CompletedNCT01447407Updated Mar 4, 2020Results posted

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

A Phase 1 interventional study of NDV-3 vaccine with alum IM and NDV-3 vaccine without alum IM in Staphylococcal Infections, Yeast Infections and Candidiasis, sponsored by NovaDigm Therapeutics, Inc.. Completed at 1 site in United States. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-03-04.

Sponsored by NovaDigm Therapeutics, Inc. · Phase 1, Interventional, and Prevention

Phase: Phase 1
Study type: Interventional
Enrollment: 164
Allocation: Randomized
Ages: 18 Years to 50 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Staphylococcal Infections
Yeast Infections
Candidiasis

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Keywords

Staphylococcal infections
Yeast infections
Candidiasis

Who can participate

Ages eligible: 18 Years to 50 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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

Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 164 participants (actual)

Study arms

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
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
Placebo comparator
Placebo IM
0.5 mg Al as alum in PBS per dose, one dose administered IM
Biological: Placebo with alum IM
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

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

What researchers measure

Primary outcomes

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

Secondary outcomes

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
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
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
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
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
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

Results

Posted Mar 4, 2020

Participant flow

Participant flow — Overall Study
Milestone	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Started	41	40	41	42
Completed	39	40	40	40
Not completed	2	0	1	2
Withdrew: Withdrawal by subject	2	0	0	1
Withdrew: Physician decision	0	0	1	1

Outcome measures

PrimaryNumber 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
Reported as:: Number · participants

Number of Participants With Treatment Emergent Adverse Events
participants	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
>=1 TEAE	35	33	30	36
>=1 severe TEAE	2	0	4	2
>=1 severe drug-related TEAE	0	0	0	0
DIscontinued for >=1 TEAE	0	0	0	0

SecondaryImmunogenicity - 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
Reported as:: Geometric mean · Titer

Immunogenicity - Serum Anti-Als3 IgG
Titer	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
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

SecondaryImmunogenicity - 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
Reported as:: Geometric mean · Titer

Immunogenicity - Serum Anti-Als3 IgA1
Titer	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
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

SecondaryImmunogenicity - 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
Reported as:: Geometric mean · Titer

Immunogenicity - Cervicovaginal Wash Anti-Als3 IgG
Titer	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
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

SecondaryImmunogenicity - 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
Reported as:: Geometric mean · Titer

Immunogenicity - Cervicovaginal Wash Anti-Als3 IgA1
Titer	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
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

SecondaryImmunogenicity - 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
Reported as:: Count of participants · Participants

Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interferon-gamma (IFN-g)
Participants	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Baseline	7	9	7	5
Day 7	27	25	10	20
Day 14	19	21	5	20
Day 90/Exit	25	18	9	14

SecondaryImmunogenicity - 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
Reported as:: Count of participants · Participants

Immunogenicity - Number of Participants Positive for Peripheral Blood Mononuclear Cells (PBMCs) Producing Als3-specific Interleukin-17A (IL-17A)
Participants	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Baseline	6	10	12	9
Day 7	22	19	8	13
Day 14	15	17	7	16
Day 90/Exit	17	15	18	23

Adverse events

Collected over 90 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
NDV-3 Vaccine With Alum	0/41 (0%)	0/41 (0%)	35/41 (85.4%)
NDV-3 Vaccine Without Alum	0/40 (0%)	0/40 (0%)	33/40 (82.5%)
Placebo	0/41 (0%)	0/41 (0%)	30/41 (73.2%)
NDV-3 Vaccine ID	0/42 (0%)	0/42 (0%)	36/42 (85.7%)

Most frequent other events

Showing 10 of 21

Most frequent other events
Event	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID
Injection site painGeneral disorders	32/41	18/40	3/41	15/42
HeadacheNervous system disorders	10/41	7/40	9/41	19/42
FatigueGeneral disorders	4/41	4/40	4/41	13/42
Red blood cells urine positiveInvestigations	5/41	7/40	9/41	7/42
Protein total decreasedInvestigations	2/41	8/40	3/41	7/42
Injection site erythemaGeneral disorders	1/41	1/40	0/41	8/42
Injection site pruritusGeneral disorders	1/41	1/40	0/41	8/42
MyalgiaMusculoskeletal and connective tissue disorders	1/41	1/40	1/41	8/42
NauseaGastrointestinal disorders	5/41	2/40	1/41	7/42
Blood glucose increasedInvestigations	3/41	1/40	5/41	6/42

Baseline characteristics

Age, Continuous
Age, Continuous(years)	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID	Total
Mean	31.8 (18 to 47)	30.1 (18 to 49)	32.3 (19 to 50)	31.0 (18 to 50)	31.3 (18 to 50)

Sex: Female, Male
Sex: Female, Male(Participants)	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID	Total
Female	33	33	34	34	134
Male	8	7	7	8	30

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID	Total
Hispanic or Latino	0	0	0	1	1
Not Hispanic or Latino	41	40	41	41	163
Unknown or Not Reported	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	NDV-3 Vaccine With Alum	NDV-3 Vaccine Without Alum	Placebo	NDV-3 Vaccine ID	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	0	1	1	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	1	1	2	4
White	38	37	36	38	149
More than one race	3	1	3	2	9
Unknown or Not Reported	0	0	0	0	0

Study locations

1 site

Cetero Research Clinical Site
Fargo, North Dakota 58104, United States

References and documents

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. PubMed 23099329 ↗

Registry details

Key details

Study ID: NCT01447407
Lead sponsor: NovaDigm Therapeutics, Inc.
Collaborators: United States Department of Defense
Responsible party: Sponsor
First posted: Oct 6, 2011
Start date: Sep 2011
Primary completion: Mar 2012
Completion: Dec 2012
Results posted: Mar 4, 2020
Last update: Mar 4, 2020

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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