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

• Register: ClinicalTrials.gov
• Last refreshed on: 10 March 2025
• Main ID: NCT04701203
• Date of registration: 06/01/2021
• Prospective Registration: Yes
• Primary sponsor: Ascendis Pharma Bone Diseases A/S
• Public title: A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Daily in Adults With Hypoparathyroidism PaTHway
• Scientific title: 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
• Date of first enrolment: February 16, 2021
• Target sample size: 84
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04701203
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

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

Contacts

• Name: Aimee D Shu, MD
• Affiliation: Ascendis Pharma A/S Medical Monitor/Medical Expert

Key inclusion & exclusion criteria

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


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Hypoparathyroidism

Parathyroid Diseases

Endocrine System Diseases

Intervention(s)

Combination Product: Placebo

Combination Product: TransCon PTH

Primary Outcome(s)

Efficacy - Primary Endpoint During the Blinded Period [Time Frame: 26 weeks]

Secondary Outcome(s)

Change From Baseline to Week 26 in HPES Symptom - Cognitive Domain Score [Time Frame: 26 weeks]

Change From Baseline to Week 26 in SF-36 Physical Functioning Subscale Score [Time Frame: 26 weeks]

Change From Baseline to Week 26 in HPES Impact - Physical Functioning Domain Score [Time Frame: 26 weeks]

Change From Baseline to Week 26 in HPES Symptom - Physical Domain Score [Time Frame: 26 weeks]

Change From Baseline to Week 26 in HPES Impact - Daily Life Domain Score [Time Frame: 26 weeks]

Secondary ID(s)

2020-003380-26

TCP-304

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/02/2025
• URL: https://clinicaltrials.gov/ct2/show/results/NCT04701203