Not recruitingRare disease

Study on Immunosuppressive Therapies with Asfotase Alfa for Patients with Hypophosphatasia Experiencing Reduced Treatment Effectiveness

Verified siteRegistered drugNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying a rare condition called Hypophosphatasia, which affects the development of bones and teeth. The study aims to explore the use of certain treatments to help patients who have developed an immune response that reduces the effectiveness of their current treatment with Asfotase Alfa, a medication used to manage this condition. The trial will involve the use of immunosuppressive therapies, which are treatments that help reduce the activity of the immune system, to see if they can help restore the effectiveness of Asfotase Alfa.

Participants in the study will receive treatments over a period of time, and their response to the therapies will be monitored. The study will include medications such as Rituximab, Bortezomib, and Methotrexate Disodium, which are known to help manage immune responses. Some participants may also receive a placebo, which is a substance with no active medication, to compare the effects of the treatments. The study will track changes in the participants' condition and any side effects they may experience.

The purpose of this study is to evaluate whether these immunosuppressive therapies can help patients who have lost the therapeutic benefits of Asfotase Alfa due to an immune response. The trial will last for a set period, during which participants will undergo regular assessments to monitor their health and the effectiveness of the treatments. The goal is to find a way to improve the management of Hypophosphatasia for those affected by this immune-mediated loss of response.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Joining the study
Upon joining the study, participants will be informed about the trial's purpose, procedures, and potential risks and benefits. Participants or their legal guardians will be required to sign an informed consent or assent form, indicating their understanding and agreement to participate.
Step 2
Initial assessment
Participants will undergo an initial assessment to confirm eligibility. This includes checking for the presence of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs), as well as evaluating the severity of rickets using the Rickets Severity Score (RSS).
Step 3
Treatment phase
Participants will receive asfotase alfa treatment, administered subcutaneously (under the skin). The frequency and dosage will be determined by the study protocol and the participant's specific needs.
In addition to asfotase alfa, participants may receive immunosuppressive therapies (IST) to help reduce immune responses that may affect the treatment's effectiveness. These therapies may include medications such as rituximab, bortezomib, and methotrexate disodium, administered either intravenously (through a vein) or orally (by mouth).
Step 4
Monitoring and follow-up
Participants will be monitored regularly throughout the study. This includes blood tests to measure antibody levels and enzyme activity, as well as physical examinations and imaging tests to assess the improvement of rickets.
The study will track the number and percentage of participants who achieve a complete response to IST by Week 100, defined as a decrease in ADA or NAb titer and improvement in RSS.
Step 5
End of study
The study is expected to conclude by August 27, 2027. Participants will have a final assessment to evaluate the overall effectiveness of the treatment and any long-term effects.

Who can join the trial?

7 criteria

Participants must be 2 years of age or older and younger than 18 years with open growth plates in their bones. Growth plates are areas of growing tissues at the ends of long bones in children and teenagers.
Participants must have experienced a return or worsening of rickets symptoms for at least the past 3 months. Rickets is a condition that affects bone development in children. This should occur in participants who initially responded well to the treatment with asfotase alfa after at least 6 months of continuous use and are still receiving it.
Participants must have the presence of ADAs (anti-drug antibodies), which are immune system proteins that can develop in response to the treatment, with or without NAbs (neutralizing antibodies), regardless of their levels.
There must be confirmation by the Treatment Monitoring Board that both the clinical evidence and the immune-related issues mentioned above are present.
Participants can be male or female.
Female participants who can have children and male participants with partners who can have children must follow specific guidance on contraception as outlined in the study protocol.
The participant, or their legal guardian, must be able to sign an informed consent or assent form, which means they agree to follow the study's requirements and restrictions.

Who cannot join the trial?

3 criteria

Patients who do not have hypophosphatasia cannot participate. Hypophosphatasia is a rare condition that affects the development of bones and teeth.
Patients who are not experiencing an immune-mediated loss of effectiveness with their current treatment cannot participate. This means their immune system is not causing their treatment to stop working.
Patients who are not eligible for immunosuppressive therapies cannot participate. Immunosuppressive therapies are treatments that lower the activity of the immune system.

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Verified sites

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CHU Kremlin Bicêtre
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Le Kremlin-Bicetre, France

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Investigated drugs

Asfotase Alfa (STRENSIQ®)
is a medication used to treat a rare condition called hypophosphatasia, which affects the development of bones and teeth. This medication works by replacing an enzyme that is missing or not working properly in people with this condition. The goal is to help improve bone strength and growth, reducing the risk of fractures and other bone-related issues.
Immunosuppressive Therapies (IST)
are treatments that help reduce the activity of the immune system. In this study, these therapies are used to prevent the immune system from attacking the medication Asfotase Alfa, which can happen in some patients. By using immunosuppressive therapies, the study aims to maintain the effectiveness of Asfotase Alfa in treating hypophosphatasia.

What is already known about the treatment

Strensiq – Strensiq is administered as an injection under the skin, typically in the thigh, abdomen, or upper arm. It is currently used in medicine to treat hypophosphatasia, a rare genetic disorder that affects bone development. The main therapeutic indication for Strensiq is to replace an enzyme that is deficient in people with hypophosphatasia, helping to improve bone health and growth. At the molecular level, Strensiq works by providing a synthetic version of the enzyme alkaline phosphatase, which is crucial for bone mineralization. It is classified pharmacologically as an enzyme replacement therapy.

Investigated diseases

Hypophosphatasia – Hypophosphatasia is a rare genetic disorder characterized by the abnormal development of bones and teeth due to defective mineralization. It results from mutations in the gene that encodes the tissue-nonspecific alkaline phosphatase enzyme, leading to low levels of this enzyme. The disease can manifest at any age, from infancy to adulthood, with varying degrees of severity. In infants, it may present with poor feeding, failure to thrive, and soft skull bones. In children and adults, it can cause premature loss of teeth, bone pain, and frequent fractures. The progression of hypophosphatasia varies widely, with some individuals experiencing mild symptoms and others facing significant skeletal abnormalities.