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
| Verified date | October 2018 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 3 |
| Est. completion date | October 9, 2018 |
| Est. primary completion date | July 22, 2018 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 18 Years to 55 Years |
| Eligibility |
- INCLUSION CRITERIA: 1. Age 18-55 years. 2. For healthy volunteers: in general good health, without significant medical illness, physical exam findings, or significant laboratory abnormalities as determined by the investigator. 3. For participants with AD-HIES: confirmation of diagnosis with a STAT3 mutation. 4. 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. 5. Agree to allow storage of biological samples for future research. EXCLUSION CRITERIA: 1. Has a history of allergic response or other serious reaction to aluminum and/or yeast products. 2. 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. 3. 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). 4. Has an active infection with hepatitis B, hepatitis C, or HIV. 5. 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. 6. Has received or is planning to receive any other live vaccine within three weeks before vaccination or for three weeks after vaccination. 7. Self-reported current alcohol abuse or addiction. 8. Self-reported current illicit drug abuse or addiction, or drug screen positive for illicit drugs. 9. 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. 10. Current or planned use within 2 weeks before vaccination of immune globulin replacement. 11. Has any of the following laboratory abnormalities at the screening visit: 1. Alanine transaminase (ALT), aspartate transaminase (AST), and/or alkaline phosphatase (ALP) > 1.5 times the upper limit of normal (ULN). 2. Total bilirubin level > 1.5 times the ULN 3. Serum creatinine level > 1.5 times the ULN 4. Absolute neutrophil count < 750 cells/microliter 5. Hemoglobin < 9 mg/dL 6. Platelet count < 100,000 12. Refusal or inability to comply with study procedures to the extent that it is potentially harmful to the participant or to the integrity of the study data. 13. Has donated blood/plasma within four weeks before vaccination. 14. Is pregnant or breastfeeding, or intends to become pregnant over the course of the study. 15. Is unable to commit to the follow-up visits and or has unreliable access to a telephone for follow-up contacts, either by self-admission (self-reporting) or in the opinion of the investigator. 16. Any other condition the investigator believes would interfere with the participant s ability to provide informed consent, comply with study instructions, or that might confound the interpretation of the study results or put the participant at undue risk. |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
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. Review. — View Citation
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. Review. — View Citation
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. Epub 2006 Jun 6. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percent of Each Group With at Least a Four-fold Increase in Anti rAls3 Antibody Titer. | Antibody titer | 2 weeks after vaccination | |
| Secondary | Number of Participants With Serious Adverse Events That Led to Study Termination. | Up to 6 months | ||
| Secondary | Anti-Als3 Antibody Titers at 6 Months After Vaccination in Patients With AD HIES and Healthy Volunteers. | 6 months |