation Trust, Quadrum Institute
Norwich, NR4 7UQ
Churchill Hospital
Oxford, OX3 7LE
Denmark2 sites
Aarhaus University Hospital
Aarhus, 8200
Rigshospitalet
Copenhagen
Hungary2 sites
Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika
Budapest, 1083
Pecsi Tudomanyegyetem
Pécs, 7624
Netherlands2 sites
Leiden University Medical Center
Leiden, 2333
Eramus MC - University Medical Center
Rotterdam, 3015 GD
Portugal2 sites
Hospital da Luz Lisboa
Lisbon, 1500-650
Centro Hospital Vila Nova de Faia/Espinho
Porto, 4434-502
About this study
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)
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.
- Being tested
- eneboparatide, Placebo
- Keywords
- Hypoparathyroidism
- Medical subject headings
- Endocrine System Diseases, Parathyroid Diseases, Hypoparathyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eneboparatideCombination product
Also called AZP-3601
Supplied as a solution (concentration of 250 mcg/mL or 500 mcg/mL) in single-patient-use prefilled pens
PlaceboCombination product
Placebo is supplied as a solution (containing the excipient solution for eneboparatide) in single-patient-use prefilled pens
| Study group | Role | What they receive |
|---|---|---|
| eneboparatide | Experimental | Starting dose of 20 mcg; Administered once daily by subcutaneous injection Receives: Combination Product: eneboparatide |
| Placebo | Placebo comparator | Administered once daily by subcutaneous injection Receives: Combination Product: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 24 weeks
Secondary outcomes (5)
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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2023
- Study start7 Jun 2023
- Primary completion15 Nov 2024
- Study completion16 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic HypoparathyroidismStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Placebo-controlled, double-blind study, with patients randomized in a 2:1 ratio to receive eneboparatide or placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 165 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Amolyt Pharma
- Responsible party
- Sponsor
- Investigators
- Soraya Allas, MD, Study director, Amolyt Pharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05778071
- Sponsor's protocol ID
- AZP-3601-CLI-002
- Acronym
- CALYPSO
- Status last verified
- Sep 2025
- First submitted
- 9 Mar 2023
- Last updated
- 29 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05778071
- Acronym / sponsor ID
- CALYPSO / AZP-3601-CLI-002
- Keywords
- Hypoparathyroidism
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 165 participants (estimated)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Amolyt Pharma
- Study start
- 7 Jun 2023 (actual)
- Primary completion
- 15 Nov 2024 (actual)
- Study completion
- 16 Jun 2027 (estimated)
- First posted
- 21 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Placebo-controlled, double-blind study, with patients randomized in a 2:1 ratio to receive eneboparatide or placebo
| Arm | Type | Receives |
|---|---|---|
| eneboparatide | Experimental | Combination Product: eneboparatideStarting dose of 20 mcg; Administered once daily by subcutaneous injection |
| Placebo | Placebo comparator | Combination Product: PlaceboAdministered once daily by subcutaneous injection |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| eneboparatideAlso: AZP-3601Supplied as a solution (concentration of 250 mcg/mL or 500 mcg/mL) in single-patient-use prefilled pens | Combination product | eneboparatide |
| PlaceboPlacebo is supplied as a solution (containing the excipient solution for eneboparatide) in single-patient-use prefilled pens | Combination product | Placebo |
Primary outcome
Efficacy - Primary Endpoint
Time frame: 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).
5 secondary outcomes
Hypercalciuria
Time frame: 24 weeks
Change from baseline in the HPT-DD-SE - Physical Domain score
Time frame: 24 weeks
Change from baseline in the HPT-DD-SE - Cognitive Domain score
Time frame: 24 weeks
Change from baseline in the HPT-LIQ - Physical Functioning Domain score
Time frame: 24 weeks
Change from baseline in the SF-36 Physical Functioning subscore
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Soraya Allas, MD study director
Amolyt Pharma
54 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing eneboparatide in people with Chronic Hypoparathyroidism and Endocrine System Diseases, run by Alexion Pharmaceuticals, Inc. at 54 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 54 sites in United States, Japan, Italy, Spain, Canada and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy - Primary Endpoint (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2025.