Safety, Tolerability, and Immunogenicity of One Dose of NDV 3A Vaccine in People With STAT3-Mutated Hyper-IgE Syndrome
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02996448|
Recruitment Status : Active, not recruiting
First Posted : December 19, 2016
Last Update Posted : May 14, 2018
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.
To test the new vaccine NDV-3A for protection against infection from the yeast Candida and the bacterium Staphylococcus aureus (Staph).
Adults ages 18-55 who have AD-HIES
Healthy volunteers ages 18-55
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.
|Condition or disease||Intervention/treatment||Phase|
|Autosomal-dominant Hyper-IgE Syndrome||Drug: NDV-3A||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|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|
|Study Start Date :||November 17, 2016|
|Estimated Primary Completion Date :||July 22, 2018|
|Estimated Study Completion Date :||December 22, 2020|
Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.
A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.
- Percent of each group with at least a four-fold increase in anti rAls3 antibody titer. [ Time Frame: 2 weeks after vaccination ]
- Frequency of injection site and systemic AEs in AD-HIES affected patients and healthy volunteers. [ Time Frame: Throughout study participation ]
- Anti-Als3 antibody titers at 6 months after vaccination in patients with AD HIES and healthy volunteers. [ Time Frame: 6 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02996448
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Alexandra Freeman, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|