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

NCT05778071 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AZP-3601-CLI-002
• Study Type: interventional
• Target: 165
• Locations: 13 countries
• Sites: 54

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.

Conditions

Chronic Hypoparathyroidism; Endocrine System Diseases; Parathyroid Diseases

Keywords

Hypoparathyroidism

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Hypercalciuria

  24 weeks

• Change from baseline in the HPT-DD-SE - Physical Domain score

  24 weeks

• Change from baseline in the HPT-DD-SE - Cognitive Domain score

  24 weeks

• Change from baseline in the HPT-LIQ - Physical Functioning Domain score

  24 weeks

• Change from baseline in the SF-36 Physical Functioning subscore

  24 weeks

Study Arms (2)

eneboparatide

EXPERIMENTAL

Starting dose of 20 mcg; Administered once daily by subcutaneous injection

Combination Product: eneboparatide

Placebo

PLACEBO COMPARATOR

Administered once daily by subcutaneous injection

Combination Product: Placebo

Interventions

eneboparatide COMBINATION_PRODUCT

Supplied as a solution (concentration of 250 mcg/mL or 500 mcg/mL) in single-patient-use prefilled pens

Also known as: AZP-3601

eneboparatide

Placebo COMBINATION_PRODUCT

Placebo is supplied as a solution (containing the excipient solution for eneboparatide) in single-patient-use prefilled pens

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• (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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead
• Amolyt Pharma: collaborator

Study Sites (54)

Harbor UCLA Medical Center Endocrinology

Torrance, California, 90502, United States

Location

Denver Endocrinology Diabetes and Thyroid Center

Denver, Colorado, 80113, United States

Location

University of Chicago - Medical Center

Chicago, Illinois, 60637, United States

Location

North Shore University Health System

Evanston, Illinois, 60201, United States

Location

Indiana University (IU) Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Northern Nevada Endocrinology

Reno, Nevada, 89511, United States

Location

Colombia University Irving Medical Center

New York, New York, 10032, United States

Location

Physician's East Endocrinology

Greenville, North Carolina, 27834, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

The Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

Location

The Children's Hospital of Philadephia

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Academy of Diabetes, Thyroid and Endocrine

El Paso, Texas, 79935, United States

Location

Arthritis Northwest, PLLC

Spokane, Washington, 99204, United States

Location

Eastern Regional Health Authority Health Sciences Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Bone Research and Education Center

Oakville, Ontario, L6M 1M1, Canada

Location

CHU de Quebec Research Centre

Québec, G1V 4G2, Canada

Location

Aarhaus University Hospital

Aarhus, 8200, Denmark

Location

Rigshospitalet

Copenhagen, Denmark

Location

Hopital de la Conception-APHM

Marseille, 13385, France

Location

CHU de Nantes - Hôtel-Dieu

Nantes, 44093, France

Location

Hospital Bicetre AP-HP

Paris, 94275, France

Location

Universitatsklinikum Carl Gustav Carus an der TU Dresden

Dresden, 01307, Germany

Location

Medicover Neuroendokrinologie MVZ

Munich, 81667, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97080, Germany

Location

Semmelweis Egyetem Belgyogyaszati es Hematologiai Klinika

Budapest, 1083, Hungary

Location

Pecsi Tudomanyegyetem

Pécs, 7624, Hungary

Location

Azienda Ospedaliero Universitaria de Bologna, Policlinico Sant Orsola Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, 20122, Italy

Location

Azienda Ospedaliera Universitaria Pisana-Ospedale di Cisanello

Pisa, 56124, Italy

Location

Via Alvaro del Portillo, 200, Roma, Italy 00128

Roma, 00128, Italy

Location

Teikyo University Chiba Medical Center

Chiba, Japan

Location

Kanazawa University Hospital

Kanazawa, Japan

Location

Osaka City Hospital

Osaka, Japan

Location

Osaka Metropolital University Hospital

Osaka, Japan

Location

Tokushima University Hospital

Tokushima, Japan

Location

Tottori University Hospital

Tottori, Japan

Location

Leiden University Medical Center

Leiden, 2333, Netherlands

Location

Eramus MC - University Medical Center

Rotterdam, 3015 GD, Netherlands

Location

Medycyny Nuklearnej i Chorob Wewnetrznych

Krakow, 30-688, Poland

Location

Instytut Centrum Zdrowia Matki Polki. Klinika Endokrynologii Chorob Metabolicznych

Lodz, 93-338, Poland

Location

Cendrum Zdrowi MDM - EB Group Sp.

Warsaw, 00189, Poland

Location

Hospital da Luz Lisboa

Lisbon, 1500-650, Portugal

Location

Centro Hospital Vila Nova de Faia/Espinho

Porto, 4434-502, Portugal

Location

Complejo Hospitalario Universitario de A Coruna

A Coruña, 15006, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

University Hospitals of Leicester NHS Trust

Leicester, LE1 5WW, United Kingdom

Location

Norfolk & Norwich University NHS Foundation Trust, Quadrum Institute

Norwich, NR4 7UQ, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Endocrine System Diseases; Parathyroid Diseases; Hypoparathyroidism

Study Officials

• Soraya Allas, MD

  Amolyt Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo-controlled, double-blind study, with patients randomized in a 2:1 ratio to receive eneboparatide or placebo

Study Record Dates

• First Submitted: March 9, 2023
• First Posted: March 21, 2023
• Study Start: June 7, 2023
• Primary Completion: November 15, 2024
• Study Completion (Estimated): June 16, 2027
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

US (16); PL (3); PT (2); GB (3); CA (3); IT (5); DK (2); DE (3); ES (4); FR (3); HU (2); JP (6); NL (2)