Effect of Adjuvant & Route of Administration on Safety & Immunogenicity of NDV-3 Vaccine

Phase 1

Completed

Conditions: Staphylococcal Infections
Yeast Infections
Candidiasis

Interventions: Biological: NDV-3 vaccine without alum ID
Biological: NDV-3 vaccine without alum IM
Biological: Placebo with alum IM
Biological: NDV-3 vaccine with alum IM

Registration Number: NCT01447407

Lead Sponsor: NovaDigm Therapeutics, Inc.

Brief Summary: This partially-blind, placebo controlled study is a Phase 1b study using an investigational vaccine, NDV-3, directed against Staphylococcus aureus and Candida sp. This study will compare NDV-3 administered with or without alum delivered intramuscularly (IM) at one dose level. It will also evaluate a lower dose of NDV-3 without alum delivered intradermally (ID) compared to placebo delivered ID.

Detailed Description: Preclinical studies in mice have established that several members of the Als family of proteins induce a protective immune response in mice and allow high survival rates following challenge with highly virulent doses of either Candida or S. aureus. Als3 (the antigen in the NDV-3 investigational vaccine) is the most effective member of the Als protein family in protecting mice from challenge with either Candida or S. aureus. The first Phase 1 study enrolled 40 healthy subjects that received placebo (N=10), 1 dose (N=30) or 2 doses (N=19) of the NDV-3 vaccine administered intramuscularly (IM). The vaccine was well tolerated and highly immunogenic. This study will evaluate the safety, tolerability and immunogenicity of one dose of NDV-3 vaccine formulated with and without alum given IM and also a lower dose without alum given intradermally (ID). Subjects will have follow-up visits to assess the safety tolerability and immune responses at selected time points up to 90 days post-vaccination.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 164

Inclusion Criteria

Informed of the nature of the study and have agreed to and are able to read, review, and sign the informed consent document prior to screening. The informed consent document will be written in English, therefore the volunteer must have the ability to read and communicate in English.
Completed the screening process (as described in this protocol) within 28 days prior to dosing.
Healthy male and female volunteers 18-50 years of age, inclusive, at the time of dosing.
No clinically significant deviation from normal as judged by the investigator(s) in the medical history, physical examination (including but may not be limited to an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems), vital sign assessments, 12-lead electrocardiogram (ECG), clinical laboratory assessments, and by general observations.
Female volunteers must be one of the following:
- of childbearing potential and practicing an acceptable method of birth control as judged by the Investigator(s)
- naturally postmenopausal (no menses) for at least 1 year and has a documented FSH level ≥ 40 mIU/mL
- surgically postmenopausal (bilateral oophorectomy or hysterectomy)
- sterile (surgically [bilateral tubal ligation] or the Essure® Procedure) Female volunteers that are surgically sterile or surgically postmenopausal must provide documentation of the bilateral tubal ligation, bilateral oophorectomy, or hysterectomy prior to dosing or the volunteer must agree to use a medically acceptable method of birth control. The Essure® Procedure must have been inserted at least 3 months prior with documentation of the Essure® confirmation test prior to Period I dosing. If the procedure was inserted less than 3 months prior to Period I dosing or proper documentation of the confirmation test is not provided, the volunteer must agree to use an additional medically acceptable method of birth control.

Exclusion Criteria

Reports receiving any investigational drug, investigational vaccine, or investigational device within 30 days prior to dosing.
Reports any presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease as determined by the Investigator(s).
Clinical laboratory test values outside the accepted range.
When confirmed upon additional testing, demonstrates a reactive screen for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody.
Demonstrates a positive drug screen for non-prescription drugs.
Reports a clinically significant illness during the 28 days prior to dosing (as determined by the Investigator[s]).
Reports a history of allergic response(s) to nickel or anaphylaxis (or other serious reactions) to aluminum.
Reports receiving any live attenuated vaccine including FluMist® within 6 weeks prior to dosing or any licensed inactivated vaccine within 3 weeks prior to dosing.
Reports the use of any immunosuppressive drugs, including systemic corticosteroids, within 4 weeks prior to dosing.
Reports the use of any medications or treatments that may alter immune responses to the study vaccine within 3 weeks prior to dosing (eg, cyclosporine, tacrolimus, cytotoxic drugs, immune globulin, Bacillus Calmette-Guerin [BCG], monoclonal antibodies, radiation therapy).
Reports a history of clinically significant allergies including food or drug allergies or anaphylaxis (or other serious reactions) to vaccines.
Reports a history of drug or alcohol addiction or abuse within the past year.
Reports receiving any blood products within 3 months prior to dosing and throughout the study.
Reports donating blood within 28 days prior to dosing. All subjects will be advised not to donate blood for four weeks after completing the study.
Reports donating plasma (e.g. plasmapheresis) within 14 days prior to dosing. All subjects will be advised not to donate plasma for four weeks after completing the study.
Demonstrates, in the opinion of study staff, veins unsuitable for repeated venipuncture (e.g. veins difficult to locate, access, or puncture; veins with a tendency to rupture during or after puncture).
Pregnant, lactating, breastfeeding, or intends to become pregnant over the course of the study.
Demonstrates a positive pregnancy screen.
Reports smoking or using tobacco products or is currently using nicotine products (patches, gums, etc). Thirty (30) days abstinence prior to dosing is required.
Any other medical and/or social (e.g. uncooperative or non-compliant) reason which, in the opinion of the investigator(s), would prevent participation in the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NDV-3 vaccine without alum ID	NDV-3 vaccine without alum ID	30 ug Als3 in PBS per dose, one dose administered ID
NDV-3 vaccine without alum IM	NDV-3 vaccine without alum IM	300 ug Als3 in PBS per dose, one dose administered IM
Placebo IM	Placebo with alum IM	0.5 mg Al as alum in PBS per dose, one dose administered IM
NDV-3 vaccine with alum IM	NDV-3 vaccine with alum IM	300 ug Als3 and 0.5 mg Al as alum in PBS per dose, one dose administered IM

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events	Up to 90 days post-vaccination	The primary objective of this study is to assess the safety of a single dose of NDV-3 vaccine, administered either IM with or without alum adjuvant at one dose level or ID at a lower dose level, compared to placebo. Clinical evaluations will be assessed on each subject at selected time points up to 90 days post-vaccination.

Secondary Outcome Measures

Name	Time	Method
Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g)	Baseline, Day 7, Day 14, Day 28, Day 90/Exit	A secondary objective is to compare the cellular immune response for Als3-specific production of IFN-g from PBMCs between the 2 dose levels, routes of administration, and effects of alum adjuvant, at selected time points up to 90 days post-vaccination. The IFN-g cellular immune responses will be evaluated by ELISpot using approximately 200,000 PBMCs per well. A positive response was defined as a sample with greater than 20 spot forming units per 10\^6 PBMCs.
Immunogenicity - Serum Anti-Als3 IgG	Baseline, Day 7, Day 14, Day 28, Day 90/Exit	A secondary objective is to compare the serum IgG immune response between the 2 dose levels, routes of administration, and effects of alum adjuvant, at selected time points up to 90 days post-vaccination. Serum IgG will be evaluated by ELISA on serial-diluted samples, resulting in titer values of reciprocal dilution at which the ELISA readout is three times greater than the assay background value.
Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1	Baseline, Day 7, Day 14, Day 28, Day 90/Exit	A secondary objective is to compare the cervicovaginal wash IgA1 immune response between the 2 dose levels, routes of administration, and effects of alum adjuvant, at selected time points up to 90 days post-vaccination. Cervicovaginal wash IgA1 will be evaluated by ELISA on serial-diluted samples, resulting in titer values of reciprocal dilution at which the ELISA readout is three times greater than the assay background value.
Immunogenicity - Serum Anti-Als3 IgA1	Baseline, Day 7, Day 14, Day 28, Day 90/Exit	A secondary objective is to compare the serum IgA1 immune response between the 2 dose levels, routes of administration, and effects of alum adjuvant, at selected time points up to 90 days post-vaccination. Serum IgA1 will be evaluated by ELISA on serial-diluted samples, resulting in titer values of reciprocal dilution at which the ELISA readout is three times greater than the assay background value.
Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG	Baseline, Day 7, Day 14, Day 28, Day 90/Exit	A secondary objective is to compare the cervicovaginal wash IgG immune response between the 2 dose levels, routes of administration, and effects of alum adjuvant, at selected time points up to 90 days post-vaccination. Cervicovaginal wash IgG will be evaluated by ELISA on serial-diluted samples, resulting in titer values of reciprocal dilution at which the ELISA readout is three times greater than the assay background value.
Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A)	Baseline, Day 7, Day 14, Day 28, Day 90/Exit	A secondary objective is to compare the cellular immune response for Als3-specific production of IL-17A from PBMCs between the 2 dose levels, routes of administration, and effects of alum adjuvant, at selected time points up to 90 days post-vaccination. The IL-17A cellular immune responses will be evaluated by ELISpot using approximately 200,000 PBMCs per well. A positive response was defined as a sample with greater than 20 spot forming units per 10\^6 PBMCs.