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Trial · Interventional

CompletedPhase 3Results postedRegistry data

A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Daily in Adults With Hypoparathyroidism

Short name PaTHway

NCTNCT04701203 (opens ClinicalTrials.gov in a new tab)Other idTCP-304Other id2020-003380-26

Overview

Status
Completed
Phase
Phase 3
Enrollment
84 participants (actual)
Sponsor
Ascendis Pharma Bone Diseases A/S · Industry
Design
Randomized · Quadruple masking
Countries
7 countries

United States, Canada, Denmark, Germany, Hungary, Italy, Norway

Start
16 Feb 2021
Primary completion
12 Jan 2022
Completion
21 Jan 2025
First posted
8 Jan 2021
Last update posted
7 Jul 2026
Conditions
Hypoparathyroidism · Endocrine System Diseases · Parathyroid Diseases

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
202120222023202420252026
  1. Ph 3

    PaTHway

    NCT04701203

    16 Feb 2021 to 21 Jan 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

During the first 26 weeks of the trial, participants were randomly assigned to one of two groups: one group received TransCon PTH and one group received placebo. All participants started with study drug at a dose of 18 mcg/day and were individually and progressively titrated to an optimal dose in dose increments of 3 mcg/day. TransCon PTH or placebo were administered as a subcutaneous injection using a pre-filled injection pen. Neither trial participants nor their doctors knew who had been assigned to each group. After the 26 weeks, participants continued in the trial as part of a long-term extension study. During the extension, all participants received TransCon PTH, with the dose adjusted to their individual needs. This was a global trial that was conducted in the United States, Canada, Germany, Denmark, Norway, Italy, and Hungary.

Interventions

  • TransCon PTHCombination product
  • PlaceboCombination product

Arms2

  • Experimental

    TransCon PTH

    TransCon PTH at a starting dose of 18 mcg delivered once daily by subcutaneous injection and titrated to an optimal dose

  • Placebo comparator

    Placebo

    Placebo for TransCon PTH delivered once daily by subcutaneous injection

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Efficacy - Primary Endpoint During the Blinded Period

    Time frame · 26 weeks

    Registry description

    The primary endpoint was a multi-component endpoint that included the percentage of participants who met the following criteria at 26 weeks of blinded treatment: 1) albumin-adjusted serum calcium measured within 4 weeks prior to and on Week 26 visit within the normal range (8.3 to 10.6 mg/dL), and 2) independence from active vitamin D within 4 weeks prior to Week 26 visit (i.e., all daily standing dose of active vitamin D equal to zero AND use of PRN ≤7 days during the 4 weeks), and 3) independence from therapeutic doses of calcium within 4 weeks prior to Week 26 visit (i.e., average daily standing dose of elemental calcium ≤600 mg AND use of PRN doses on ≤7 days during the 4 weeks), and 4) no increase in prescribed study drug within 4 weeks prior to Week 26 visit.

Secondary outcomes(5)
  1. Change From Baseline to Week 26 in HPES Symptom - Physical Domain Score

    Time frame · 26 weeks

    Registry description

    Change from baseline in Hypoparathyroidism Patient Experience Scale (HPES) Symptom - Physical Domain score, a disease-specific patient reported outcome, at 26 weeks of treatment. The measure uses a scale of 0-100 and values represent the change in scores from baseline. A decrease in HPES score denotes an improvement in hypoparathyroidism disease related physical symptoms.

  2. Change From Baseline to Week 26 in HPES Symptom - Cognitive Domain Score

    Time frame · 26 weeks

    Registry description

    Change from baseline in Hypoparathyroidism Patient Experience Scale (HPES) Symptom - Cognitive Domain score, a disease-specific patient reported outcome, at 26 weeks of treatment. The measure uses a scale of 0-100 and values represent the change in scores from baseline. A decrease in HPES score denotes an improvement in hypoparathyroidism disease related cognitive symptoms.

  3. Change From Baseline to Week 26 in HPES Impact - Physical Functioning Domain Score

    Time frame · 26 weeks

    Registry description

    Change from baseline in Hypoparathyroidism Patient Experience Scale (HPES) Impact - Physical Functioning Domain score, a disease-specific patient reported outcome, at 26 weeks of treatment. The measure uses a scale of 0-100 and values represent the change in scores from baseline. A decrease in HPES score denotes an improvement in physical functioning health-related quality of life.

  4. Change From Baseline to Week 26 in HPES Impact - Daily Life Domain Score

    Time frame · 26 weeks

    Registry description

    Change from baseline in Hypoparathyroidism Patient Experience Scale (HPES) Impact - Daily Life Domain score, a disease-specific patient reported outcome, at 26 weeks of treatment. The measure uses a scale of 0-100 and values represent the change in scores from baseline. A decrease in HPES score denotes an improvement in daily health-related quality of life.

  5. Change From Baseline to Week 26 in SF-36 Physical Functioning Subscale Score

    Time frame · 26 weeks

    Registry description

    Change from baseline in the 36-item Short Form Survey (SF-36) Physical Functioning subscale score, a generic health survey, at 26 weeks of treatment. The Physical Functioning subscale uses a range of 19-57.6 and values represent the change in scores from baseline. An increase in SF-36 score denotes an improvement in physical functioning health-related quality of life.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· 26 weeks

Efficacy - Primary Endpoint During the Blinded Period

GroupValue (Percentage of participants)
TransCon PTH78.7
Placebo4.8
Secondary and other outcome results(5)
Secondary outcomeLeast squares mean· 26 weeks

Change From Baseline to Week 26 in HPES Symptom - Physical Domain Score

GroupValue (units on a scale)
TransCon PTH-21.01
Placebo-4.81
Secondary outcomeLeast squares mean· 26 weeks

Change From Baseline to Week 26 in HPES Symptom - Cognitive Domain Score

GroupValue (units on a scale)
TransCon PTH-20.49
Placebo-6.16
Secondary outcomeLeast squares mean· 26 weeks

Change From Baseline to Week 26 in HPES Impact - Physical Functioning Domain Score

GroupValue (units on a scale)
TransCon PTH-18.29
Placebo-1.01
Secondary outcomeLeast squares mean· 26 weeks

Change From Baseline to Week 26 in HPES Impact - Daily Life Domain Score

GroupValue (units on a scale)
TransCon PTH-17.65
Placebo-0.36
Secondary outcomeLeast squares mean· 26 weeks

Change From Baseline to Week 26 in SF-36 Physical Functioning Subscale Score

GroupValue (units on a scale)
TransCon PTH5.29
Placebo0.12

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Double Blind: TransCon PTHTransCon PTH at a starting dose of 18 mcg delivered once daily by subcutaneous injection and titrated to an optimal dose during the blinded period TransCon PTH: TransCon PTH drug product is supplied as a solution with a concentration of 0.3 mg PTH(1-34)/mL in a single-patient-use prefilled pen intended for subcutaneous injection.1 / 615 / 6150 / 61
Double Blind: PlaceboPlacebo for TransCon PTH delivered once daily by subcutaneous injection during the blinded period Placebo: Placebo is supplied as a solution containing the formulation buffer for TransCon PTH in a single-patient-use prefilled pen intended for subcutaneous injection.0 / 212 / 2120 / 21
Total TransCon PTH PeriodParticipants who completed the 26-week double blind treatment period in placebo and TransCon PTH groups, continued into the open-label extension period and received treatment with TransCon PTH up to Week 182. This period refers to total period of exposure to TransCon PTH. For participants randomized to TransCon PTH at enrollment, the "TransCon PTH Period" was the time from first dose of blinded TransCon PTH until final analysis in OLE period. The TransCon PTH Period for participants randomized to placebo at enrollment was the time from first exposure to TransCon PTH at the time of cross-over from placebo, until final analysis in the OLE period.1 / 8020 / 8072 / 80

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

Studies with results

2 studies on this page

Indexing hint: Randomized controlled trial · 2024

8 results

Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial.

Rejnmark et al. 2024Advances in therapycited by 33

PMID 38691316PMC11133178DOI 10.1007/s12325-024-02843-8PUB-38691316

Free to read · publisher termsCC BY-NC8 results

Indexing hint: Randomized controlled trial · 2024

16 results

Measuring treatment impacts on symptoms in adults with hypoparathyroidism: findings from the PaTHway trial.

Brod et al. 2024Journal of patient-reported outcomescited by 2

PMID 39136801PMC11322464DOI 10.1186/s41687-024-00757-1PUB-39136801

CC BY16 results

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. Males and females, ≥18 years of age 2. Subjects with postsurgical chronic HP, or auto-immune, genetic, or idiopathic HP for at least 26 weeks. Diagnosis of HP is established based on historic hypocalcemia in the setting of inappropriately low serum PTH levels 3. Requirement for doses of SoC (e.g., calcitriol, alfacalcidol, calcium supplements) at or above a minimum threshold: * For countries other than Japan: requirement for a dose of calcitriol ≥0.5 μg/day, or alfacalcidol ≥1.0 μg/day and (elemental) calcium ≥800 mg/day (e.g., calcium citrate, calcium carbonate etc.) for at least 12 weeks prior to Screening. In addition, the dose of calcitriol, or alfacalcidol, or calcium should be stable for at least 5 weeks prior to Screening * For Japan: requirement for a dose of calcitriol ≥1.0 μg/day, or alfacalcidol ≥2.0 μg/day for at least 12 weeks prior to Screening. In addition, the dose of calcitriol or alfacalcidol should be stable for at least 5 weeks prior to Screening. In Japan only (due to local practice and dietary patterns), there is no requirement to exceed a minimum dose of calcium supplements 4. Optimization of supplements prior to randomization to achieve the target serum levels of: * 25(OH) vitamin D levels of 20-80 ng/mL (49-200 nmol/L) and * Magnesium level in the normal range, or just below the normal range and * Albumin-adjusted or ionized sCa level in the normal range, or just below the normal range 5. The subject demonstrates a 24-hour uCa excretion of ≥125 mg/24h (on a sample collected within 52 weeks prior to Screening or during the Screening Period) 6. BMI 17- 40 kg/m2 at Screening 7. If ≤25 years of age, radiological evidence of epiphyseal closure based on X-ray of nondominant wrist and hand 8. Thyroid-stimulating hormone (TSH) within normal laboratory limits within the 6 weeks prior to Visit 1; if on suppressive therapy for a history of thyroid cancer, TSH level must be ≥0.2 mIU/mL 9. If treated with thyroid hormone replacement therapy, the dose must have been stable for at least 5 weeks prior to Screening 10. eGFR ≥30 mL/min/1.73 m2 during Screening 11. Able to perform daily subcutaneous self-injections of study drug (or have a designee to perform injections) via a pre-filled injection pen 12. Able and willing to provide written and signed informed consent in accordance with GCP Exclusion Criteria: 1. Impaired responsiveness to PTH (pseudohypoparathyroidism) which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia 2. Any disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than HP, such as active hyperthyroidism; Paget disease of bone; severe hypomagnesemia; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1C \>9%, documented HbA1C result drawn within 12 weeks prior to Screening is acceptable); severe and chronic liver, or renal disease; Cushing syndrome; multiple myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy (other than low-risk well differentiated thyroid cancer or basal cell skin cancer); active hyperparathyroidism; parathyroid carcinoma within 5 years prior to Screening; acromegaly; or multiple endocrine neoplasia types 1 and 2 3. High risk thyroid cancer within 2 years, requiring suppression of TSH \<0.2 mIU/mL 4. Use of loop diuretics, phosphate binders (other than calcium supplements), digoxin, lithium, methotrexate, biotin \>30 μg/day, or systemic corticosteroids (other than as replacement therapy) 5. Use of thiazide diuretic within 4 weeks prior to the 24-hour urine collection scheduled to occur within 1 week prior to Visit 1 6. Use of PTH-like drugs (whether commercially available or through participation in an investigational trial), including PTH(1-84), PTH(1-34), or other N-terminal fragments or analogs of PTH or PTH-related protein, within 4 weeks prior to Screening 7. Use of other drugs known to influence calcium and bone metabolism, such as calcitonin, fluoride tablets (\>0.5 mg/day), strontium, or cinacalcet hydrochloride, within 12 weeks prior to Screening 8. Use of osteoporosis therapies known to influence calcium and bone metabolism, i.e., bisphosphonate (oral or intravenous \[IV\]), denosumab, raloxifene, or romosozumab therapies within 2 years prior to Screening 9. Non-hypocalcemic seizure disorder with a history of a seizure within 26 weeks prior to Screening 10. Increased risk for osteosarcoma, such as those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, hereditary disorders predisposing to osteosarcoma, or with a prior history of substantial external beam or implant radiation therapy involving the skeleton 11. Pregnant or lactating women 12. Male who has a female partner who intends to become pregnant or is of childbearing potential and is unwilling to use adequate contraceptive methods during the trial 13. Diagnosed drug or alcohol dependence within 3 years prior to Screening 14. Disease processes that adversely affect gastrointestinal absorption, including but not limited to short bowel syndrome, significant small bowel resection, gastric bypass, tropical sprue, active celiac disease, active ulcerative colitis, active Crohn's disease, gastroparesis and AIRE gene mutations with malabsorption 15. Chronic or severe cardiac disease within 26 weeks prior to Screening including but not limited to congestive heart failure, myocardial infarction, severe or uncontrolled arrhythmias, bradycardia (resting heart rate \<48 beats/minute, unless chronic and asymptomatic), symptomatic hypotension or systolic BP \<80 mm Hg or diastolic \<40 mm Hg or poorly controlled hypertension (systolic BP \>165 mm Hg or diastolic \>95 mm Hg). In the absence of a prior history of hypertension, an isolated BP \>165/95 in the setting of white coat hypertension/anxiety may not be exclusionary and a measurement can be repeated prior to randomization 16. Cerebrovascular accident within 5 years prior to Screening 17. Within 26 weeks prior to Screening: acute colic due to nephrolithiasis, or acute gout. Subjects with asymptomatic renal stones are permitted 18. Participation in any other interventional trial in which receipt of investigational drug or device occurred within 8 weeks (or within 5.5 times the half-life of the investigational drug (whichever comes first) prior to Screening 19. 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 investigational product or procedures, including treated malignancies that are likely to recur within the approximate 3.5-year duration of the trial 20. Known allergy or sensitivity to PTH or any of the excipients \[metacresol, mannitol, succinic acid, NaOH/(HCl)\] 21. Likely to be non-compliant with respect to trial conduct 22. Any other reason that in the opinion of the investigator would prevent the subject from completing participation or following the trial schedule

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