Hypoparathyroidism (HP) in Adults MedDRA version: 20.0 Level: PT Classification code 10021041 Term: Hypoparathyroidism System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
Product Name: TransCon PTH low-dose pen
Product Code: TransCon PTH
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Teriparatide conjugated to a multiarm polyethylene
Sponsors
Ascendis Pharma Bone Diseases A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females aged =18 years 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 hypocalcemia in the setting of inappropriately low serum parathyroid hormone (PTH) levels. 3. On a stable dose* for at least 12 weeks prior to Screening of: - =0.25 µg BID of calcitriol (active vitamin D) or =0.5 µg BID or =1.0 µg daily of alfacalcidol (active vitamin D) and - =400 mg BID calcium citrate or carbonate If subject has a history of hypercalcemia on such doses, subject may be taking 30 mL/min/1.73m2 during Screening 8. Thyroid-stimulating hormone (TSH) within normal laboratory limits within the 12 weeks prior to Visit 1; if on suppressive therapy for thyroid cancer, TSH level must be =0.2 µIU/mL 9. If treated with thyroid hormone replacement therapy, the dose must be stable for at least 12 weeks prior to Visit 1 10. Able to perform daily subcutaneous self-injections of study drug (or have a designee perform injection) via a pre-filled injection pen 11. Written, signed, informed consent of the subject Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Known activating mutation in the calcium-sensing receptor (CaSR) gene 2. Impaired responsiveness to PTH (pseudohypoparathyroidism) which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia 3. Any disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than HP, such as active hyperthyroidism; Paget’s disease; hypomagnesemia; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus; severe and chronic cardiac, liver, or renal disease; Cushing syndrome; rheumatoid arthritis; multiple myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy (other than low-risk well differentiated thyroid cancer or basal cell skin cancer); parathyroid carcinoma within 5 years prior to Screening; acromegaly; multiple endocrine neoplasia types 1 and 2 4. Use of loop diuretics, phosphate binders (other than calcium carbonate/calcium citrate), digoxin, lithium, methotrexate, or systemic corticosteroids (other than replacement therapy) 5. Use of thiazide diuretic within 4 weeks prior to the Screening 24-hour urine collection or the first dose adjustment of SOC during Screening 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 12 weeks prior to Visit 1 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 Visit 1 8. Use of bisphosphonates (oral or IV) or denosumab within 2 years prior to Visit 1 9. Non-hypocalcemic seizure disorder with a history of a seizure within 26 weeks prior to Visit 1 NOTE: History of seizures that occur in the setting of hypocalcemia is not exclusionary 10. Increased risk for osteosarcoma, such as those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, open epiphyses, 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. NOTE: Highly effective contraception (see Appendix 7) is required for sexually active women of childbearing potential during the trial and for 2 weeks after the last dose of study drug, and pregnancy testing will be performed throughout the trial. Sexually active women of childbearing potential who are unwilling to use highly effective contraception are excluded from the trial. 12. Diagnosis of drug or alcohol dependence within 3 years prior to Visit 1 13. Disease processes that may adversely affect gastrointestinal absorption including but not limited to short bowel syndrome, bowel resection, gastric bypass, tropical sprue, active celiac disease, active ulcerative colitis, gastroparesis, AIRE gene mutations with malabsorption, and active Crohn’s disease 14. Chronic or severe cardiac disease within 26 weeks prior to Visit 1 including but not limited to congestive heart failure, myocardial infarction, QTcF >430 msec (males) or >450 msec (females), severe or uncontrolled arrhythmias, bradycardia (resting heart rate 150 mm Hg or diastolic >95 mm Hg) 15. Cerebrovascular accident within 5 y
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effectiveness of daily TransCon PTH on serum and urine calcium levels (FECa) and active vitamin D and calcium doses at 4 weeks of treatment.;Secondary Objective: - To assess the safety and tolerability of daily TransCon PTH - To assess the effectiveness of daily TransCon PTH on serum and urine calcium levels (FECa) and active vitamin D and calcium doses during the Extension Period - To assess the treatment effect of daily TransCon PTH on daily pill burden (vitamin D and calcium) - To assess the treatment effect of daily TransCon PTH on serum phosphate, serum magnesium, and calcium x phosphate product (sCa x sP product) - To assess the treatment effect of daily TransCon PTH on hypocalcemia and hypercalcemia symptoms, emergency room (ER) visits, and hospitalizations - To assess anti-PTH and anti-PEG antibody responses;Primary end point(s): Primary Efficacy Endpoints: At 4 weeks of treatment, the proportion of subjects with: -Albumin-adjusted sCa within the normal range, and -Spot AM FECa within normal range (=2%) or a reduction by at least 50% from baseline, and -Not taking active vitamin D supplements, and -Taking =1000 mg/day of calcium supplements;Timepoint(s) of evaluation of this end point: At 4 weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficay Endpoint: At 4 weeks of treatment, the proportion of subjects with: -Albumin-adjusted sCa within the normal range and -FECa within the normal range or a reduction by at least 50% from baseline and -Not taking active vitamin D supplements and -Taking =500 mg/day of calcium supplements Other Secondary Efficacy Endpoints: Primary and key secondary efficacy endpoints measured at predefined timepoints over the Extension Period. For the analysis of these endpoints in the Extension Period, the 24-hour urine calcium excretion will be used. At 4 weeks of treatment and at predefined timepoints over the Extension Period: -Calcium and vitamin D doses -Number of SOC supplements (pill burden) -Spot AM FECa -Serum phosphate -Serum magnesium -sCa x sP product, including proportion of subjects with sCa x sP product =55 mg2/dL2, =52 mg2/dL2, and =44 mg2/dL2 -Albumin-adjusted or ionized sCa At predefined timepoints over the Extension Period: -24-hour urine calcium excretion;Timepoint(s) of evaluation of this end point: At 4 weeks of treatment and predefined timepoints over the Extension Period. | — |
Countries
Canada, Denmark, Germany, Italy, Norway, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Ascendis Pharma A/S
Outcome results
None listed