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

NCT02996448 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 17001717-I-0017
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Autosomal-dominant Hyper-IgE Syndrome

Keywords

AD-HIES; Anti-rAls3 Antibody; Staphylococcus Aureus; Candida Albicans; RNA Transcriptome

Outcome Measures

Primary Outcomes (1)

• Percent of Each Group With at Least a Four-fold Increase in Anti rAls3 Antibody Titer.

  Antibody titer

  2 weeks after vaccination

Secondary Outcomes (2)

• 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

Study Arms (1)

NDV 3A vaccine

EXPERIMENTAL

Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.

Drug: NDV-3A

Interventions

NDV-3A DRUG

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.

NDV 3A vaccine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-55 years.
• For healthy volunteers: in general good health, without significant medical illness, physical exam findings, or significant laboratory abnormalities as determined by the investigator.
• For participants with AD-HIES: confirmation of diagnosis with a STAT3 mutation.
• Participants who can get pregnant must be willing to use an acceptable form of contraception for the duration of participation and have a negative pregnancy test at screening.
• Agree to allow storage of biological samples for future research.

You may not qualify if:

• Has a history of allergic response or other serious reaction to aluminum and/or yeast products.
• Has a history of clinically significant allergy including anaphylaxis or other serious reaction to food, vaccines, or other drugs, that in the opinion of the investigator, might put the participant at undue risk.
• Has an active infection (such as S aureus abscess, pneumonia, acute Candida mucocutaneous infection). Baseline state of chronic infections will be considered by the PI (eg, chronic Pseudomonas infection in lung).
• Has an active infection with hepatitis B, hepatitis C, or HIV.
• Has received or is planning to receive any investigational drug, investigational vaccine, or investigational device within four weeks prior to vaccination, or at any other time during their participation in the study.
• Has received or is planning to receive any other live vaccine within three weeks before vaccination or for three weeks after vaccination.
• Self-reported current alcohol abuse or addiction.
• Self-reported current illicit drug abuse or addiction, or drug screen positive for illicit drugs.
• Current or planned use, within 3 weeks before vaccination, of any medications or treatments that may alter immune responses to the study vaccine (eg, immunosuppressive medications including systemic corticosteroids, cyclosporine, tacrolimus, cytotoxic drugs, Bacillus Calmette-Guerin, monoclonal antibodies, or radiation therapy). Topical, intranasal, or inhaled immunosuppressants such as corticosteroids will be allowed.
• Current or planned use within 2 weeks before vaccination of immune globulin replacement.
• Has any of the following laboratory abnormalities at the screening visit:
• Alanine transaminase (ALT), aspartate transaminase (AST), and/or alkaline
• phosphatase (ALP) \> 1.5 times the upper limit of normal (ULN).
• Total bilirubin level \> 1.5 times the ULN
• Serum creatinine level \> 1.5 times the ULN

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012 Feb;1250:25-32. doi: 10.1111/j.1749-6632.2011.06387.x. Epub 2012 Jan 23.

  PMID: 22268731 BACKGROUND

• Spellberg BJ, Ibrahim AS, Avanesian V, Fu Y, Myers C, Phan QT, Filler SG, Yeaman MR, Edwards JE Jr. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J Infect Dis. 2006 Jul 15;194(2):256-60. doi: 10.1086/504691. Epub 2006 Jun 6.

  PMID: 16779733 BACKGROUND

• Liu Y, Filler SG. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot Cell. 2011 Feb;10(2):168-73. doi: 10.1128/EC.00279-10. Epub 2010 Nov 29.

  PMID: 21115738 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Job Syndrome; Staphylococcal Infections

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Alexandra Freeman
• Organization: NIAID, NIH

freemaal@mail.nih.gov

301-594-9045

Study Officials

• Alexandra Freeman, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: December 19, 2016
• Study Start: November 17, 2016
• Primary Completion: July 22, 2018
• Study Completion: October 9, 2018
• Last Updated: June 30, 2020
• Results First Posted: June 30, 2020

Record last verified: 2018-10

Locations

US (1)