A Phase 3, Multicenter, Randomized, Open-Label Trial Investigating the Safety, Tolerability and Efficacy of Palopegteriparatide Administered Subcutaneously Daily at Doses Greater Than 30 μg/Day in Adult Participants With Hypoparathyroidism
This trial has a duration of 78 weeks and will include adult participants already on treatment with palopegteriparatide at doses at or greater than 30 mcg/day. All participants will receive subcutaneous palopegteriparatide during the trial and will be individually and progressively titrated to an optimal dose at pre-specified dose levels. The primary purpose of the trial is to provide additional evidence of treatment effect and safety of palopegteriparatide at doses greater than 30 mcg/day in adults with hypoparathyroidism. The trial will be conducted in the US.
⁃ Males and females, ≥18 years of age at the time of providing informed consent
⁃ Participants with postsurgical chronic hypoparathyroidism (HP), or auto-immune, genetic, or idiopathic HP, for at least 26 weeks
⁃ Receiving doses of palopegteriparatide at or above 30 µg/day
⁃ For individuals receiving 30 µg/day: evidence that dose is insufficient to keep serum calcium in the normal range, defined as:
⁃ Documented hypocalcemia within 12 weeks prior to Screening; and/or Standing dose of calcitriol ≥0.25 μg/day, and / or (elemental) calcium ≥1500 mg/day (e.g., calcium citrate, calcium carbonate etc.) for at least 4 weeks prior to Screening
⁃ For individuals receiving 33 µg/day or greater: no requirement for documented hypocalcemia or minimum doses of calcitriol or elemental calcium
⁃ Confirmation of laboratory parameters (Central and Local) within 2 weeks of screening visit and prior to randomization:
‣ 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 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 (1.10 - 1.32 mmol/L)
• 5\. BMI 17- 40 kg/m2 at Screening
• 6\. If ≤25 years of age, radiological evidence of epiphyseal closure based on locally interpreted X-ray of non-dominant wrist and hand
• 7\. eGFR ≥30 mL/min/1.73 m2 during Screening using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula