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

• Sponsor: NovaDigm Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01447407
• Collaborator: United States Department of Defense (U.S. Fed)
• Enrollment: 164
• Location: 1
• Arms: 4
• Duration (Months): 15
• Patients Per Site Per Month: 10.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Staphylococcal Infections; Yeast Infections; Candidiasis	Biological: NDV-3 vaccine with alum IM; Biological: NDV-3 vaccine without alum IM; Biological: Placebo with alum IM; Biological: NDV-3 vaccine without alum ID	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 164 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Phase 1b Study to Evaluate the Safety and Immunogenicity of NDV-3 Formulated With or Without Alum (AlOH) and Administered Either Intramuscular (IM) or Intradermally (ID) to Healthy Adults
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: NDV-3 vaccine with alum IM 300 ug Als3 and 0.5 mg Al as alum in PBS per dose, one dose administered IM	Biological: NDV-3 vaccine with alum IM; One dose administered IM
Active Comparator: NDV-3 vaccine without alum IM 300 ug Als3 in PBS per dose, one dose administered IM	Biological: NDV-3 vaccine without alum IM; One dose administered IM
Placebo Comparator: Placebo IM 0.5 mg Al as alum in PBS per dose, one dose administered IM	Biological: Placebo with alum IM; One dose administered ID
Active Comparator: NDV-3 vaccine without alum ID 30 ug Als3 in PBS per dose, one dose administered ID	Biological: NDV-3 vaccine without alum ID; One dose administered ID

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cetero Research Clinical Site	Fargo	North Dakota	United States	58104

Sponsors and Collaborators

• NovaDigm Therapeutics, Inc.
• United States Department of Defense

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Schmidt CS, White CJ, Ibrahim AS, Filler SG, Fu Y, Yeaman MR, Edwards JE Jr, Hennessey JP Jr. NDV-3, a recombinant alum-adjuvanted vaccine for Candida and Staphylococcus aureus, is safe and immunogenic in healthy adults. Vaccine. 2012 Dec 14;30(52):7594-600. doi: 10.1016/j.vaccine.2012.10.038. Epub 2012 Oct 22.

• Responsible Party: NovaDigm Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01447407
• Other Study ID Numbers: NDV3-002
• First Posted: Oct 6, 2011
• Last Update Posted: Mar 4, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by NovaDigm Therapeutics, Inc.: Staphylococcal infections; Yeast infections; Candidiasis
• Additional relevant MeSH terms: Infections; Communicable Diseases; Candidiasis; Staphylococcal Infections; Vaccines; Aluminum sulfate

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Arm/Group Description	NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM	NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM	Placebo administered ID: One dose saline placebo administered ID	NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID
Period Title: Overall Study
STARTED	41	40	41	42
COMPLETED	39	40	40	40
NOT COMPLETED	2	0	1	2

Baseline Characteristics

Arm/Group Title	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID	Total
Arm/Group Description	NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM	NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM	Placebo administered ID: One dose saline placebo administered ID	NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID	Total of all reporting groups
Overall Participants	41	40	41	42	164
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	31.8	30.1	32.3	31.0	31.3
Sex: Female, Male (Count of Participants)
Female	33 80.5%	33 82.5%	34 82.9%	34 81%	134 81.7%
Male	8 19.5%	7 17.5%	7 17.1%	8 19%	30 18.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	1 2.4%	1 0.6%
Not Hispanic or Latino	41 100%	40 100%	41 100%	41 97.6%	163 99.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 2.5%	1 2.4%	0 0%	2 1.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 2.5%	1 2.4%	2 4.8%	4 2.4%
White	38 92.7%	37 92.5%	36 87.8%	38 90.5%	149 90.9%
More than one race	3 7.3%	1 2.5%	3 7.3%	2 4.8%	9 5.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Arm/Group Description	NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM	NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM	Placebo administered ID: One dose saline placebo administered ID	NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID
Measure Participants	39	40	40	40
>=1 TEAE	35 85.4%	33 82.5%	30 73.2%	36 85.7%
>=1 severe TEAE	2 4.9%	0 0%	4 9.8%	2 4.8%
>=1 severe drug-related TEAE	0 0%	0 0%	0 0%	0 0%
DIscontinued for >=1 TEAE	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Immunogenicity - Serum Anti-Als3 IgG
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Arm/Group Description	NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM	NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM	Placebo administered ID: One dose saline placebo administered ID	NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID
Measure Participants	39	40	40	40
Baseline	372 (3.12)	320 (3.07)	363 (2.93)	375 (3.53)
Day 7	4447 (6.31)	3070 (6.71)	365 (2.81)	874 (5.25)
Day 14	44675 (3.04)	22675 (6.58)	370 (2.89)	5153 (6.97)
Day 28	38898 (2.83)	19220 (6.00)	377 (2.93)	4513 (6.60)
Day 90/Exit	20853 (3.24)	11771 (5.93)	347 (2.71)	3282 (5.55)

3. Secondary Outcome

Title	Immunogenicity - Serum Anti-Als3 IgA1
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Arm/Group Description	NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM	NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM	Placebo administered ID: One dose saline placebo administered ID	NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID
Measure Participants	39	40	40	40
Baseline	573 (4.07)	480 (3.44)	418 (3.72)	550 (4.93)
Day 7	7643 (6.61)	5497 (7.01)	431 (3.69)	1640 (6.56)
Day 14	69616 (3.1)	34946 (6.77)	429 (3.93)	9356 (6014)
Day 28	43790 (2.59)	19999 (5.36)	412 (3.86)	7400 (6.33)
Day 90/Exit	20656 (2.51)	10698 (4.61)	404 (3.78)	3641 (5.18)

4. Secondary Outcome

Title	Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Arm/Group Description	NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM	NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM	Placebo administered ID: One dose saline placebo administered ID	NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID
Measure Participants	39	40	40	40
Baseline	2 (1.5)	2 (1.55)	3 (2.12)	3 (1.98)
Day 7	4 (3.98)	6 (5.84)	2 (1.61)	3 (2.45)
Day 14	78 (7.12)	26 (7.50)	3 (1.99)	8 (4.27)
Day 28	44 (5.85)	26 (7.09)	3 (2.20)	8 (4.63)
Day 90/Exit	20 (4.93)	13 (4.65)	3 (2.11)	6 (4.35)

5. Secondary Outcome

Title	Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Arm/Group Description	NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM	NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM	Placebo administered ID: One dose saline placebo administered ID	NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID
Measure Participants	39	40	40	40
Baseline	3 (2.03)	3 (2.08)	3 (2.24)	3 (2.5)
Day 7	5 (2.87)	7 (6.64)	3 (1.45)	4 (2.71)
Day 14	83 (4.50)	29 (6.48)	3 (1.64)	12 (4.23)
Day 28	36 (3.82)	25 (6.72)	3 (2.40)	8 (4.56)
Day 90/Exit	15 (3.18)	8 (3.27)	3 (1.98)	5 (3.40)

6. Secondary Outcome

Title	Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Arm/Group Description	NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM	NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM	Placebo administered ID: One dose saline placebo administered ID	NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID
Measure Participants	39	40	40	40
Baseline	7 17.1%	9 22.5%	7 17.1%	5 11.9%
Day 7	27 65.9%	25 62.5%	10 24.4%	20 47.6%
Day 14	19 46.3%	21 52.5%	5 12.2%	20 47.6%
Day 90/Exit	25 61%	18 45%	9 22%	14 33.3%

7. Secondary Outcome

Title	Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Arm/Group Description	NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM	NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM	Placebo administered ID: One dose saline placebo administered ID	NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID
Measure Participants	39	40	40	40
Baseline	6 14.6%	10 25%	12 29.3%	9 21.4%
Day 7	22 53.7%	19 47.5%	8 19.5%	13 31%
Day 14	15 36.6%	17 42.5%	7 17.1%	16 38.1%
Day 90/Exit	17 41.5%	15 37.5%	18 43.9%	23 54.8%

Adverse Events

Time Frame	90 days
Arm/Group Title	NDV-3 Vaccine With Alum		NDV-3 Vaccine Without Alum		Placebo		NDV-3 Vaccine ID
Arm/Group Description	NDV-3 (300 ug Als3) vaccine with alum administered IM: One dose administered IM		NDV-3 (300 ug Als3) vaccine without alum administered IM: One dose administered IM		Placebo administered ID: One dose saline placebo administered ID		NDV-3 (30 ug Als3) vaccine without alum administered ID: One dose administered ID
All Cause Mortality
	NDV-3 Vaccine With Alum		NDV-3 Vaccine Without Alum		Placebo		NDV-3 Vaccine ID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/42 (0%)
Serious Adverse Events
	NDV-3 Vaccine With Alum		NDV-3 Vaccine Without Alum		Placebo		NDV-3 Vaccine ID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/40 (0%)		0/41 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	NDV-3 Vaccine With Alum		NDV-3 Vaccine Without Alum		Placebo		NDV-3 Vaccine ID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/41 (85.4%)		33/40 (82.5%)		30/41 (73.2%)		36/42 (85.7%)
Gastrointestinal disorders
Diarrhoea	2/41 (4.9%)	2	2/40 (5%)	2	3/41 (7.3%)	3	3/42 (7.1%)	3
Nausea	5/41 (12.2%)	5	2/40 (5%)	2	1/41 (2.4%)	1	7/42 (16.7%)	7
General disorders
Fatigue	4/41 (9.8%)	4	4/40 (10%)	4	4/41 (9.8%)	4	13/42 (31%)	13
Injection site erythema	1/41 (2.4%)	1	1/40 (2.5%)	1	0/41 (0%)	0	8/42 (19%)	8
Injection site pain	32/41 (78%)	32	18/40 (45%)	18	3/41 (7.3%)	3	15/42 (35.7%)	15
Injection site pruritus	1/41 (2.4%)	1	1/40 (2.5%)	1	0/41 (0%)	0	8/42 (19%)	8
Injection site swelling	1/41 (2.4%)	1	2/40 (5%)	2	0/41 (0%)	0	1/42 (2.4%)	1
Infections and infestations
Nasopharyngitis	3/41 (7.3%)	3	4/40 (10%)	4	1/41 (2.4%)	1	0/42 (0%)	0
Injury, poisoning and procedural complications
Procedural dizziness	0/41 (0%)	0	1/40 (2.5%)	1	1/41 (2.4%)	1	3/42 (7.1%)	3
Investigations
Alanine aminotransferase increased	1/41 (2.4%)	1	2/40 (5%)	2	3/41 (7.3%)	3	1/42 (2.4%)	1
Blood albumin decreased	0/41 (0%)	0	2/40 (5%)	2	1/41 (2.4%)	1	0/42 (0%)	0
Blood glucose increased	3/41 (7.3%)	3	1/40 (2.5%)	1	5/41 (12.2%)	5	6/42 (14.3%)	6
Protein total decreased	2/41 (4.9%)	2	8/40 (20%)	8	3/41 (7.3%)	3	7/42 (16.7%)	7
Protein urine present	4/41 (9.8%)	4	0/40 (0%)	0	4/41 (9.8%)	4	4/42 (9.5%)	4
Red blood cells urine positive	5/41 (12.2%)	5	7/40 (17.5%)	7	9/41 (22%)	9	7/42 (16.7%)	7
Musculoskeletal and connective tissue disorders
Myalgia	1/41 (2.4%)	1	1/40 (2.5%)	1	1/41 (2.4%)	1	8/42 (19%)	8
Nervous system disorders
Headache	10/41 (24.4%)	10	7/40 (17.5%)	7	9/41 (22%)	9	19/42 (45.2%)	19
Respiratory, thoracic and mediastinal disorders
Nasal congestion	1/41 (2.4%)	1	1/40 (2.5%)	1	3/41 (7.3%)	3	3/42 (7.1%)	3
Oropharyngeal pain	2/41 (4.9%)	2	4/40 (10%)	4	2/41 (4.9%)	2	2/42 (4.8%)	2
Rhinorrhoea	2/41 (4.9%)	2	2/40 (5%)	2	1/41 (2.4%)	1	3/42 (7.1%)	3
Sinus congestion	1/41 (2.4%)	1	2/40 (5%)	2	1/41 (2.4%)	1	3/42 (7.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.