Safety, Tolerability, and Immunogenicity of One Dose of NDV 3A Vaccine in People With STAT3-Mutated Hyper-IgE Syndrome

Phase 2

Terminated

• Conditions: Autosomal-dominant Hyper-IgE Syndrome
• Interventions: Drug: NDV-3A

• Registration Number: NCT02996448
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

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.

Detailed Description

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 Timeline

• Study Start: 2016-11-17
• Study First Submitted: 2016-12-16
• Study First Submitted QC: 2016-12-16
• Study First Posted: 2016-12-19
• Primary Completion: 2018-07-22
• Status Verified: 2018-10
• Study Completion: 2018-10-09
• Results First Submitted: 2020-06-22
• Results First Submitted QC: 2020-06-22
• Last Update Submitted: 2020-06-22
• Results First Posted: 2020-06-30
• Last Update Posted: 2020-06-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NDV 3A vaccine	NDV-3A	Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.

Primary Outcome Measures

Name	Time	Method
Percent of Each Group With at Least a Four-fold Increase in Anti rAls3 Antibody Titer.	2 weeks after vaccination	Antibody titer

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Serious Adverse Events That Led to Study Termination.	Up to 6 months
Anti-Als3 Antibody Titers at 6 Months After Vaccination in Patients With AD HIES and Healthy Volunteers.	6 months

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States