NCT04701203|CompletedPhase 3ResultsFDA Drug

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

PaTHway

PaTHway TRIAL: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial, With an Open-Label Extension, Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Subcutaneously Daily in Adults With Hypoparathyroidism

Ascendis Pharma Bone Diseases A/S ClinicalTrials.gov

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2 other identifiers

TCP-3042020-003380-26

Study Type

interventional

Target

Locations

7 countries

Sites

Timeline

RegisteredJan 2021

StartedFeb 2021

CompletionJan 2025

Brief Summary

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_3

Timeline

Completed

Started Feb 2021

Typical duration for phase_3

Geographic Reach

7 countries

21 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3.9 years study duration

First Submitted

Initial submission to the registry

January 6, 2021

Completed

2 days until next milestone

First Posted

Study publicly available on registry

January 8, 2021

Completed

1 month until next milestone

Study Start

First participant enrolled

February 16, 2021

Completed

11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 12, 2022

Completed

3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 21, 2025

Completed

1 month until next milestone

Results Posted

Study results publicly available

February 28, 2025

Completed

Last Updated

February 9, 2026

Status Verified

January 1, 2026

Enrollment Period

11 months

First QC Date

January 6, 2021

Results QC Date

August 9, 2024

Last Update Submit

January 21, 2026

Conditions

Hypoparathyroidism Endocrine System Diseases Parathyroid Diseases

Keywords

HypoparathyroidismParathyroid HormoneTransCon PTHPTH(1-34)ProdrugSustained ReleaseParathyroid Hormone Replacement TherapyPalopegteriparatide

Outcome Measures

Primary Outcomes (1)

Efficacy - Primary Endpoint During the Blinded Period
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.
26 weeks

Secondary Outcomes (5)

Change From Baseline to Week 26 in HPES Symptom - Physical Domain Score
26 weeks
Change From Baseline to Week 26 in HPES Symptom - Cognitive Domain Score
26 weeks
Change From Baseline to Week 26 in HPES Impact - Physical Functioning Domain Score
26 weeks
Change From Baseline to Week 26 in HPES Impact - Daily Life Domain Score
26 weeks
Change From Baseline to Week 26 in SF-36 Physical Functioning Subscale Score
26 weeks

Study Arms (2)

TransCon PTH

EXPERIMENTAL

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

Combination Product: TransCon PTH

Placebo

PLACEBO COMPARATOR

Placebo for TransCon PTH delivered once daily by subcutaneous injection

Combination Product: Placebo

Interventions

TransCon PTHCOMBINATION_PRODUCT

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.

TransCon PTH

PlaceboCOMBINATION_PRODUCT

Placebo is supplied as a solution containing the formulation buffer for TransCon PTH in a single-patient-use prefilled pen intended for subcutaneous injection.

Placebo

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Males and females, ≥18 years of age
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
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
Optimization of supplements prior to randomization to achieve the target serum levels of:
(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
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)
BMI 17- 40 kg/m2 at Screening
If ≤25 years of age, radiological evidence of epiphyseal closure based on X-ray of nondominant wrist and hand
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
If treated with thyroid hormone replacement therapy, the dose must have been stable for at least 5 weeks prior to Screening
eGFR ≥30 mL/min/1.73 m2 during Screening
+2 more criteria

You may not qualify if:

Impaired responsiveness to PTH (pseudohypoparathyroidism) which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia
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
High risk thyroid cancer within 2 years, requiring suppression of TSH \<0.2 mIU/mL
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)
Use of thiazide diuretic within 4 weeks prior to the 24-hour urine collection scheduled to occur within 1 week prior to Visit 1
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
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
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
Non-hypocalcemic seizure disorder with a history of a seizure within 26 weeks prior to Screening
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
Pregnant or lactating women
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
Diagnosed drug or alcohol dependence within 3 years prior to Screening
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
Cerebrovascular accident within 5 years prior to Screening
+6 more criteria

Contact the study team to confirm eligibility.