PaTHway CHINA TRIAL: A Trial to Investigating the Safety, Tolerability and Efficacy of TransCon PTH in Adults With Hypoparathyroidism

Not Provided

Inclusion criteria

• 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 (below the ULN of local laboratory) serum PTH levels.
• Requirement for doses of SoC (e.g., calcitriol, alfacalcidol, calcium supplements) at or above a minimum threshold:

• 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, and calcium should be stable for at least 5 weeks prior to Screening
• Optimization of supplements prior to randomization to achieve the target serum levels of:

• 25(OH) vitamin D levels of 10-100 ng/mL (25-250 nmol/L) and
• Magnesium level in the normal range, or just below the normal range i.e.: ≥1.3 mg/dL (0.53 mmol/L) and
• Albumin-adjusted sCa level in the normal range, or just below the normal range, i.e.: 7.8-10.6 mg/dL (or 1.95-2.64 mmol/L)
• 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 non-dominant 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/L
• 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
• Able to perform daily SC self-injections of study drug (or have a designee to perform injections) via a pre-filled injection pen
• Able and willing to provide written and signed ICF in accordance with GCP

Exclusion criteria

• 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 non-melanoma skin cancer); active hyperparathyroidism; parathyroid carcinoma within 5 years prior to Screening; acromegaly;or multiple endocrine neoplasia
• High risk thyroid cancer within 2 years, requiring suppression of TSH <0.2 mIU/L
• Long term 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
• 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 mm Hg in the setting of white coat hypertension/anxiety may not be exclusionary and a measurement can be repeated prior to randomization
• Cerebrovascular accident within 5 years prior to Screening
• Within 26 weeks prior to Screening: acute colic due to nephrolithiasis, or acute gout. Subjects with asymptomatic renal stones are permitted
• 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
• 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
• Known allergy or sensitivity to PTH or any of the excipients [metacresol, mannitol, succinic acid, NaOH/(HCl)]
• Likely to be non-compliant with respect to trial conduct
• Any other reason that in the opinion of the investigator would prevent the subject from completing participation or following the trial schedule