Candidiasis, Staphylococcal Infections, Yeast Infections
Conditions
Keywords
Staphylococcal infections, Yeast infections, Candidiasis
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.
Interventions
BIOLOGICALNDV-3 vaccine with alum IM
One dose administered IM
BIOLOGICALNDV-3 vaccine without alum IM
One dose administered IM
BIOLOGICALPlacebo with alum IM
One dose administered ID
BIOLOGICALNDV-3 vaccine without alum ID
One dose administered ID
Sponsors
United States Department of Defense
NovaDigm Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. 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. 2. Completed the screening process (as described in this protocol) within 28 days prior to dosing. 3. Healthy male and female volunteers 18-50 years of age, inclusive, at the time of dosing. 4. 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. 5. 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
1. Reports receiving any investigational drug, investigational vaccine, or investigational device within 30 days prior to dosing. 2. 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). 3. Clinical laboratory test values outside the accepted range. 4. When confirmed upon additional testing, demonstrates a reactive screen for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody. 5. Demonstrates a positive drug screen for non-prescription drugs. 6. Reports a clinically significant illness during the 28 days prior to dosing (as determined by the Investigator\[s\]). 7. Reports a history of allergic response(s) to nickel or anaphylaxis (or other serious reactions) to aluminum. 8. 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. 9. Reports the use of any immunosuppressive drugs, including systemic corticosteroids, within 4 weeks prior to dosing. 10. 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). 11. Reports a history of clinically significant allergies including food or drug allergies or anaphylaxis (or other serious reactions) to vaccines. 12. Reports a history of drug or alcohol addiction or abuse within the past year. 13. Reports receiving any blood products within 3 months prior to dosing and throughout the study. 14. 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. 15. 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. 16. 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). 17. Pregnant, lactating, breastfeeding, or intends to become pregnant over the course of the study. 18. Demonstrates a positive pregnancy screen. 19. Reports smoking or using tobacco products or is currently using nicotine products (patches, gums, etc). Thirty (30) days abstinence prior to dosing is required. 20. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 - 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 - 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 - 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 - 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. |
Countries
United States
Participant flow
Pre-assignment details
Four subjects withdrew before completing Day 28 and were replaced. One subject withdrew before the last visit. While this subject is not considered to have completed the study, data from this subject are included in the immunogenicity and culture results.
Participants by arm
| Arm | Count |
|---|---|
| NDV-3 Vaccine With Alum NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM | 41 |
| NDV-3 Vaccine Without Alum NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM | 40 |
| Placebo Placebo administered ID: One dose saline placebo administered ID | 41 |
| NDV-3 Vaccine ID NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID | 42 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | NDV-3 Vaccine With Alum | NDV-3 Vaccine Without Alum | Placebo | NDV-3 Vaccine ID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 31.8 years | 30.1 years | 32.3 years | 31.0 years | 31.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 40 Participants | 41 Participants | 41 Participants | 163 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 37 Participants | 36 Participants | 38 Participants | 149 Participants |
| Sex: Female, Male Female | 33 Participants | 33 Participants | 34 Participants | 34 Participants | 134 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 7 Participants | 8 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 40 | 0 / 41 | 0 / 42 |
| other Total, other adverse events | 35 / 41 | 33 / 40 | 30 / 41 | 36 / 42 |
| serious Total, serious adverse events | 0 / 41 | 0 / 40 | 0 / 41 | 0 / 42 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events
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.
Time frame: Up to 90 days post-vaccination
Population: All subjects completing study. Additionally, a subject in Group 4 withdrew from the study before the very last visit, so while this subject is not considered to have completed the study, immunogenicity and culture data for this subject were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NDV-3 Vaccine With Alum | Number of Participants With Treatment Emergent Adverse Events | >=1 TEAE | 35 participants |
| NDV-3 Vaccine With Alum | Number of Participants With Treatment Emergent Adverse Events | >=1 severe TEAE | 2 participants |
| NDV-3 Vaccine With Alum | Number of Participants With Treatment Emergent Adverse Events | >=1 severe drug-related TEAE | 0 participants |
| NDV-3 Vaccine With Alum | Number of Participants With Treatment Emergent Adverse Events | DIscontinued for >=1 TEAE | 0 participants |
| NDV-3 Vaccine Without Alum | Number of Participants With Treatment Emergent Adverse Events | >=1 severe TEAE | 0 participants |
| NDV-3 Vaccine Without Alum | Number of Participants With Treatment Emergent Adverse Events | >=1 severe drug-related TEAE | 0 participants |
| NDV-3 Vaccine Without Alum | Number of Participants With Treatment Emergent Adverse Events | DIscontinued for >=1 TEAE | 0 participants |
| NDV-3 Vaccine Without Alum | Number of Participants With Treatment Emergent Adverse Events | >=1 TEAE | 33 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | >=1 severe drug-related TEAE | 0 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | >=1 severe TEAE | 4 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | DIscontinued for >=1 TEAE | 0 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | >=1 TEAE | 30 participants |
| NDV-3 Vaccine ID | Number of Participants With Treatment Emergent Adverse Events | DIscontinued for >=1 TEAE | 0 participants |
| NDV-3 Vaccine ID | Number of Participants With Treatment Emergent Adverse Events | >=1 severe TEAE | 2 participants |
| NDV-3 Vaccine ID | Number of Participants With Treatment Emergent Adverse Events | >=1 TEAE | 36 participants |
| NDV-3 Vaccine ID | Number of Participants With Treatment Emergent Adverse Events | >=1 severe drug-related TEAE | 0 participants |
Secondary
Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1
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.
Time frame: Baseline, Day 7, Day 14, Day 28, Day 90/Exit
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NDV-3 Vaccine With Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 28 | 36 Titer | Standard Deviation 3.82 |
| NDV-3 Vaccine With Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 7 | 5 Titer | Standard Deviation 2.87 |
| NDV-3 Vaccine With Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 90/Exit | 15 Titer | Standard Deviation 3.18 |
| NDV-3 Vaccine With Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 14 | 83 Titer | Standard Deviation 4.5 |
| NDV-3 Vaccine With Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Baseline | 3 Titer | Standard Deviation 2.03 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 14 | 29 Titer | Standard Deviation 6.48 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 28 | 25 Titer | Standard Deviation 6.72 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 90/Exit | 8 Titer | Standard Deviation 3.27 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 7 | 7 Titer | Standard Deviation 6.64 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Baseline | 3 Titer | Standard Deviation 2.08 |
| Placebo | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 14 | 3 Titer | Standard Deviation 1.64 |
| Placebo | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Baseline | 3 Titer | Standard Deviation 2.24 |
| Placebo | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 7 | 3 Titer | Standard Deviation 1.45 |
| Placebo | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 28 | 3 Titer | Standard Deviation 2.4 |
| Placebo | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 90/Exit | 3 Titer | Standard Deviation 1.98 |
| NDV-3 Vaccine ID | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 28 | 8 Titer | Standard Deviation 4.56 |
| NDV-3 Vaccine ID | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 7 | 4 Titer | Standard Deviation 2.71 |
| NDV-3 Vaccine ID | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Baseline | 3 Titer | Standard Deviation 2.5 |
| NDV-3 Vaccine ID | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 14 | 12 Titer | Standard Deviation 4.23 |
| NDV-3 Vaccine ID | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1 | Day 90/Exit | 5 Titer | Standard Deviation 3.4 |
Secondary
Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG
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.
Time frame: Baseline, Day 7, Day 14, Day 28, Day 90/Exit
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NDV-3 Vaccine With Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 28 | 44 Titer | Standard Deviation 5.85 |
| NDV-3 Vaccine With Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 7 | 4 Titer | Standard Deviation 3.98 |
| NDV-3 Vaccine With Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 90/Exit | 20 Titer | Standard Deviation 4.93 |
| NDV-3 Vaccine With Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 14 | 78 Titer | Standard Deviation 7.12 |
| NDV-3 Vaccine With Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Baseline | 2 Titer | Standard Deviation 1.5 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 14 | 26 Titer | Standard Deviation 7.5 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 28 | 26 Titer | Standard Deviation 7.09 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 90/Exit | 13 Titer | Standard Deviation 4.65 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 7 | 6 Titer | Standard Deviation 5.84 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Baseline | 2 Titer | Standard Deviation 1.55 |
| Placebo | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 14 | 3 Titer | Standard Deviation 1.99 |
| Placebo | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Baseline | 3 Titer | Standard Deviation 2.12 |
| Placebo | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 7 | 2 Titer | Standard Deviation 1.61 |
| Placebo | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 28 | 3 Titer | Standard Deviation 2.2 |
| Placebo | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 90/Exit | 3 Titer | Standard Deviation 2.11 |
| NDV-3 Vaccine ID | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 28 | 8 Titer | Standard Deviation 4.63 |
| NDV-3 Vaccine ID | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 7 | 3 Titer | Standard Deviation 2.45 |
| NDV-3 Vaccine ID | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Baseline | 3 Titer | Standard Deviation 1.98 |
| NDV-3 Vaccine ID | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 14 | 8 Titer | Standard Deviation 4.27 |
| NDV-3 Vaccine ID | Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG | Day 90/Exit | 6 Titer | Standard Deviation 4.35 |
Secondary
Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g)
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.
Time frame: Baseline, Day 7, Day 14, Day 28, Day 90/Exit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NDV-3 Vaccine With Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Baseline | 7 Participants |
| NDV-3 Vaccine With Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 7 | 27 Participants |
| NDV-3 Vaccine With Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 14 | 19 Participants |
| NDV-3 Vaccine With Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 90/Exit | 25 Participants |
| NDV-3 Vaccine Without Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 7 | 25 Participants |
| NDV-3 Vaccine Without Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 14 | 21 Participants |
| NDV-3 Vaccine Without Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 90/Exit | 18 Participants |
| NDV-3 Vaccine Without Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Baseline | 9 Participants |
| Placebo | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 14 | 5 Participants |
| Placebo | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 7 | 10 Participants |
| Placebo | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 90/Exit | 9 Participants |
| Placebo | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Baseline | 7 Participants |
| NDV-3 Vaccine ID | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 90/Exit | 14 Participants |
| NDV-3 Vaccine ID | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 7 | 20 Participants |
| NDV-3 Vaccine ID | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Baseline | 5 Participants |
| NDV-3 Vaccine ID | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g) | Day 14 | 20 Participants |
Secondary
Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A)
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.
Time frame: Baseline, Day 7, Day 14, Day 28, Day 90/Exit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NDV-3 Vaccine With Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Baseline | 6 Participants |
| NDV-3 Vaccine With Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 7 | 22 Participants |
| NDV-3 Vaccine With Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 14 | 15 Participants |
| NDV-3 Vaccine With Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 90/Exit | 17 Participants |
| NDV-3 Vaccine Without Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 7 | 19 Participants |
| NDV-3 Vaccine Without Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 14 | 17 Participants |
| NDV-3 Vaccine Without Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 90/Exit | 15 Participants |
| NDV-3 Vaccine Without Alum | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Baseline | 10 Participants |
| Placebo | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 14 | 7 Participants |
| Placebo | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 7 | 8 Participants |
| Placebo | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 90/Exit | 18 Participants |
| Placebo | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Baseline | 12 Participants |
| NDV-3 Vaccine ID | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 90/Exit | 23 Participants |
| NDV-3 Vaccine ID | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 7 | 13 Participants |
| NDV-3 Vaccine ID | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Baseline | 9 Participants |
| NDV-3 Vaccine ID | Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A) | Day 14 | 16 Participants |
Secondary
Immunogenicity - Serum Anti-Als3 IgA1
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.
Time frame: Baseline, Day 7, Day 14, Day 28, Day 90/Exit
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NDV-3 Vaccine With Alum | Immunogenicity - Serum Anti-Als3 IgA1 | Day 28 | 43790 Titer | Standard Deviation 2.59 |
| NDV-3 Vaccine With Alum | Immunogenicity - Serum Anti-Als3 IgA1 | Day 7 | 7643 Titer | Standard Deviation 6.61 |
| NDV-3 Vaccine With Alum | Immunogenicity - Serum Anti-Als3 IgA1 | Day 90/Exit | 20656 Titer | Standard Deviation 2.51 |
| NDV-3 Vaccine With Alum | Immunogenicity - Serum Anti-Als3 IgA1 | Day 14 | 69616 Titer | Standard Deviation 3.1 |
| NDV-3 Vaccine With Alum | Immunogenicity - Serum Anti-Als3 IgA1 | Baseline | 573 Titer | Standard Deviation 4.07 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Serum Anti-Als3 IgA1 | Day 14 | 34946 Titer | Standard Deviation 6.77 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Serum Anti-Als3 IgA1 | Day 28 | 19999 Titer | Standard Deviation 5.36 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Serum Anti-Als3 IgA1 | Day 90/Exit | 10698 Titer | Standard Deviation 4.61 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Serum Anti-Als3 IgA1 | Day 7 | 5497 Titer | Standard Deviation 7.01 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Serum Anti-Als3 IgA1 | Baseline | 480 Titer | Standard Deviation 3.44 |
| Placebo | Immunogenicity - Serum Anti-Als3 IgA1 | Day 14 | 429 Titer | Standard Deviation 3.93 |
| Placebo | Immunogenicity - Serum Anti-Als3 IgA1 | Baseline | 418 Titer | Standard Deviation 3.72 |
| Placebo | Immunogenicity - Serum Anti-Als3 IgA1 | Day 7 | 431 Titer | Standard Deviation 3.69 |
| Placebo | Immunogenicity - Serum Anti-Als3 IgA1 | Day 28 | 412 Titer | Standard Deviation 3.86 |
| Placebo | Immunogenicity - Serum Anti-Als3 IgA1 | Day 90/Exit | 404 Titer | Standard Deviation 3.78 |
| NDV-3 Vaccine ID | Immunogenicity - Serum Anti-Als3 IgA1 | Day 28 | 7400 Titer | Standard Deviation 6.33 |
| NDV-3 Vaccine ID | Immunogenicity - Serum Anti-Als3 IgA1 | Day 7 | 1640 Titer | Standard Deviation 6.56 |
| NDV-3 Vaccine ID | Immunogenicity - Serum Anti-Als3 IgA1 | Baseline | 550 Titer | Standard Deviation 4.93 |
| NDV-3 Vaccine ID | Immunogenicity - Serum Anti-Als3 IgA1 | Day 14 | 9356 Titer | Standard Deviation 6014 |
| NDV-3 Vaccine ID | Immunogenicity - Serum Anti-Als3 IgA1 | Day 90/Exit | 3641 Titer | Standard Deviation 5.18 |
Secondary
Immunogenicity - Serum Anti-Als3 IgG
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.
Time frame: Baseline, Day 7, Day 14, Day 28, Day 90/Exit
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NDV-3 Vaccine With Alum | Immunogenicity - Serum Anti-Als3 IgG | Day 28 | 38898 Titer | Standard Deviation 2.83 |
| NDV-3 Vaccine With Alum | Immunogenicity - Serum Anti-Als3 IgG | Day 7 | 4447 Titer | Standard Deviation 6.31 |
| NDV-3 Vaccine With Alum | Immunogenicity - Serum Anti-Als3 IgG | Day 90/Exit | 20853 Titer | Standard Deviation 3.24 |
| NDV-3 Vaccine With Alum | Immunogenicity - Serum Anti-Als3 IgG | Day 14 | 44675 Titer | Standard Deviation 3.04 |
| NDV-3 Vaccine With Alum | Immunogenicity - Serum Anti-Als3 IgG | Baseline | 372 Titer | Standard Deviation 3.12 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Serum Anti-Als3 IgG | Day 14 | 22675 Titer | Standard Deviation 6.58 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Serum Anti-Als3 IgG | Day 28 | 19220 Titer | Standard Deviation 6 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Serum Anti-Als3 IgG | Day 90/Exit | 11771 Titer | Standard Deviation 5.93 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Serum Anti-Als3 IgG | Day 7 | 3070 Titer | Standard Deviation 6.71 |
| NDV-3 Vaccine Without Alum | Immunogenicity - Serum Anti-Als3 IgG | Baseline | 320 Titer | Standard Deviation 3.07 |
| Placebo | Immunogenicity - Serum Anti-Als3 IgG | Day 14 | 370 Titer | Standard Deviation 2.89 |
| Placebo | Immunogenicity - Serum Anti-Als3 IgG | Baseline | 363 Titer | Standard Deviation 2.93 |
| Placebo | Immunogenicity - Serum Anti-Als3 IgG | Day 7 | 365 Titer | Standard Deviation 2.81 |
| Placebo | Immunogenicity - Serum Anti-Als3 IgG | Day 28 | 377 Titer | Standard Deviation 2.93 |
| Placebo | Immunogenicity - Serum Anti-Als3 IgG | Day 90/Exit | 347 Titer | Standard Deviation 2.71 |
| NDV-3 Vaccine ID | Immunogenicity - Serum Anti-Als3 IgG | Day 28 | 4513 Titer | Standard Deviation 6.6 |
| NDV-3 Vaccine ID | Immunogenicity - Serum Anti-Als3 IgG | Day 7 | 874 Titer | Standard Deviation 5.25 |
| NDV-3 Vaccine ID | Immunogenicity - Serum Anti-Als3 IgG | Baseline | 375 Titer | Standard Deviation 3.53 |
| NDV-3 Vaccine ID | Immunogenicity - Serum Anti-Als3 IgG | Day 14 | 5153 Titer | Standard Deviation 6.97 |
| NDV-3 Vaccine ID | Immunogenicity - Serum Anti-Als3 IgG | Day 90/Exit | 3282 Titer | Standard Deviation 5.55 |