Autosomal-dominant Hyper-IgE Syndrome Clinical Trial
Official title:
A Phase 2a Study to Evaluate the Safety, Tolerability, and Immunogenicity of One Dose of NDV-3A Vaccine in Patients With STAT3-Mutated Hyper-IgE Syndrome
Background:
AD-HIES is a disease that weakens the immune system. It puts people at risk for infections,
particularly Staph and Candida infections. Researchers want to test a vaccine that may help
keep people from getting these infections, which would help people with AD-HIES.
Objective:
To test the new vaccine NDV-3A for protection against infection from the yeast Candida and
the bacterium Staphylococcus aureus (Staph).
Eligibility:
Adults ages 18-55 who have AD-HIES
Healthy volunteers ages 18-55
Design:
Participants will have 6-7 study visits over 6-7 months. They will also be contacted by phone
in between some visits.
Participants will be screened with a medical history, physical exam, and blood and urine
tests.
Participants will have 2 baseline visits. They will have repeat the screening tests. They
will have samples of saliva, stool, skin, mucus (oral, nasal, and/or vaginal) collected.
Vaginal and stool samples are optional. Any eczema on their skin will be looked at.
Participants will fill out symptom diary cards to record how they feel.
Participants will have the NDV-3A vaccine injected into a muscle in the arm.
Participants will return the next 2 days. They will have a physical exam. Blood will be
collected.
Participants will have 2 more follow-up visits at the NIH. They will have a physical exam.
They will have blood, saliva, stool, skin, vaginal fluid, and/or mucus samples collected.
Vaginal and stool samples are optional.
Participants will be called once a month for 5 months after the vaccination. There is an
optional visit about 6 weeks after the vaccination. Participants will provide a blood sample
at this visit.
Autosomal-dominant hyper-IgE syndrome (AD-HIES) is characterized by recurrent Staphylococcus
aureus and Candida epithelial infections, which is thought to be due, in part, to a lack of
Th17 cell differentiation, thus impairing epithelial immunity. Treatment of AD-HIES is
primarily supportive with prophylactic antibiotics; however, this is limited by microbial
resistance and intolerance of medications, and infections do still occur. Immunological
intervention with a vaccine could improve quality of life by preventing these infections
altogether.
The NDV-3A vaccine consists of a recombinant protein derived from the Candida Als3 adhesion
protein. This protein is homologous to surface proteins on S aureus and has been shown in
preclinical studies to protect against both intravascular and subcutaneous challenge with S
aureus. Therefore, NDV-3A represents not only the first antifungal vaccine, but also the
first vaccine to provide cross-kingdom protection. In Phase 1 and Phase 2 studies in healthy
volunteers (150 receiving vaccine), the safety profile of this vaccine is very reassuring as
the vaccine elicits a strong antibody response after a single dose in all vaccinees as well
as a Th1 and/or Th17 response in the majority of vaccinees. We will enroll 20 healthy adult
volunteers and 20 adults with AD-HIES in an open-label, single-dose study to assess the
immunological response to and the safety/tolerability of the NDV-3A vaccine. We anticipate an
increase in baseline anti-Als3 IgG within 2 weeks post-vaccination.
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