Clinical trial NCT06547151: Evaluating the Safety and Efficacy of AMOR-1 as a Treatment for Hypocalcemia Associated With Hypoparathyroidism in Adults
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hypoparathyroidism
Keywords: Amorphous Calcium Carbonate
hypoparathyroidism
Hypopara
Hypocalcemia
Calcium Carbonate
Lead sponsor: Amorphical Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-09
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: AMOR-1 contains Amorphous Calcium Carbonate (ACC) nanoparticles, which provide higher calcium absorption and bioavailability compared to the crystalline form. Therefore, significantly smaller doses of elemental calcium provided by ACC may be sufficient to maintain the desired serum calcium levels in people with hypoparathyroidism. The lower calcium doses can potentially reduce the adverse effects, associated with long-term, high daily doses of calcium supplementation, consumed by these patients.

The main question for the study is: Can replacing the current calcium supplement with AMOR-1, which contains half the amount of elemental calcium, maintain blood calcium levels in people with hypoparathyroidism? Patients with a history of hypoparathyroidism will be randomized in a 2:1 ratio to receive either AMOR-1 or Control (the conventional crystalline calcium carbonate supplement), respectively. Their current dose of calcium supplement will be gradually replaced with AMOR-1 or the Control over 2-4 weeks. At the end of the replacement phase, participants in the AMOR-1 arm are anticipated to receive 50% of the elemental calcium compared to their initial intake from the crystalline calcium supplements. Subjects in the Control arm will maintain their initial elemental calcium intake. Following this replacement phase, the participants will continue receiving their individual dose of AMOR-1 or the Control for an additional 10-12 weeks (Dose Maintenance phase). At the end of this phase, the participants will revert to their initial calcium supplement and will be monitored for an additional month until the end of the study. All participants will receive an active form of vitamin D in parallel to the study treatment. Throughout the study, participants will be routinely monitored for safety and efficacy, including calcium levels in the blood and urine.

Eligibility criteria: Inclusion Criteria:

1. An understanding, ability, and willingness to fully comply with study procedures and restrictions.
2. Ability to voluntarily provide written, signed, and dated informed consent as applicable to participants in the study.
3. Adult males or females 18 or older (prior to screening). Those \< 25 years old will be examined radiologically to ensure epiphyseal closure prior to enrollment into the study.
4. Hypoparathyroidism patients, from any etiology, who are on currently available Standard of Care (SoC) e.g., calcium supplement and active vitamin D metabolite/analog.
5. Oral calcium ≥ 1000 mg QD above the normal dietary calcium intake
6. 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.
7. Vitamin D metabolite/analog therapy with calcitriol ≥0.25μg QD or alfacalcidol ≥0.50 μg QD.
8. Serum 25-hydroxyvitamin D (25OHD) ≥50 nmol/l (20 ng/ml), or if below, considered not clinically significant by the Investigator.
9. No change of treatment for hypocalcemia over the last 3 months prior to Screening as reported by the patient or through medical documentation.
10. Absence of symptoms from hypocalcemia over the last 3 months prior to Screening as reported by the patient or through medical documentation.
11. 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.
12. 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 Criteria:

1. Any disease that might affect calcium metabolism or calcium- 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, severe and chronic cardiac, liver or renal disease, , acute pancreatitis, malnutrition, recent prolonged immobility, active malignancy, myeloma.
2. Hepatic transaminases (ALT and AST) \> 3 times the upper limit.
3. Severe renal insufficiency defined as estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73 m2.
4. Clinical history of symptomatic renal stones within the past 3 months. Subjects with asymptomatic renal stones are permitted.
5. Poorly controlled short bowel syndrome, bowel resection, tropical sprue, celiac disease, ulcerative colitis, and Crohn's disease.
6. Chronic/severe cardiac disease including but not limited to cardiac failure, arrhythmias, bradycardia (resting heart rate \< 48 beats/minute).
7. Seizure disorder/epilepsy with a history of a seizure within the previous 6 months prior to screening.
8. Acute gout within 6 months prior to screening.
9. Cerebrovascular accident within 2 years prior to Screening.
10. Subjects dependent on regular parenteral calcium infusions (e.g., calcium gluconate) to maintain calcium homeostasis.
11. 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 (3 months), or systemic corticosteroids (3 months).
12. 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.
13. Other drugs known to influence calcium and bone metabolism, such as calcitonin, cinacalcet hydrochloride, and fluoride tablets within 3 months prior to screening.
14. Use of oral bisphosphonates within 6 months or IV bisphosphonate preparations within 12 months prior to screening.
15. Previous treatment with PTH/parathyroid hormone-related protein-like drugs, including PTH(1-84) and PTH(1-34) within 30 days prior to screening.
16. History of diagnosed substance abuse or alcohol dependence within the previous 3 years.
17. Pregnant/ breastfeeding patients.

Primary outcomes:
measure: Percentage of Subjects Who Achieved the Primary Composite Endpoint at Week 14
timeFrame: 14 weeks
Secondary outcomes:
measure: Albumin-adjusted serum calcium
timeFrame: Week 4 to Week 14
measure: Urinary Calcium Excretion
timeFrame: Week 14
measure: Urine calcium excretion above 300mg/24h
timeFrame: Week 4 to Week 14
measure: GI symptoms
timeFrame: Week 4 to Week 14
measure: Symptoms associated with hypocalcemia
timeFrame: Week 4 to Week 14
measure: Hypoparathyroidism Patient Experience Scale (HPES)- Experience (HPES) - Symptom
timeFrame: Week 14
measure: HPES - Impact
timeFrame: Week 14
measure: HPES - Symptom - Physical Domain
timeFrame: Week 14
measure: HPES - Symptom - Cognitive Domain
timeFrame: Week 14
measure: HPES - Impact - Physical Functioning Domain
timeFrame: eek 14
measure: HPES - Impact - Daily Life Domain
timeFrame: Week 14
measure: HPES - Impact - Psychological Well-Being Domain
timeFrame: Week 14
measure: HPES - Impact - Social Life and Relationships Domain
timeFrame: Week 14
measure: 36-item Short Form (SF-36) survey
timeFrame: Week 14
Other outcomes:
Locations:
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center
city: Petah tikva
country: Israel
facility: Rabin Medical Center, Belinson Campus
city: Rehovot
country: Israel
facility: Kaplan Medical Center
Study officials:
affiliation: Principal Investigator
name: Ilan Shimon, MD
role: PRINCIPAL_INVESTIGATOR
References: