Ongoing Clinical Trials for Immunodeficiency Congenital
Currently, there are 2 ongoing clinical trials for congenital immunodeficiency conditions. These studies are testing new treatments for rare genetic disorders that affect the immune system, including WHIM Syndrome and LRBA deficiency. The trials are taking place in several European countries and aim to evaluate the safety and effectiveness of investigational medications.
Clinical trial locations
- Belgium
- Denmark
- France
- Italy
- Netherlands
- Spain
Study on Mavorixafor for Treating WHIM Syndrome in Patients
This trial focuses on WHIM Syndrome, a rare genetic disorder that weakens the immune system. The condition is named after its main symptoms: Warts, Hypogammaglobulinemia (low antibody levels), Infections, and Myelokathexis (retention of white blood cells in bone marrow). People with this syndrome experience recurrent bacterial infections because their neutrophils, a type of white blood cell essential for fighting infections, remain trapped in the bone marrow instead of circulating in the bloodstream.
Main inclusion criteria:
- Participants must be at least 12 years old
- Must have a confirmed genetic mutation in the CXCR4 gene consistent with WHIM Syndrome
- Must have an Absolute Neutrophil Count of 400 cells per microliter or less during screening, without signs of infection
- Must agree to use highly effective birth control
- Must be willing and able to follow all study procedures
- For participants under 18 years old (or under 16 in some regions), both parental consent and the participant’s assent are required
Main exclusion criteria:
- Individuals without a confirmed diagnosis of WHIM Syndrome
- Those currently participating in another clinical trial
- Individuals with other serious medical conditions that could make participation unsafe
- Pregnant or breastfeeding women
- People with known allergies to the study medication or its ingredients
- Those unable to comply with study procedures and follow-up requirements
Study focus and design: The trial is divided into two parts. In the first part, which lasts 12 months, participants are randomly assigned to receive either Mavorixafor or a placebo. This helps researchers compare how well the medication works. The main goal is to see how long neutrophil counts can remain above a certain level, which is measured every three months. In the second part, all participants receive Mavorixafor to assess its long-term safety and tolerability through regular blood tests and physical examinations.
Investigational drug: Mavorixafor is an oral medication taken as a hard capsule. It works by blocking the CXCR4 receptor on cells, which helps release neutrophils from the bone marrow into the bloodstream where they can fight infections more effectively.
Trial of Ataluren for Severe Common Variable Immunodeficiency with Autoimmunity in Patients with LRBA Deficiency
This trial studies LRBA deficiency, a rare genetic disorder affecting the immune system caused by mutations in the LRBA gene. This condition leads to an excessive number of lymphocytes, a type of immune cell, which can cause autoimmune problems, low antibody levels, and recurrent infections. People with LRBA deficiency often experience chronic diarrhea, gastrointestinal issues, and have an increased risk of developing lymphoma. The excessive lymphocytes can infiltrate various organs, particularly the gut, lungs, and brain.
Main inclusion criteria:
- Must have confirmed LRBA deficiency
- Must have homozygous nonsense mutations (meaning both copies of the gene have specific changes that stop it from working properly)
- Must be male
- Must be at least 3 years old
Main exclusion criteria:
- Individuals without a confirmed diagnosis of LRBA deficiency
- Female participants (the study is only open to males)
- Children under 3 years of age
- Individuals considered part of vulnerable populations who might need special protection or care
Study focus and design: This is a single-patient trial designed to evaluate whether Ataluren can reduce symptoms associated with LRBA deficiency, such as excessive lymphocyte growth and chronic diarrhea. The study will monitor improvements in quality of life, weight, frequency of diarrhea episodes, and reduction in hospital visits. Researchers will also examine specific immune system markers in the blood to see if there are changes in protein expression. The trial is expected to continue until August 2027, allowing for comprehensive long-term monitoring.
Investigational drug: Ataluren is taken orally as granules for oral suspension, available in 1000 mg and 250 mg dosages. It works at the molecular level by allowing cells to read through premature stop signals in genetic instructions, enabling the production of full-length, functional proteins. This mechanism may help restore some immune system function in patients with LRBA deficiency caused by nonsense mutations.
Summary
These two clinical trials represent important research efforts in rare congenital immunodeficiency disorders. The first trial, testing Mavorixafor for WHIM Syndrome, is a larger international study taking place across five European countries: Italy, Denmark, Netherlands, France, and Spain. It follows a traditional randomized, placebo-controlled design before transitioning to an open-label phase where all participants receive the active treatment.
The second trial, testing Ataluren for LRBA deficiency, is notably different as it is a single-patient study taking place in Belgium. This reflects the extremely rare nature of this particular genetic condition and the challenges of conducting research in ultra-rare diseases. The trial is limited to male participants with specific genetic mutations.
Both trials focus on oral medications that work through different mechanisms to address the underlying causes of these immune system disorders. While Mavorixafor aims to mobilize neutrophils from the bone marrow, Ataluren works to restore protein production at the genetic level. These studies highlight the ongoing efforts to develop targeted treatments for rare immunodeficiency conditions that have limited therapeutic options.