2022-503126-12-00撤回3 期
A phase 3 multicenter, randomized, placebo-controlled, double‑blind study to evaluate the efficacy and safety of eneboparatide (AZP‑3601), a parathyroid hormone receptor agonist, in patients with chronic hypoparathyroidism (CALYPSO)
适应症
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 入组人数
- 12
- 试验地点
- 5
- 主要终点
- (MT)-Efficacy: After 24 weeks of treatment, the proportion of patients in the eneboparatide treatment group vs. placebo: •Achieving complete independence from active vitamin D; •Achieving independence from therapeutic doses of oral calcium (i.e., taking oral elemental calcium supplements ≤600 mg/day); and •With albumin-adjusted serum calcium within the normal range (8.3 to 10.6 mg/dL).
研究概览
简要总结
Main Treatment (MT) period: Primary efficacy objective: To demonstrate the efficacy of a daily treatment with eneboparatide for 24 weeks compared to placebo on therapeutic doses of active vitamin D and oral calcium, and on serum calcium levels.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •(MT) Male or female patients, aged 18 to 80 years, inclusive at screening;
- •(MT) Patient able to perform daily SC self-injections of study treatment in the abdomen (or have a designee perform the injection) using a pre filled injection pen;
- •(MT) a) Female patients may be of non-childbearing potential (i.e. post menopausal [absence of menstrual bleeding for 1 year prior to screening, without any other medical reason], hysterectomy or bilateral oophorectomy), or of childbearing potential. Women of childbearing potential (WOCBP) must agree to a true abstinence (when in line with the preferred and usual lifestyle of the patient) or to use an highly effective method of contraception throughout the study and for 30 days after the end of the treatment. b) For male patients: their WOCBP partner must agree to use a highly effective method of contraception;
- •(MT) Negative pregnancy test at screening and at Day 1 visit for WOCBP;
- •(MT) Willing and able to sign the Informed Consent Form and to comply with the requirements of the study protocol.
- •(MT) Patients with cHP for at least 12 months at screening, documented on medical records
- •(MT) Prior to start of study treatment, two paired serum calcium/serum parathyroid hormone (PTH) values, showing low PTH levels (<20 pg/mL), and albumin adjusted serum calcium or ionized serum calcium either: a) Below the lower limit of normal (LLN) value of the laboratory; or b) Within the normal range of the laboratory under standard of care. Note: At least one of the two paired serum calcium/serum PTH values should have been measured within the last 12 months preceding start of treatment;
- •(MT) Requirement for therapy with calcitriol ≥0.5 μg per day or alphacalcidol ≥1 μg per day, and requirement for supplemental oral (elemental) calcium treatment ≥1000 mg per day over and above patient’s dietary calcium intake at Day 1 visit;
- •(MT) Successful completion of the Optimization period based on two consecutive measurements of albumin-adjusted serum calcium at least 1 week apart within the range of 7.8 to 9.0 mg/dL and with no more than 25% of change in the daily dose of any of active vitamin D and oral calcium supplements between the two measurements;
- •(MT) Either of the following: a) If on suppressive therapy for thyroid cancer, serum thyroid stimulating hormone (TSH) level should be >0.2 µIU/mL at screening and the dose of thyroid medication should be stable for at least 6 weeks prior to start of treatment; b) In other cases, serum TSH should be within the LLN and 1.5 fold upper limit of normal (ULN) at screening;
- •(MT) Serum magnesium levels within laboratory normal limits prior to start of treatment;
- •(MT) Serum 25hydroxy vitamin D level >30ng/mL and <70ng/mL (75 to 175nmol/L) prior to start of treatment;
- •(MT) Estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration formula) ≥30 mL/minute/1.73 m² on two separate measurements with at least one recent value (i.e. at Screening visit or during the Optimization period);
排除标准
- •(MT) Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation;
- •(MT) History of cerebrovascular accident within 6 months prior to screening;
- •(MT) Patients with active uncontrolled malignancy over the past 2 years at the time of screening;
- •(MT) Patients with a history of any other cancer than thyroid cancer (except basal cell skin cancer or squamous cell skin cancer) who have not been disease-free for a period of at least 2 years at the time of screening;
- •(MT) Acute gout <2 months prior to screening;
- •(MT) Patients dependent on parenteral calcium infusions (e.g. calcium gluconate) to maintain calcium homeostasis;
- •(MT) Use of medications such as loop and thiazide diuretics, raloxifene hydrochloride, lithium, methotrexate, cardiac glycosides (e.g. digoxin or digitoxin) or systemic corticosteroids within 4 weeks prior to start of treatment;
- •(MT) Previous treatment with PTH/parathyroid hormone-related protein-like drugs, including PTH(1-84) and PTH(1-34) within 3 months prior to screening;
- •(MT) Use of Other drugs known to influence calcium and bone metabolism within 4 weeks prior to screening;
- •(MT) Use of oral bisphosphonates within 6 months prior to screening or intravenous bisphosphonate preparations within 12 months prior to screening;
- •(MT) Use of denosumab within 18 months prior to screening;
- •(MT) Clinically significant abnormal values at screening for hematology, clinical chemistry, coagulation or urinalysis, as judged by the Investigator;
- •(MT) Seizure disorder/epilepsy with a history of a seizure within 6 months prior to screening;
- •(MT) History of symptomatic urinary tract calculi within 3 months prior to screening;
- •(MT) Irradiation to the skeleton within 2 years prior to screening;
- •(MT) Pregnant or breastfeeding female patients;
- •(MT) Participation in any other interventional study in which the patient received an investigational drug or device study within 2 months (or within 5 times the half-life of the investigational drug [whichever comes first]) prior to screening;
- •(MT) Any disease or condition that, in the opinion of the Investigator, may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the study treatment or procedures, including treated malignancies that are likely to recur within the approximate duration of the study;
- •(MT) Any other reason that in the opinion of the Investigator would prevent the patient from completing participation or following the study schedule;
- •(MT) Known allergy or sensitivity to PTH, ingredients in the study treatment (eneboparatide or placebo), oral calcium supplements, or vitamin D supplements.
- •(MT) Abnormal arterial pressure at the time of screening, defined here as either: a) Symptomatic hypotension or systolic blood pressure (SBP) <100 mmHg; or b) SBP >150 mmHg and/or diastolic blood pressure (DBP) >100 mmHg;
- •(MT) Heart rate at rest outside the range of 50 to 100 beats/minute at screening;
- •(MT) Clinically significant abnormal standard 12-lead electrocardiogram (ECG, after resting for at least 5 minutes in supine position) indicative of severe cardiac disease, at screening, as judged by the Investigator;
- •(MT) Known history of autosomal-dominant hypocalcemia (resulting from gainoffunction calcium-sensing receptor or guanine nucleotide binding protein, alpha-11 mutations) or known pseudohypoparathyroidism (impaired responsiveness to PTH);
- •(MT) Any current disease that might affect calcium metabolism, calcium phosphate homeostasis or PTH levels, other than hypoparathyroidism;
- •(MT) Patients with increased risk for osteosarcoma;
- •(MT) Current uncontrolled active disease processes that may adversely affect gastrointestinal absorption;
结局指标
主要结局
(MT)-Efficacy: After 24 weeks of treatment, the proportion of patients in the eneboparatide treatment group vs. placebo: •Achieving complete independence from active vitamin D; •Achieving independence from therapeutic doses of oral calcium (i.e., taking oral elemental calcium supplements ≤600 mg/day); and •With albumin-adjusted serum calcium within the normal range (8.3 to 10.6 mg/dL).
(MT)-Efficacy: After 24 weeks of treatment, the proportion of patients in the eneboparatide treatment group vs. placebo: •Achieving complete independence from active vitamin D; •Achieving independence from therapeutic doses of oral calcium (i.e., taking oral elemental calcium supplements ≤600 mg/day); and •With albumin-adjusted serum calcium within the normal range (8.3 to 10.6 mg/dL).
次要结局
- (MT)-Key secondary efficacy endpoint 3 - At week 24, change from baseline in patient’s symptoms, as assessed by the average weekly HPT DD-SE cognitive domain score in the eneboparatide treatment group vs. placebo;
- (MT)-Key secondary efficacy endpoint 1 - At week 24, the proportion of patients in the eneboparatide treatment group vs. placebo who had hypercalciuria at baseline and normalize their 24 hour urinary calcium excretion level (i.e. achieve <250 mg/24 hours for females or <300 mg/24 hours for males);
- (MT)-Key secondary efficacy endpoint 2 - At week 24, change from baseline in patient’s symptoms, as assessed by the average weekly HPT DD-SE physical domain score in the eneboparatide treatment group vs. placebo;
- (MT)-Key secondary efficacy endpoint 4 - At week 24, change from baseline in the HPT-LIQ Physical Functioning domain score, in the eneboparatide treatment group vs. placebo;
- (MT)-Key secondary efficacy endpoint 5 - At week 24, change from baseline in the SF-36 Physical Functioning subscore in the eneboparatide treatment group vs. placebo.
- (MT)-Additional secondary endpoint at Week 24: The proportion of patients meeting each component during the fixed dose period: o Independence from active vitamin D; o Independence from therapeutic doses of oral calcium (i.e. taking oral elemental calcium supplements ≤600 mg/day); o Albumin-adjusted serum calcium within the normal range (8.3 to 10.6 mg/dL).
- (MT)-Additional secondary endpoint: Change from baseline in urinary calcium (24-hour collection) at Week 24
- (MT)-Additional secondary endpoint: Change from baseline in urinary calcium (24-hour collection) at Week 24 for patients who had hypercalciuria at baseline
研究者
Regulatory Submissions
Scientific
Amolyt Pharma
研究点 (5)
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