Palopegteriparatide in Chronic Hypoparathyroidism (PaTHreal)

January 23, 2026 updated by: Maria Yavropoulou, National and Kapodistrian University of Athens

Real-World Data for Effectiveness and Safety of Palopegteriparatide in Patients With Chronic Hypoparathyroidism in Greece

This is a multicenter, prospective cohort study conducted across 9 tertiary and university hospitals in the rural area of Athens, which investigates the clinical and biochemical effects of palopegteriparatide (TransCon PTH) in adult patients with chronic hypoparathyroidism (≥12 months). Eligible participants included those transitioning from conventional therapy (activated vitamin D analogs and oral calcium) and those previously treated with rhPTH(1-84). The primary objective was to assess the time to independence from activated vitamin D and calcium supplementation. Secondary objectives included changes in biochemical parameters, incidence of clinically significant hypo- and hypercalcemia during the titration period , and reduction in daily pill burden. Patients received individualized doses of palopegteriparatide with follow-up visits at regular intervals, and safety was monitored throughout the study according to standard clinical practice.

Study Overview

Status

Completed

Conditions

Detailed Description

2. Subjects and Methods 2.1 Study Design and Setting

This was a multicenter, prospective cohort study conducted across 9 tertiary and university hospitals in the rural area of Athens. Eligible participants were enrolled from specialized centers experienced in the management of HypoPT between the date that palopegteriparatide was commercially available in Greece (first patient initiating palopegteriparatide was in June 2024) and September 2025. The study included two predefined patient cohorts:

  1. Individuals transitioning from conventional therapy (activated vitamin D analogs and calcium supplementation), and
  2. Individuals previously treated with rhPTH(1-84) before switching to palopegteriparatide.

2.1.1Participants Adult patients (≥18 years) with a confirmed diagnosis of chronic hypoparathyroidism (HypoPT) of at least 12 months' duration who initiated palopegteriparatide (TransCon PTH)were eligible for inclusion. All participants fulfilled the criteria for PTH replacement therapy as defined by the Hellenic Endocrine Society guidelines.

Diagnosis of chronic HypoPT was established by persistent hypocalcemia in conjunction with inappropriately low or normal serum parathyroid hormone (PTH) concentrations.

Patients were considered eligible for PTH replacement therapy when conventional management failed to achieve optimal biochemical or clinical control, defined by one or more of the following:

  • Persistent hypocalcemia or hypocalcemic symptoms despite high-dose oral calcium and active vitamin D supplementation.
  • Significant hypercalciuria, nephrolithiasis, nephrocalcinosis, or other renal complications associated with conventional therapy.

To be included in the present analysis, participants were required to have received palopegteriparatide treatment for at least one month prior to data collection or evaluation Exclusion criteria were i) transient postsurgical HypoPT, ii) severe renal impairment (eGFR < 30 mL/min/1.73 m²), iii) active malignancy, iv) Individuals with impaired responsiveness to PTH (pseudohypoparathyroidism)or any disease that might affect calcium metabolism, phosphate metabolism or PTH levels other than hypoparathyroidism, v) other drugs known to influence calcium and bone metabolism (except for activated vitamin D analogs and elemental calcium) such as osteoporosis therapies or glucocorticoids (other than as replacement therapy).

Access to palopegteriparatide in Greece is currently through the National Organization for the Provision of Health Services (EOPYY), which manages reimbursed outpatient and hospital medicines. Medicines for rare diseases or high-cost therapies require pre-approval by relevant health committees. Palopegteriparatide is classified as high-cost medicines and is fully reimbursed upon approval. Continued reimbursement depends on documented treatment response, reductions in conventional therapy burden, control of calcium/urine parameters, and absence of unacceptable adverse events.

2.1.2Treatment Protocol Independent of the last rhPTH(1-84) dose, all patients initiating TransCon PTH were started on 18 µg once daily, as recommended by the manufacturer. The dose was titrated individually based on serum calcium levels, and clinical response, following real-world clinical practice and the product's prescribing information. Concomitant calcium and activated vitamin D supplementation were adjusted or discontinued at the treating physician's discretion to maintain serum calcium within the lower half of the normal range and to minimize hypercalciuria (defined as >250 mg/day in women, >300 mg/day in men, or >4 mg/kg/day in both genders).

2.2 Data Collection and Assessments Baseline data included demographic characteristics, etiology and duration of HypoPT, biochemical parameters (serum calcium, phosphate, magnesium, 25(OH)D, creatinine, and 24-hour urinary calcium), medication use, and comorbidities. Follow-up visits were scheduled at regular intervals according to each center's clinical routine. At each visit, biochemical measurements were recorded, and changes in calcium and vitamin D supplementation, TransCon PTH dose adjustments, and adverse events were documented.

2.3 Ethical Considerations The study protocol was approved by the institutional review boards of all participating centers and conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants prior to enrollment.

2.4 Study endpoints 2.4.1 Primary Endpoint The primary endpoint was the time to achievement of independence from activated vitamin D and oral calcium supplementation following initiation of palopegteriparatide. Independence was defined as the absence of any activated vitamin D or calcium supplementation for at least four consecutive weeks, without any increase in the palopegteriparatide dose during that period.

2.4.2 Secondary Endpoints

Secondary endpoints included:

I. The proportion of patients achieving independence from activated vitamin D and calcium within the 14-month observation period.

II. Changes in biochemical parameters (serum calcium, phosphate, magnesium, creatinine, estimated glomerular filtration rate [eGFR], calcium-phosphate product, and 24-hour urinary calcium) between baseline (before initiating palopegteriparatide) and the last follow-up visit.

III. Incidence of clinically significant hypo- and hypercalcemia requiring hospitalization during the study period.

IV. Change in daily pill burden, calculated as the total number of oral calcium and activated vitamin D tablets per day at baseline and last follow-up visit.

2.5. Safety Assessments Safety evaluations were conducted at prespecified intervals, typically every two-three months, in accordance with standard care of clinical practice. Data collected included concomitant medication use, serum biochemistry, hematology, and 25-hydroxyvitamin D levels. Twenty-four-hour urinary calcium excretion was measured periodically. Clinical events such as symptomatic hypo- or hypercalcemia were recorded, and all adverse events deemed treatment-related were documented according to the judgment of the treating physician.

2.6. Statistical Analysis Clinical and biochemical data were analyzed using descriptive and inferential statistics. Categorical variables were presented as absolute numbers and percentages, while continuous variables were expressed as means ± standard deviation (SD) or medians (interquartile range, IQR) where appropriate, depending on data distribution. Normality of distribution was assessed using the Shapiro-Wilk test and inspection of histograms.

To evaluate the effect of palopegteriparatide treatment on biochemical and clinical parameters, within-subject comparisons were performed between baseline (pre-treatment) and the last available follow-up measurement.Τhe paired t-test or the Wilcoxon signed-rank test was applied to compare mean values before and after treatment, as applicable. To explore associations between time to independence from supplements, and biochemical parameters at baseline, duration of the disease or pill burden at baseline, correlation analyses were performed, using Pearson's correlation coefficient (r) or Spearman's rank correlation coefficient (rho), as applicable.

All statistical tests were two-sided, with a significance level of α = 0.05. Confidence intervals (CIs) were two-sided 95%, unless otherwise specified. Analyses were performed using IBM SPSS Statistics (version 28; IBM Corp., Armonk, NY, USA), or equivalent validated statistical software.

Study Type

Observational

Enrollment (Actual)

90

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
    • Attica
      • Athens, Attica, Greece, 11527
        • Laiko General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult patients (≥18 years) with a confirmed diagnosis of chronic hypoparathyroidism (HypoPT) of at least 12 months' duration who initiated palopegteriparatide (TransCon PTH)

Description

Inclusion Criteria:

  • Adult patients (≥18 years) with a confirmed diagnosis of chronic hypoparathyroidism (HypoPT) of at least 12 months' duration who initiated palopegteriparatide (TransCon PTH)

Exclusion Criteria:

  • i) transient postsurgical HypoPT ii) severe renal impairment (eGFR < 30 mL/min/1.73 m²) iii) active malignancy iv) Individuals with impaired responsiveness to PTH (pseudohypoparathyroidism) or any disease that might affect calcium metabolism, phosphate homeostasis, or PTH levels other than hypoparathyroidism v) other drugs known to influence calcium and bone metabolism (except for activated vitamin D analogs and elemental calcium) such as osteoporosis therapies or glucocorticoids other than as replacement therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Chronic hypoparathyroidism patients treated with palopegteriparatide
Adult patients with chronic hypoparathyroidism (≥12 months) initiating treatment with palopegteriparatide (TransCon PTH). The cohort includes patients transitioning from conventional therapy (activated vitamin D and calcium supplementation) as well as patients previously treated with rhPTH(1-84). Palopegteriparatide doses were individually titrated based on serum calcium levels and clinical response. Concomitant calcium and activated vitamin D supplementation were adjusted or discontinued according to the treating physician's discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to achievement of independence from activated vitamin D and oral calcium supplementation
Time Frame: From June 2024 (commercial availability of palopegteriparatide in Greece) through September 2025 (end of observation period).
The primary endpoint was the time to achievement of independence from activated vitamin D and oral calcium supplementation following initiation of palopegteriparatide. Independence was defined as the absence of any activated vitamin D or calcium supplementation for at least four consecutive weeks, without any increase in the palopegteriparatide dose during that period.
From June 2024 (commercial availability of palopegteriparatide in Greece) through September 2025 (end of observation period).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical and Biochemical Outcomes Following Palopegteriparatide Treatment in HypoPT Patients
Time Frame: From June 2024 (commercial availability of palopegteriparatide in Greece) through September 2025 (end of observation period).
I. The proportion of patients achieving independence from activated vitamin D and calcium within the 14-month observation period.
From June 2024 (commercial availability of palopegteriparatide in Greece) through September 2025 (end of observation period).
II. To asses changes in albumin corrected calcium levels between baseline and last visit
Time Frame: baseline to last visit within the 14 months of treatmemt
baseline to last visit within the 14 months of treatmemt
II. To asses changes in phosphate levels between baseline and last visit
Time Frame: baseline to last visit within the 14 months of treatmemt
baseline to last visit within the 14 months of treatmemt
II. To asses changes in calcium 24 hour urine levels between baseline and last visit
Time Frame: baseline to last visit within the 14 months of treatmemt
baseline to last visit within the 14 months of treatmemt
II. To asses changes in magnesium levels between baseline and last visit
Time Frame: baseline to last visit within the 14 months of treatmemt
baseline to last visit within the 14 months of treatmemt

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National and Kapodistrian University of Athens

Collaborators

Hippocration General Hospital
Alexandra Hospital, Athens, Greece
251 Hellenic Air Force & VA General Hospital
G.Gennimatas General Hospital
Laikο General Hospital, Athens
Theagenio Cancer Hospital
Hellenic Red Cross Hospital
KAT Hospital of Athens
Evaggelismos Hospital, Greece

Investigators

  • Principal Investigator: Eva Kassi, M.D, Medical School, National and Kapodistrian University of Athens, LAIKO University Hospital of Athens
  • Study Director: Symeon Tournis, M.D, Laboratory for Research of the Musculoskeletal System "Th. Garofalidis", Medical School, National and Kapodistrian University of Athens, KAT Hospital, 10 Athinas Str, Kifissia, Athens,
  • Study Director: Fotini Adamidou, M.D, Department of Endocrinology and Diabetes, Hippokratio General Hospital, Thessaloniki, Greece.
  • Study Director: Zoe Efstathiadou, MD, Department of Endocrinology and Diabetes, Hippokratio General Hospital, Thessaloniki, Greece.
  • Study Director: Andromachi Vryonidou, M.D, Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece.
  • Study Director: Polyzois Makras, M.D, Department of Endocrinology and Diabetes, Department of Medical Research, 251 Hellenic Air Force General Hospital, Athens, Greece
  • Study Director: Dimos Florakis, M.D., Department of Endocrinology, Metropolitan General Hospital, Athens, Greece.
  • Study Director: Alexandra Chrisoulidou, M.D, Department of Endocrinology, Theagenio Cancer Hospital, 54639 Thessaloniki, Greece.
  • Study Director: Theodora Stratigou, M.D, Department of Endocrinology and First Department of Internal Medicine, 'Evangelismos' General Hospital of Athens, Athens, Greece.
  • Study Director: Irene Giagourta, M.D, Unit of Endocrinology, and Diabetes Center, 'G. Gennimatas' General Hospital of Athens, Athens, Greece.
  • Principal Investigator: Maria Yavropoulou, M.D, Medical School, National and Kapodistrian University of Athens, LAIKO University Hospital of Athens

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2024

Primary Completion (Actual)

September 30, 2025

Study Completion (Actual)

October 23, 2025

Study Registration Dates

First Submitted

November 25, 2025

First Submitted That Met QC Criteria

December 17, 2025

First Posted (Actual)

December 23, 2025

Study Record Updates

Last Update Posted (Actual)

January 26, 2026

Last Update Submitted That Met QC Criteria

January 23, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 257

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Due to participant privacy concerns and institutional policies, individual participant data will not be shared outside the research team

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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