Study of encaleret compared to standard care in patients with autosomal dominant hypocalcemia type 1

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What is this study about?

This clinical study is looking at a rare genetic condition called Autosomal Dominant Hypocalcemia Type 1, which is caused by changes in a specific gene that affects calcium levels in the body. People with this condition typically have low calcium levels in their blood and high calcium levels in their urine, which can cause various symptoms such as muscle cramps, muscle spasms, tingling sensations, headaches, kidney stones, and seizures. The study will test a medication called encaleret sulfate, also known by the code name CLTX-305, and compare it to standard of care treatment. Standard of care treatment may include medications such as calcium carbonate, calcium acetate, alfacalcidol, calcitriol, and colecalciferol, which are typically used to manage calcium levels in patients with this condition. The purpose of the study is to find out if encaleret is more effective than standard of care treatment in normalizing calcium levels in the blood and reducing calcium loss through urine.

Participants in this study will be randomly assigned to receive either encaleret or to continue with their standard of care treatment. The study is divided into several periods where treatment doses may be adjusted to find the best dose for each person. During the study, participants will have regular visits where doctors will check calcium levels in blood and urine, measure parathyroid hormone levels (a hormone that helps control calcium), and monitor other important body substances like phosphate and magnesium. Blood tests, urine tests, heart monitoring using electrocardiogram, kidney ultrasound examinations, and questionnaires about quality of life will be performed throughout the study. The study will last up to 54 months, and participants will be closely monitored for any side effects or changes in their condition.

The main goal is to determine how many participants achieve normal calcium levels in their blood and reduced calcium levels in their urine with each treatment approach. The study will also look at whether parathyroid hormone levels improve, how participants feel in their daily lives using health surveys, changes in kidney health, and the overall safety of the treatments. Doctors will track any unwanted effects, changes in vital signs, and the need for additional calcium or vitamin D supplements during the study. For those receiving encaleret, blood samples will be taken to measure medication levels in the body to ensure the drug is working properly.

1 Standard of care optimization period

This phase involves optimizing your current treatment before starting the main study period. The goal is to adjust your medications to achieve the best possible control of your calcium levels.

Your doctor will adjust doses of calcium supplements and active vitamin D (such as alfacalcidol, calcitriol, or colecalciferol) taken by mouth. The specific doses will be determined based on your individual needs.

If you are taking thiazide diuretics (water pills sometimes used for blood pressure), you will need to stop taking them at least 14 days before this period begins and remain off them through week 24 of the study. Your doctor will prescribe alternative blood pressure medication if needed.

If you are taking phosphate binders (medications that help control phosphate levels) other than calcium salts, you will need to stop them at least one day before this period begins.

If you are taking magnesium or potassium supplements, you will need to stop these before receiving the first dose of encaleret.

If you are taking potassium-sparing diuretics (a specific type of water pill), you will need to stop these before receiving the first dose of encaleret.

During this period, your doctor will monitor your albumin-corrected blood calcium (a measure of calcium in your blood adjusted for protein levels) and your 24-hour urinary calcium (the amount of calcium you excrete in urine over a full day).

2 Random assignment to treatment group

After the optimization period, you will be randomly assigned to one of two treatment groups. This is similar to flipping a coin to decide which treatment you receive.

One group will receive encaleret tablets taken by mouth.

The other group will continue with standard of care treatment, which consists of calcium supplements (such as calcium carbonate or calcium acetate) and active vitamin D medications (such as alfacalcidol, calcitriol, or colecalciferol) taken by mouth.

Both you and your doctor will know which treatment group you are assigned to, as this is an open-label study.

3 First maintenance period

You will begin taking your assigned treatment according to the group you were placed in.

If you are in the encaleret group, you will take encaleret tablets by mouth. Your doctor will determine the appropriate dose and frequency for you. The dose may be adjusted during this period to achieve optimal calcium levels.

If you are in the standard of care group, you will continue taking calcium supplements and active vitamin D medications by mouth. Your doctor will adjust the doses as needed.

During this period, your doctor will monitor various blood and urine measurements, including albumin-corrected blood calcium, 24-hour urinary calcium excretion, intact parathyroid hormone (a hormone that helps regulate calcium levels), blood phosphate, and blood magnesium.

You will also have electrocardiograms (tests that measure the electrical activity of your heart) to monitor your heart function.

Your vital signs and physical condition will be regularly assessed.

4 Treatment adjustment period

This period allows for fine-tuning of your treatment doses based on how you responded during the first maintenance period.

If you are taking encaleret, your doctor may adjust the dose to better control your calcium levels. Blood levels of encaleret will be measured to ensure the medication has reached a steady concentration in your body.

If you are on standard of care treatment, your doctor may adjust the doses of calcium supplements and active vitamin D medications.

Monitoring of blood and urine measurements will continue throughout this period.

5 Second maintenance period through week 24

You will continue taking your assigned treatment at the optimized dose determined during the adjustment period.

This period extends through week 24 of the study and serves to evaluate the long-term effectiveness and safety of your treatment.

Your doctor will continue to monitor albumin-corrected blood calcium, 24-hour urinary calcium excretion, intact parathyroid hormone, blood phosphate, and blood magnesium levels.

Additional measurements will include urine levels of magnesium, phosphate, sodium, and citrate to assess how your kidneys are handling these substances.

You will complete questionnaires about your quality of life and how you are feeling physically and mentally using the 36-Item Short Form Health Survey.

Your doctor will perform renal ultrasound examinations (imaging tests of your kidneys) to check for nephrocalcinosis (calcium deposits in the kidneys) and nephrolithiasis (kidney stones).

Regular safety assessments will include monitoring for any side effects, changes in vital signs, physical examinations, electrocardiograms, and laboratory tests of your blood and urine.

If you are in the encaleret group, the amount and frequency of any additional calcium supplements or active vitamin D you may need will be recorded. You should not take more than 600 milligrams per day of oral calcium during this period.

Blood levels of encaleret will be measured again during this period to confirm steady medication levels.

Who Can Join the Study?

You must be at least 18 years old at the time of signing the informed consent form
You must have a confirmed genetic change in the CASR gene, which is the gene responsible for your condition. This can be shown through a genetic test report. If you do not have this documentation, you must be willing to have genetic testing done. If you have had a bone marrow transplant, the genetic test must have been done before the transplant. If you have had a blood transfusion, you must wait 2 weeks after receiving packed red blood cells or 4 weeks after receiving whole blood before having the genetic test
You must have a documented history of symptoms or signs related to your condition. Symptoms may include feeling anxious or agitated, back pain, difficulty thinking clearly, muscle cramps or spasms, muscle tightness or twitching, muscle pain or stiffness, headaches, tingling sensations, numbness, tremor, spasms in various parts of the body, passing large amounts of urine, excessive thirst, kidney stones, seizures, or throat tightness. Signs may include calcium deposits in the brain, nephrocalcinosis (calcium deposits in the kidneys), too much calcium in the urine, early cataracts, changes on heart rhythm tests, or specific physical examination findings
If you are taking thiazide diuretics (water pills used to remove excess fluid), you must stop taking them at least 14 days before a specific study visit and continue without them through Week 24 of the study. If you take these for high blood pressure, your doctor will prescribe a different medicine
If you are taking phosphate binders (medicines that help control phosphate levels), except calcium salts, you must stop taking them at least one day before a specific study visit
If you are taking magnesium or potassium supplements, you must be willing to stop taking them before receiving the first dose of the study medicine
If you are taking potassium-sparing diuretics (a type of water pill that helps keep potassium in your body), you must be willing to stop taking them before receiving the first dose of the study medicine
You must meet specific requirements for optimizing your standard care treatment as defined by the study
If you are a man with a female partner who can become pregnant, you must use acceptable birth control methods as defined by the study
If you are a woman who has gone through menopause (no menstrual period for 12 months confirmed by a blood test) or have had surgery to remove your ovaries or uterus, you may participate without using birth control
If you are a woman who can become pregnant, you must use highly effective birth control methods starting at the screening visit and for 3 months after your last dose of the study medicine
You must be able to provide signed informed consent, which means you understand and agree to follow the study requirements and restrictions

Who Cannot Join the Study?

The source data does not provide specific exclusion criteria for this clinical trial
This means there is no available information about which patients cannot participate in the study
If you are interested in participating, you would need to contact the study team directly to learn about any conditions or situations that would prevent participation

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

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Other Sites

Site Name	City	Country
Ospedale San Raffaele S.r.l.	Milan	Italy
Hospices Civils De Lyon	Lyon	France
Universita’ Campus Bio-medico Di Roma	Rome	Italy
Vseobecna Fakultni Nemocnice V Praze	Prague	Czechia
Region Midtjylland	Aarhus	Denmark
Vrije Universiteit Brussel	Jette	Belgium
Bicetre Hospital	Le Kremlin-Bicetre	France
Azienda Ospedaliero Universitaria Pisana	Pisa	Italy
Enezfmr Uwrtyqgbmxnt Mympqwg Chkxery Rkyjxaacn (acpsgka Mks	Rotterdam	The Netherlands

Trial status

Country	Status	Recruitment Start
Belgium	ended	30.07.2023
Czechia	Not recruiting	30.07.2023
Denmark	Not recruiting	30.07.2023
France	Not recruiting	30.07.2023
Italy	Not recruiting	30.07.2023
The Netherlands	Not recruiting	30.07.2023

Trial locations

Investigated drugs:

Encaleret is an investigational medication being studied in this clinical trial. It is being tested as a potential treatment for people with autosomal dominant hypocalcemia type 1, a rare genetic condition that causes low calcium levels in the blood. The study will compare how well encaleret works against the usual treatments that doctors currently use for this condition. The main goal is to see if encaleret can help improve calcium levels in the blood and reduce the amount of calcium lost through urine.

Standard of Care refers to the current usual treatments that doctors typically prescribe for people with autosomal dominant hypocalcemia type 1. These are the established treatments that are commonly used to manage low calcium levels in patients with this condition. In this study, standard of care will be compared with the investigational medication to see which approach works better for managing the condition.

Autosomal Dominant Hypocalcemia Type 1 – This is a rare genetic disorder that affects calcium regulation in the body. The condition is inherited in an autosomal dominant pattern, meaning a person needs only one copy of the altered gene to develop the disorder. People with this disease have abnormally low levels of calcium in their blood, even though their parathyroid glands are functioning. The disorder also causes excessive calcium to be lost through the urine. This happens because the calcium-sensing receptors in the body are overly sensitive, leading the body to incorrectly regulate calcium levels. The condition can also affect levels of other minerals in the blood, including magnesium and phosphate.

Trial ID:

2022-501398-38-00

Protocol code:

CLTX-305-302

NCT ID:

NCT05680818

Trial Phase:

Therapeutic confirmatory (Phase III)

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Study of encaleret compared to standard care in patients with autosomal dominant hypocalcemia type 1

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?