PaTH Forward: a study to investigate the safety and efficacy of TransCon PTH administered as an injection under the skin daily in adults with hypoparathyroidism.
- Conditions
- Hypoparathyroidism (HP) in AdultsMedDRA version: 20.0Level: PTClassification code 10021041Term: HypoparathyroidismSystem Organ Class: 10014698 - Endocrine disordersTherapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2018-004815-33-IT
- Lead Sponsor
- Ascendis Pharma Bone Disease A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 40
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 <0.25 µg BID of calcitriol, <0.5 µg BID or <1.0 µg daily of alfacalcidol, or <400 mg BID of calcium citrate or carbonate, with approval of Medical Monitor/Medical Expert
*Does not preclude occasional (<3/week) rescue doses of active vitamin D and/or calcium for symptomatic hypocalcemia
4.Optimization of supplements prior to randomization to achieve the target levels of:
•25(OH) vitamin D levels of 30-70 ng/mL (75-175 pmol/mL) and
•Magnesium level within the normal range* and
•Albumin-adjusted or ionized serum calcium (sCa) level in the lower half of the normal range
* If subject has a history of inability to be successfully
managed within the normal range for magnesium level, a level slightly below the normal range is acceptable with approval of the Medical Monitor/Medical Expert
5.BMI 17-40 kg/m2 at Visit 1
6.If =25 years of age, radiological evidence of epiphyseal closure based on x-ray of non-dominant wrist and hand
7.eGFR >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
Known activating mutation in the calcium-sensing receptor (CaSR) geneImpaired responsiveness to PTH (pseudohypoparathyroidism) which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemiaAny disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than HP Use of loop diuretics, phosphate binders (other than calcium carbonate/calcium citrate), digoxin, lithium, methotrexate, or systemic corticosteroids (other than replacement therapy)Use of thiazide diuretic within 4 weeks prior to the Screening 24-hour urine collection or the first dose adjustment of SOC during ScreeningUse 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 1Use 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 1Use of bisphosphonates (oral or IV) or denosumab within 2 years prior to Visit 1Non-hypocalcemic seizure disorder with a history of a seizure within 26 weeks prior to Visit 1Increased 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 skeletonPregnant or lactating women.Diagnosis of drug or alcohol dependence within 3 years prior to Visit 1 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 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 <50 beats/minute), symptomatic hypotension, systolic BP <80 mm Hg or diastolic <40 mm Hg, or poorly controlled hypertension (systolic BP >150 mm Hg or diastolic >95 mm Hg) Cerebrovascular accident within 5 years prior to Visit 1 History of renal colic or acute gout within 52 weeks prior to Visit 1 Any disease or condition that, in the opinion of the investigator, may 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 1-year duration of the trial Known allergy or sensitivity to PTH or any of the excipients [metacresol, mannitol, succinic acid, NaOH/(HCl)] Participation in another clinical trial in which receipt of investigational drug or device occurred within 8 weeks (or at least 5.5 times the half-life of the investigational drug) prior to Visit 1
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method