RecruitingPhase 2NCT06547151

Evaluating the Safety and Efficacy of AMOR-1 as a Treatment for Hypocalcemia Associated With Hypoparathyroidism in Adults

A Phase 2, Prospective, Multinational, Multicenter, Double-Blind, Randomized Study to Evaluate the Safety and Efficacy of AMOR-1 as a Treatment of Hypocalcemia Associated With Hypoparathyroidism by Replacement of Currently Used Calcium Supplements (CS) in Adults.

Sponsor

Amorphical Ltd.

Enrollment

81 participants

Start Date

Dec 15, 2024

Study Type

INTERVENTIONAL

Conditions

Hypoparathyroidism

Summary

This clinical trial aims to evaluate the efficacy and safety of AMOR-1, consisting of Amorphous Calcium Carbonate (ACC) as the active drug substance, in treating hypocalcemia in adults with hypoparathyroidism.

Eligibility

Min Age: 18 Years

Inclusion Criteria12

An understanding, ability, and willingness to fully comply with study procedures and restrictions.
Ability to voluntarily provide written, signed, and dated informed consent as applicable to participants in the study.
Adult males or females 18 or older (prior to screening). Those \< 25 years old will be examined radiologically (Bone age X-ray of non-dominant wrist and hand) to ensure epiphyseal closure prior to enrollment into the study.
Hypoparathyroidism patients, from any etiology, who are on currently available Standard of Care (SoC) e.g., calcium supplement and active vitamin D metabolite/analog.
Oral calcium ≥ 1000 mg QD above the normal dietary calcium intake
Albumin-adjusted total serum calcium concentration level between 7.5 mg/dL and 10.5 mg/dL, or if outside of this range, considered not clinically significant by the Investigator.
Vitamin D metabolite/analog therapy with calcitriol ≥0.25μg QD or alfacalcidol ≥0.50 μg QD.
Serum 25-hydroxyvitamin D (25OHD) ≥50 nmol/l (20 ng/ml), or if below, considered not clinically significant by the Investigator.
No change of treatment for hypocalcemia over the last 3 months prior to Screening as reported by the patient or through medical documentation, or if a change has occurred, it is expected to remain stable, as determined by the Investigator.
Absence or stable symptoms from hypocalcemia over the last 3 months prior to Screening as reported by the patient or through medical documentation.
For subjects receiving thyroid replacement therapy, the dose is stable for at least 6 weeks prior to screening and the TSH serum levels are within the normal range. A serum TSH level below the lower limit of the normal range but not undetectable in participant treated with thyroid hormone may be allowed if there is no anticipated need for a change in thyroid hormone dose during the trial.
Female subjects who are postmenopausal (12 consecutive months of spontaneous amenorrhea and age \>= 51 years), or who are surgically sterilized may be enrolled, as may women of childbearing potential who had a negative pregnancy test at screening and are willing to use two medically acceptable methods of contraception for the duration of the study and undergo pregnancy testing according to the study protocol.

Exclusion Criteria19

Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, such as active hyperthyroidism, Paget's disease of bone, Type 1 or poorly controlled Type 2 diabetes mellitus (HbA1c \> 9%), acromegaly, multiple endocrine neoplasia types I and II, Cushing's syndrome or disease, acute pancreatitis, malnutrition, recent prolonged immobility.
Severe liver disease (Child-Pugh score \>9) (US FDA, 2003) or hepatic transaminases (ALT and AST) \> 3 times the upper limit.
Severe renal insufficiency defined as estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73 m2.
Clinical history of symptomatic renal stones within the past 3 months. Subjects with asymptomatic renal stones are permitted.
Poorly controlled short bowel syndrome, bowel resection, tropical sprue, celiac disease, ulcerative colitis, and Crohn's disease.
Chronic or severe cardiac disease within the past 6 months including but not limited to heart failure classified as NYHA Class II-IV (Dolgin and NYHA, 1994), uncontrolled arrhythmias, bradycardia (resting heart rate \< 48 beats/minute), QTc \>450msec (males) or \>470 msec (females) on ECG.
History of active or untreated malignancy (excluding thyroid cancer or basal cell skin cancer) within the past 2 years. For thyroid cancers, low-risk well-differentiated thyroid cancer that is stable does not require a disease-free period. High-risk thyroid cancer or uncontrolled cases must be disease-free for at least 1 year prior to Screening.
Seizure disorder/epilepsy with a history of a seizure within the previous 6 months prior to screening.
Acute gout within 6 months prior to screening.
Cerebrovascular accident within 6 months prior to Screening.
Subjects dependent on regular parenteral calcium infusions (e.g., calcium gluconate) to maintain calcium homeostasis.
Use of prohibited medications within respective prohibited periods prior to screening such as loop diuretics (30 days), raloxifene hydrochloride (3 months), lithium (30 days), methotrexate at dose \>20 mg per week, or systemic corticosteroids (3 months).
Thiazide diuretics may be permitted if the dosage has remained stable for three months prior to screening, and there is no expected need for a dosage change during the trial.
Other drugs known to influence calcium and bone metabolism, such as calcitonin, cinacalcet hydrochloride, and fluoride tablets within 3 months prior to screening.
Use of oral bisphosphonates within 6 months or IV bisphosphonate preparations within 12 months prior to screening.
Previous treatment with PTH/parathyroid hormone-related protein-like drugs, including PTH(1-84) and PTH(1-34) within 30 days prior to screening.
Current use of Amorphous Calcium Carbonate (ACC) food supplement.
History of diagnosed substance abuse or alcohol dependence within the previous 3 years.
Pregnant/ breastfeeding patients.