NIPH Clinical Trials Search

JAPANESE
国立保健医療科学院
JRCT ID: jRCT2051210058

Registered date:30/07/2021

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

Basic Information

Recruitment status Not Recruiting
Health condition(s) or Problem(s) studiedHypoparathyroidism
Date of first enrollment02/11/2021
Target sample size12
Countries of recruitment
Study typeInterventional
Intervention(s)TransCon PTH drug product is supplied as a solution with a concentration of 0.3 mg/mL in a single-patient-use prefilled pen intended for SC injection. All subjects will start with study drug 18 microgram/day and will be administered study drug once daily subcutaneously. Subjects will be individually and progressively titrated to an optimal dose in dose increments (increase or decrease) of 3 microgram/day.

Outcome(s)

Primary OutcomeAt 26 weeks of treatment, the proportion of subjects with: - Albumin-adjusted serum Ca(sCa) within the normal range (8.3-10.6mg/dL), and - Independence from active vitamin D and - Independence from therapeutic doses of calcium(i.e., taking calcium supplements <=600 mg/day).
Secondary Outcome- Change from baseline in 36-Item Short Form Survey (SF-36)(at 26 weeks of treatment) - Calcium and active vitamin D doses - Daily "pill burden" of active vitamin D and calcium (as oral tablets, powder, liquid solutions, liquid suspensions, or transdermal patches) - serum phosphate(sP) - Albumin-adjusted sCa x sP product, including proportion of subjects with albumin-adjusted sCa x sP product <=55 mg^2/dL^2, <=52 mg^2/dL^2, and <=44 mg^2/dL^2 - Albumin-adjusted sCa - BMD and TBS by DXA - Bone turnover markers (serum P1NP and CTx) - serum Magnesium - Clinical Global Impression of Severity

Key inclusion & exclusion criteria

Age minimum>= 18age old
Age maximumNot applicable
GenderBoth
Include criteria1. Males and females, at least 18 years-old 2. Subjects with postsurgical chronic hypoparathyroidism(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 a dose of calcitriol >=1.0 microgram/day, or alfacalcidol >=2.0 microgram/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. 4. Optimization of supplements prior to Visit 1 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 i.e.: >=1.3 mg/dL (0.53 mmol/L) and - Albumin-adjusted or ionized serum Ca(sCa) level in the normal range, or just below the normal range - Albumin-adjusted sCa 7.8-10.6 mg/dL (or 1.95-2.64 mmol/L) - Ionized sCa 4.40-5.29 mg/dL (or 1.10-1.32 mmol/L) 5. The subject demonstrates a 24-hour urine Ca(uCa) excretion of >=125 mg/24h (on a sample collected within 52 weeks prior to Screening or during the Screening Period) 6. Body mass index (BMI) 17- 40 kg/m^2 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/L 9. If treated with thyroid hormone replacement therapy, the dose must have been stable for at least 5 weeks prior to Screening 10. Estimated glomerular filtration rate (eGFR) >=30 mL/min/1.73 m^2 during Screening 11. Able to perform daily subcutaneous self-injections of TransCon PTH (or have a designee to perform injections) via a pre-filled injection pen 12. Able and willing to provide written and signed Informed Consent Form in accordance with Good Clinical Practice .
Exclude criteria1. 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 non-melanoma 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/L 4. Use of loop diuretics, phosphate binders (other than calcium supplements), digoxin, lithium, methotrexate, biotin >30 microgram/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 autoimmune regulator (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 blood pressure (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 Visit 1 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 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

Related Information

Contact

Public contact
Name contact trial Clinical
Address Kyutaromachi 4-chome 1-3, Chuo-ku, Osaka city, Osaka Osaka Japan 541-0056
Telephone +81-6-4560-2001
E-mail ICONCR-Chiken@iconplc.com
Affiliation ICON Clinical Research GK
Scientific contact
Name Christopher Sibley
Address Tuborg Boulevard 12 2900 Hellerup, Denmark Japan 2900
Telephone 1-650-352-8389
E-mail CSY@ascendispharma.com
Affiliation Ascendis Pharma Bone Diseases A/S