CompletedNCT03404674Updated Jan 6, 2021Results posted

Dose Escalating Study of a Prototype CS6 Subunit Vaccine With a Modified Heat-labile Enterotoxin From Enterotoxigenic Escherichia Coli (ETEC)

A Phase 1 interventional study of CssBA and dmLT in Diarrhea, sponsored by PATH. Completed at 1 site in United States. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-01-06.

Sponsored by PATH · Phase 1, Interventional, and Prevention

Phase: Phase 1
Study type: Interventional
Enrollment: 50
Allocation: Non-randomized
Ages: 18 Years to 45 Years
Sex: All

Study summary

This study will evaluate the safety of a prototype Coli surface antigen 6 (CS6) subunit vaccine (CssBA) alone or in combination with Escherichia coli double mutant heat labile toxin (dmLT) given by intramuscular (IM) injection.

Read the detailed description

This is an open-label clinical trial in which a total of 50 participants will receive three injections of either CssBA alone, dmLT alone or CssBA + dmLT. The vaccine will be administered via IM injection to alternating deltoid regions on days 1, 22, and 43. Each participant will receive the same dose at each vaccination dependent upon group assignment. Group A is considered a pilot group in which all 3 doses will be administered and participants monitored for safety 7 days after the third vaccination, prior to the enrollment of participants in Group B.

Conditions studied

Diarrhea

Browse trials for

Keywords

ETEC
Escherichia coli
enteric

Who can participate

Ages eligible: 18 Years to 45 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
Completion and review of comprehension test (achieved > 70% accuracy).
Signed informed consent document.
Available for the required follow-up period and scheduled clinic visits.
Women: Negative pregnancy test with understanding (through informed consent process) to not become pregnant during the study or within three (3) months following last vaccination.

Exclusion criteria

Exclusion Criteria:

Health problems (for example, intercurrent febrile illness, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension or any other condition that might place the subject at increased risk of adverse events) - study clinicians, in consultation with the PI, will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the Research Monitor as appropriate.
Clinically significant abnormalities on physical examination.
Immunosuppressive drugs (use of systemic corticosteroids or chemotherapeutics that may influence antibody development) or illness (including immunoglobulin A [IgA] deficiency, defined by serum IgA \< 7 mg/dL).
Women who are pregnant or planning to become pregnant during the study period plus three (3) months beyond the last received dose and currently nursing women.
Participation in research involving another investigational product (defined as receipt of investigational product or exposure to invasive investigational device) 30 days before planned date of first vaccination or anytime through the last study safety visit.
Positive blood test for Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1/2.
Clinically significant abnormalities on basic laboratory screening.
Exclusionary skin disease history/findings that would confound assessment or prevent appropriate local monitoring of adverse events (AEs), or possibly increase the risk of a local AE
History of chronic skin disease (clinician judgement)
Acute skin infection/eruptions on the upper arms including fungal infections, severe acne or active contact dermatitis
Allergies that may increase the risk of AEs
Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid therapy
Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on a regular basis; loose or liquid stools on other than an occasional basis
History of microbiologically confirmed ETEC or cholera infection in the last 3 years
Travel to countries where ETEC or V. cholerae or other enteric infections are endemic (most of the developing world) within 3 years prior to dosing (clinician judgement)
Symptoms consistent with Travelers' Diarrhea or concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within 3 years prior to dosing, OR planned travel to endemic countries during the length of the study
Vaccination for or ingestion of ETEC, cholera, or E. coli heat labile toxin within 3 years prior to dosing
Occupation involving handling of ETEC or V. cholerae currently, or in the past 3 years

Study design

Phase: Phase 1
Primary purpose: Prevention
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 50 participants (actual)

Study arms

Experimental
Group A1: CssBA 5 ug
Participants received an intramuscular injection of 5 ug CssBA on days 1, 22, and 43.
Biological: CssBA
Experimental
Group A2: DmLT 100 ng
Participants received an intramuscular injection of 100 ng DmLT on days 1, 22, and 43.
Biological: dmLT
Experimental
Group B: CssBA 5 ug + DmLT 100 ng
Participants received an intramuscular injection of 5 ug CssBA + 100 ng dmLT on days 1, 22, and 43.
Biological: CssBA · Biological: dmLT
Experimental
Group C: CssBA 5 ug + DmLT 500 ng
Participants received an intramuscular injection of 5 ug CssBA + 500 ng dmLT on days 1, 22, and 43.
Biological: CssBA · Biological: dmLT
Experimental
Group D: CssBA 15 ug + DmLT 500 ng
Participants received an intramuscular injection of 15 ug CssBA + 500 ng dmLT on days 1, 22, and 43.
Biological: CssBA · Biological: dmLT
Experimental
Group E: CssBA 45 ug + DmLT 500 ng
Participants received an intramuscular injection of 45 ug CssBA + 500 ng dmLT on days 1, 22, and 43.
Biological: CssBA · Biological: dmLT

Interventions

BiologicalCssBA
Recombinant enterotoxigenic Escherichia coli (ETEC) surface antigen 6 containing modified structural subunits A and B
Also known as: spd_dsc16Bntd14CssBAB7A[His]₆
BiologicaldmLT
Escherichia coli double mutant heat-labile toxin with mutations at amino acids 192 and 211

What researchers measure

Primary outcomes

Number of Participants With Solicited Adverse Events
Solicited adverse events included vaccine site pain, vaccine site pruritus, vaccine site rash/eruption, vaccine site swelling, vaccine site tenderness, fever, headache, diarrhea, arthralgia, myalgia, malaise, nausea, and vomiting. Adverse events were assessed for severity by the investigator according to the following: Mild (Grade 1): Does not interfere with routine activities, minimal level of discomfort Moderate (Grade 2): Interferes with routine activities, moderate level of discomfort Severe (Grade 3): Unable to perform routine activities, significant level of discomfort Potentially life-threatening (Grade 4): Hospitalization or emergency room (ER) visit for potentially life-threatening event
Time frame: From first vaccination to 28 days after the third vaccination, 71 days.
Number of Participants With Unsolicited Adverse Events
Adverse events were assessed for severity by the investigator according to the following: Mild (Grade 1): Does not interfere with routine activities Minimal level of discomfort Moderate (Grade 2): Interferes with routine activities Moderate level of discomfort Severe (Grade 3): Unable to perform routine activities Significant level of discomfort Potentially life-threatening (Grade 4): Hospitalization or emergency room (ER) visit for potentially life-threatening event
Time frame: From first vaccination to 28 days after the third vaccination, 71 days.

Secondary outcomes

Percentage of Participants With a Serum Immunologic Response to Coli Surface Antigen 6 (CS6)
Serum samples were assayed for immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody titers against CS6 using an enzyme-linked Immunosorbent assay (ELISA). Immunologic response was defined as a ≥ 4-fold increase in reciprocal endpoint titer between Baseline and any post-vaccination sample.
Time frame: Baseline (Day 1 predose), Days 22 and 43 predose, and Day 70
Percentage of Participants With a Serum Immunologic Response to Labile Toxin
Serum samples were assayed for immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody titers against labile toxin using an enzyme-linked Immunosorbent assay (ELISA). Immunologic response was defined as a ≥ 4-fold increase in reciprocal endpoint titer between Baseline and any post-vaccination sample.
Time frame: Baseline (Day 1 predose), Days 22 and 43 predose, and Day 70
Percentage of Participants With a Mucosal Immunologic Response to Coli Surface Antigen 6 (CS6)
Peripheral blood mononuclear cells (PBMCs) were collected to determine antibody responses from lymphocyte supernatant against CS6 at Baseline and 7 days after each vaccination. Antibody in lymphocyte supernatant (ALS) is an indirect quantification of antibody secreting cells (ASC) activated in the mucosa that circulate in the peripheral blood about seven days post-mucosal immunization/infection. After incubation, lymphocyte supernatant was assayed for antigen-specific IgG and IgA antibodies using ELISA. A positive ALS response was defined as a four-fold rise in antibody titers between Baseline and any post vaccination sample.
Time frame: Baseline (Day 1 pre-dose), Days 8 and 29 predose, and Day 50
Percentage of Participants With a Mucosal Immunologic Response to Labile Toxin
Peripheral blood mononuclear cells (PBMCs) were collected to determine antibody responses from lymphocyte supernatant against labile toxin at Baseline and 7 days after each vaccination. Antibody in lymphocyte supernatant (ALS) is an indirect quantification of antibody secreting cells (ASC) activated in the mucosa that circulate in the peripheral blood about seven days post-mucosal immunization/infection. After incubation, lymphocyte supernatant was assayed for antigen-specific IgG and IgA antibodies using ELISA. A positive ALS response was defined as a four-fold rise in antibody titers between Baseline and any post vaccination sample.
Time frame: Baseline (Day 1 pre-dose), Days 8 and 29 predose, and Day 50
Geometric Mean Titer of Serum Anti-CS6 Immunoglobulin G Antibodies
Serum samples were assayed for IgG antibody titers against CS6 using an enzyme-linked Immunosorbent assay (ELISA).
Time frame: Days 1, 22, and 43 pre-vaccination, and Day 70
Geometric Mean Titer of Serum Anti-CS6 Immunoglobulin A Antibodies
Serum samples were assayed for IgA antibody titers against CS6 using an enzyme-linked Immunosorbent assay (ELISA).
Time frame: Days 1, 22, and 43 pre-vaccination, and Day 70
Geometric Mean Titer of Serum Anti-LT Immunoglobulin G Antibodies
Serum samples were assayed for IgG antibody titers against labile toxin using an enzyme-linked Immunosorbent assay (ELISA).
Time frame: Days 1, 22, and 43 pre-vaccination, and Day 70
Geometric Mean Titer of Serum Anti-LT Immunoglobulin A Antibodies
Serum samples were assayed for IgA antibody titers against labile toxin using an enzyme-linked Immunosorbent assay (ELISA).
Time frame: Days 1, 22, and 43 pre-vaccination, and Day 70
Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-CS6 Immunoglobulin G Antibodies
Lymphocyte supernatant was assayed for IgG antibody titers against CS6 using ELISA.
Time frame: Days 1, 8, 29 and 50
Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-CS6 Immunoglobulin A Antibodies
Lymphocyte supernatant was assayed for IgA antibody titers against CS6 using ELISA.
Time frame: Days 1, 8, 29, and 50
Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-LT Immunoglobulin G Antibodies
Lymphocyte supernatant was assayed for IgG antibody titers against labile toxin using ELISA.
Time frame: Days 1, 8, 29, and 50
Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-LT Immunoglobulin A Antibodies
Lymphocyte supernatant was assayed for IgA antibody titers against labile toxin using ELISA.
Time frame: Days 1, 8, 29, and 50

Results

Posted Jan 6, 2021

Participant flow

Healthy adult men and women, civilian and active-duty military, were recruited from the Baltimore/Washington, DC area through the Walter Reed Army Institute of Research (WRAIR) Clinical Trials Center (CTC) by the use of advertisement in multiple media formats.

Participant flow — Overall Study
Milestone	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Started	5	5	10	10	10	10
Received dose 2	5	4	10	9	10	10
Received dose 3	5	4	9	9	10	9
Completed	5	4	8	9	10	9
Not completed	0	1	2	1	0	1
Withdrew: Inability to attend future visits	0	1	1	0	0	0
Withdrew: Behavioral problems	0	0	1	0	0	0
Withdrew: Started a medication that precluded eligibility	0	0	0	1	0	1

Outcome measures

PrimaryNumber of Participants With Solicited Adverse Events

Solicited adverse events included vaccine site pain, vaccine site pruritus, vaccine site rash/eruption, vaccine site swelling, vaccine site tenderness, fever, headache, diarrhea, arthralgia, myalgia, malaise, nausea, and vomiting. Adverse events were assessed for severity by the investigator according to the following: Mild (Grade 1): Does not interfere with routine activities, minimal level of discomfort Moderate (Grade 2): Interferes with routine activities, moderate level of discomfort Severe (Grade 3): Unable to perform routine activities, significant level of discomfort Potentially life-threatening (Grade 4): Hospitalization or emergency room (ER) visit for potentially life-threatening event

Time frame:: From first vaccination to 28 days after the third vaccination, 71 days.
Reported as:: Count of participants · Participants

Number of Participants With Solicited Adverse Events
Participants	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Mild	2	5	9	9	10	10
Moderate	0	0	2	1	2	2
Severe	0	0	0	0	1	0
Life-threatening	0	0	0	0	0	0

SecondaryPercentage of Participants With a Serum Immunologic Response to Coli Surface Antigen 6 (CS6)

Serum samples were assayed for immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody titers against CS6 using an enzyme-linked Immunosorbent assay (ELISA). Immunologic response was defined as a ≥ 4-fold increase in reciprocal endpoint titer between Baseline and any post-vaccination sample.

Time frame:: Baseline (Day 1 predose), Days 22 and 43 predose, and Day 70
Reported as:: Number · percentage of participants

Percentage of Participants With a Serum Immunologic Response to Coli Surface Antigen 6 (CS6)
percentage of participants	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
IgA response	0.0	0.0	0.0	44.4	30.0	50.0
IgG response	20.0	0.0	77.8	100.0	100.0	90.0

SecondaryPercentage of Participants With a Serum Immunologic Response to Labile Toxin

Serum samples were assayed for immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody titers against labile toxin using an enzyme-linked Immunosorbent assay (ELISA). Immunologic response was defined as a ≥ 4-fold increase in reciprocal endpoint titer between Baseline and any post-vaccination sample.

Time frame:: Baseline (Day 1 predose), Days 22 and 43 predose, and Day 70
Reported as:: Number · percentage of participants

Percentage of Participants With a Serum Immunologic Response to Labile Toxin
percentage of participants	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
IgA response	0.0	50.0	22.2	77.8	50.0	70.0
IgG response	0.0	100.0	66.7	100.0	90.0	100.0

SecondaryPercentage of Participants With a Mucosal Immunologic Response to Coli Surface Antigen 6 (CS6)

Peripheral blood mononuclear cells (PBMCs) were collected to determine antibody responses from lymphocyte supernatant against CS6 at Baseline and 7 days after each vaccination. Antibody in lymphocyte supernatant (ALS) is an indirect quantification of antibody secreting cells (ASC) activated in the mucosa that circulate in the peripheral blood about seven days post-mucosal immunization/infection. After incubation, lymphocyte supernatant was assayed for antigen-specific IgG and IgA antibodies using ELISA. A positive ALS response was defined as a four-fold rise in antibody titers between Baseline and any post vaccination sample.

Time frame:: Baseline (Day 1 pre-dose), Days 8 and 29 predose, and Day 50
Reported as:: Number · percentage of participants

Percentage of Participants With a Mucosal Immunologic Response to Coli Surface Antigen 6 (CS6)
percentage of participants	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
IgA response	0.0	0.0	33.3	88.9	80.0	100.0
IgG response	60.0	0.0	100.0	88.9	100.0	80.0

SecondaryPercentage of Participants With a Mucosal Immunologic Response to Labile Toxin

Peripheral blood mononuclear cells (PBMCs) were collected to determine antibody responses from lymphocyte supernatant against labile toxin at Baseline and 7 days after each vaccination. Antibody in lymphocyte supernatant (ALS) is an indirect quantification of antibody secreting cells (ASC) activated in the mucosa that circulate in the peripheral blood about seven days post-mucosal immunization/infection. After incubation, lymphocyte supernatant was assayed for antigen-specific IgG and IgA antibodies using ELISA. A positive ALS response was defined as a four-fold rise in antibody titers between Baseline and any post vaccination sample.

Time frame:: Baseline (Day 1 pre-dose), Days 8 and 29 predose, and Day 50
Reported as:: Number · percentage of participants

Percentage of Participants With a Mucosal Immunologic Response to Labile Toxin
percentage of participants	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
IgA response	0.0	100.0	22.2	77.8	90.0	100.0
IgG response	0.0	100.0	100.0	100.0	100.0	100.0

SecondaryGeometric Mean Titer of Serum Anti-CS6 Immunoglobulin G Antibodies

Serum samples were assayed for IgG antibody titers against CS6 using an enzyme-linked Immunosorbent assay (ELISA).

Time frame:: Days 1, 22, and 43 pre-vaccination, and Day 70
Reported as:: Geometric mean · titer

Geometric Mean Titer of Serum Anti-CS6 Immunoglobulin G Antibodies
titer	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Day 1 (pre-vaccination)	39.0 (18.2 to 83.6)	29.6 (17.5 to 50.1)	39.1 (22.2 to 69.1)	36.9 (20.5 to 66.6)	40.5 (24.6 to 66.7)	51.5 (26.1 to 101.4)
Day 22 (pre-vaccination)	40.2 (17.8 to 90.8)	34.1 (12.9 to 90.7)	28.2 (21.6 to 36.8)	81.2 (16.6 to 396.6)	80.1 (39.4 to 162.9)	107.1 (28.3 to 405.7)
Day 43 (pre-vacination)	57.4 (16.9 to 195)	46.6 (14.5 to 149.8)	108.9 (54.3 to 218.4)	513.5 (77.2 to 3415.4)	288.2 (100.2 to 829.2)	958.3 (235.9 to 3893.4)
Day 70 (28 days after last vaccination)	81.3 (19.0 to 346.7)	29.4 (17.8 to 48.5)	695.3 (182.1 to 2655.3)	4631.2 (1462.3 to 14667.6)	2520.4 (1199.2 to 5297.2)	5167.1 (1298.8 to 20556.8)

SecondaryGeometric Mean Titer of Serum Anti-CS6 Immunoglobulin A Antibodies

Serum samples were assayed for IgA antibody titers against CS6 using an enzyme-linked Immunosorbent assay (ELISA).

Time frame:: Days 1, 22, and 43 pre-vaccination, and Day 70
Reported as:: Geometric mean · titer

Geometric Mean Titer of Serum Anti-CS6 Immunoglobulin A Antibodies
titer	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Day 1 (pre-vaccination)	269.9 (133.6 to 545.1)	213.4 (73.0 to 623.6)	308.5 (181.4 to 524.4)	330.0 (176.1 to 618.6)	368.2 (192.3 to 705.0)	370.8 (180.9 to 760.0)
Day 22 (pre-vaccination)	294.3 (128.7 to 672.9)	215 (64.9 to 712.4)	285.1 (172.9 to 469.9)	846.9 (189.1 to 3792.6)	408.0 (223.1 to 746.1)	523.5 (262.0 to 1045.9)
Day 43 (pre-vacination)	260.9 (122.0 to 557.8)	164.7 (47.5 to 571.3)	328.7 (200.5 to 538.8)	1571.0 (341.7 to 7222.1)	505.2 (275.8 to 925.4)	1188.9 (515.4 to 2742.6)
Day 70 (28 days after last vaccination)	339.1 (143.6 to 800.6)	218.0 (48.4 to 982.4)	521.6 (236.5 to 1150.3)	2483.1 (595.3 to 10357.2)	970.3 (553.4 to 1701.4)	2170.4 (1053.0 to 4473.7)

PrimaryNumber of Participants With Unsolicited Adverse Events

Adverse events were assessed for severity by the investigator according to the following: Mild (Grade 1): Does not interfere with routine activities Minimal level of discomfort Moderate (Grade 2): Interferes with routine activities Moderate level of discomfort Severe (Grade 3): Unable to perform routine activities Significant level of discomfort Potentially life-threatening (Grade 4): Hospitalization or emergency room (ER) visit for potentially life-threatening event

Time frame:: From first vaccination to 28 days after the third vaccination, 71 days.
Reported as:: Count of participants · Participants

Number of Participants With Unsolicited Adverse Events
Participants	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Mild	4	3	5	6	10	9
Moderate	2	0	2	0	1	3
Severe	1	0	1	0	1	2
Life-threatening	0	0	0	0	0	0

SecondaryGeometric Mean Titer of Serum Anti-LT Immunoglobulin G Antibodies

Serum samples were assayed for IgG antibody titers against labile toxin using an enzyme-linked Immunosorbent assay (ELISA).

Time frame:: Days 1, 22, and 43 pre-vaccination, and Day 70
Reported as:: Geometric mean · titer

Geometric Mean Titer of Serum Anti-LT Immunoglobulin G Antibodies
titer	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Day 1 (pre-vaccination)	46.1 (16.4 to 129.7)	25.1 (NA to NA)	84.5 (31.8 to 224.0)	88.9 (54.0 to 146.5)	75.0 (37.4 to 150.4)	48.8 (25.0 to 95.2)
Day 22 (pre-vaccination)	48.3 (15.3 to 152.1)	52.8 (11.4 to 243.9)	172.9 (42.4 to 705.5)	1010.3 (182.9 to 5579.8)	235.0 (64.1 to 860.7)	193.2 (80.0 to 466.6)
Day 43 (pre-vacination)	46.3 (15.8 to 136.0)	303.7 (39.8 to 2316.2)	235.6 (67.5 to 822.0)	2671.0 (754.2 to 9459.1)	679.2 (256.7 to 1797.0)	666.8 (339.7 to 1308.9)
Day 70 (28 days after last vaccination)	55.0 (17.8 to 170.1)	398.1 (91.9 to 1724.3)	424.1 (159.7 to 1126.6)	3114.1 (965.3 to 10046.6)	1116.9 (467.8 to 2666.7)	1086.4 (473.8 to 2491.2)

SecondaryGeometric Mean Titer of Serum Anti-LT Immunoglobulin A Antibodies

Serum samples were assayed for IgA antibody titers against labile toxin using an enzyme-linked Immunosorbent assay (ELISA).

Time frame:: Days 1, 22, and 43 pre-vaccination, and Day 70
Reported as:: Geometric mean · titer

Geometric Mean Titer of Serum Anti-LT Immunoglobulin A Antibodies
titer	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Day 1 (pre-vaccination)	25.1 (NA to NA)	25.1 (NA to NA)	28.4 (21.4 to 37.7)	25.8 (24.2 to 27.6)	28.6 (21.3 to 38.5)	25.1 (NA to NA)
Day 22 (pre-vaccination)	25.1 (NA to NA)	30.4 (16.6 to 55.6)	55.8 (24.6 to 126.5)	258.4 (49.3 to 1352.9)	77.8 (35.3 to 171.3)	134.6 (57.0 to 317.6)
Day 43 (pre-vacination)	25.1 (NA to NA)	46.2 (9.0 to 238.30)	48.5 (22.0 to 107.0)	317.9 (72.8 to 1388.5)	75.9 (33.6 to 171.4)	159.6 (62.8 to 405.3)
Day 70 (28 days after last vaccination)	25.1 (NA to NA)	66.1 (10.6 to 410.1)	51.4 (20.9 to 126.4)	202.1 (43.8 to 932.2)	68.2 (29.9 to 155.6)	121.1 (57.2 to 256.1)

SecondaryGeometric Mean Titer of Antibody Lymphocyte Supernatant Anti-CS6 Immunoglobulin G Antibodies

Lymphocyte supernatant was assayed for IgG antibody titers against CS6 using ELISA.

Time frame:: Days 1, 8, 29 and 50
Reported as:: Geometric mean · titer

Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-CS6 Immunoglobulin G Antibodies
titer	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Day 1 (pre-vaccination)	4.0 (NA to NA)	4.0 (NA to NA)	4.0 (NA to NA)	5.7 (2.5 to 12.8)	4. (NA to NA)	4.0 (NA to NA)
Day 8 (7 days after 1st vaccination)	4.0 (NA to NA)	4.0 (NA to NA)	5.0 (2.9 to 8.6)	14.9 (3.2 to 70.3)	8.5 (2.7 to 26.6)	7.1 (3.0 to 17.0)
Day 29 (7 days after 2nd vacination)	6.0 (2.0 to 18.4)	4.0 (NA to NA)	4.0 (NA to NA)	42.9 (10.7 to 172.0)	29.8 (8.2 to 108.6)	47.4 (12.7 to 176.5)
Day 50 (7 days after 3rd vaccination)	18.1 (3.1 to 106.4)	4.0 (NA to NA)	86.7 (43.1 to 174.4)	356.9 (208.5 to 610.7)	238.3 (115.3 to 492.3)	142.8 (32.2 to 633.2)

SecondaryGeometric Mean Titer of Antibody Lymphocyte Supernatant Anti-CS6 Immunoglobulin A Antibodies

Lymphocyte supernatant was assayed for IgA antibody titers against CS6 using ELISA.

Time frame:: Days 1, 8, 29, and 50
Reported as:: Geometric mean · titer

Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-CS6 Immunoglobulin A Antibodies
titer	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Day 1 (pre-vaccination)	2.5 (NA to NA)	2.5 (NA to NA)	2.5 (NA to NA)	2.5 (NA to NA)	2.5 (NA to NA)	2.5 (2.5 to 2.5)
Day 8 (7 days after 1st vaccination)	2.5 (NA to NA)	2.5 (NA to NA)	2.5 (NA to NA)	7.3 (1.3 to 42.2)	2.5 (NA to NA)	4.5 (1.9 to 10.8)
Day 29 (7 days after 2nd vacination)	2.5 (NA to NA)	2.5 (NA to NA)	2.5 (NA to NA)	17.5 (4.0 to 76.0)	3.3 (1.8 to 6.0)	33.1 (14.7 to 74.3)
Day 50 (7 days after 3rd vaccination)	2.5 (NA to NA)	2.5 (NA to NA)	6.4 (2.1 to 19.6)	46.6 (13.8 to 157.2)	24.1 (8.5 to 68.7)	35.2 (17.4 to 71.0)

SecondaryGeometric Mean Titer of Antibody Lymphocyte Supernatant Anti-LT Immunoglobulin G Antibodies

Lymphocyte supernatant was assayed for IgG antibody titers against labile toxin using ELISA.

Time frame:: Days 1, 8, 29, and 50
Reported as:: Geometric mean · titer

Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-LT Immunoglobulin G Antibodies
titer	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Day 1 (pre-vaccination)	2.5 (NA to NA)	2.5 (NA to NA)	3.5 (1.6 to 7.8)	2.5 (NA to NA)	3.1 (2.0 to 4.8)	2.5 (NA to NA)
Day 8 (7 days after 1st vaccination)	2.5 (NA to NA)	2.5 (NA to NA)	6.6 (1.5 to 29.2)	24.0 (6.0 to 97.0)	47.4 (8.7 to 258.8)	17.6 (5.0 to 61.4)
Day 29 (7 days after 2nd vacination)	2.5 (NA to NA)	13.4 (0.6 to 305.9)	10.0 (2.0 to 49.9)	105.8 (60.7 to 184.3)	80.7 (50.2 to 129.9)	253.5 (116.5 to 551.8)
Day 50 (7 days after 3rd vaccination)	2.5 (NA to NA)	88.1 (48.2 to 161.0)	70.0 (41.5 to 117.9)	138.4 (102.0 to 187.7)	123.3 (100.0 to 152.0)	187.5 (101.9 to 345.0)

SecondaryGeometric Mean Titer of Antibody Lymphocyte Supernatant Anti-LT Immunoglobulin A Antibodies

Lymphocyte supernatant was assayed for IgA antibody titers against labile toxin using ELISA.

Time frame:: Days 1, 8, 29, and 50
Reported as:: Geometric mean · titer

Geometric Mean Titer of Antibody Lymphocyte Supernatant Anti-LT Immunoglobulin A Antibodies
titer	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Day 1 (pre-vaccination)	2.0 (NA to NA)	2.0 (NA to NA)	2.0 (NA to NA)	2.8 (1.3 to 5.9)	2.0 (NA to NA)	2.0 (NA to NA)
Day 8 (7 days after 1st vaccination)	2.0 (NA to NA)	2.0 (NA to NA)	3.0 (1.1 to 8.1)	11.7 (2.9 to 46.9)	12.7 (3.8 to 42.8)	9.0 (2.8 to 28.2)
Day 29 (7 days after 2nd vacination)	2.0 (NA to NA)	9.9 (0.5 to 198.1)	4.1 (1.4 to 12.4)	28.7 (8.8 to 93.9)	19.3 (7.9 to 47.3)	60.5 (44.9 to 81.6)
Day 50 (7 days after 3rd vaccination)	2.0 (NA to NA)	13.3 (1.6 to 107.6)	3.6 (1.4 to 9.5)	24.7 (7.6 to 80.0)	23.6 (8.5 to 65.4)	18.7 (5.8 to 60.5)

Adverse events

Collected over From the day of the first vaccination up to 28 days after the third vaccination, 71 days.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Group A1: CssBA 5 µg	0/5 (0%)	0/5 (0%)	4/5 (80%)
Group A2: DmLT 100 ng	0/5 (0%)	0/5 (0%)	5/5 (100%)
Group B: CssBA 5 µg + DmLT 100 ng	0/10 (0%)	0/10 (0%)	10/10 (100%)
Group C: CssBA 5 µg + DmLT 500 ng	0/10 (0%)	0/10 (0%)	10/10 (100%)
Group D: CssBA 15 µg + DmLT 500 ng	0/10 (0%)	0/10 (0%)	10/10 (100%)
Group E: CssBA 45 µg + DmLT 500 ng	0/10 (0%)	0/10 (0%)	10/10 (100%)

Most frequent other events

Showing 10 of 59

Most frequent other events
Event	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng
Vaccination Site PainGeneral disorders	0/5	1/5	2/10	5/10	9/10	9/10
Vaccination Site ErythemaGeneral disorders	1/5	4/5	7/10	7/10	8/10	8/10
Vaccination Site PruritusGeneral disorders	0/5	0/5	1/10	1/10	7/10	0/10
AnemiaBlood and lymphatic system disorders	3/5	1/5	0/10	0/10	2/10	0/10
Upper Respiratory Tract InfectionInfections and infestations	2/5	0/5	1/10	1/10	2/10	6/10
Vaccination Site IndurationGeneral disorders	0/5	0/5	0/10	6/10	5/10	6/10
HeadacheNervous system disorders	1/5	0/5	6/10	2/10	3/10	2/10
HyperkalemiaMetabolism and nutrition disorders	0/5	0/5	1/10	0/10	3/10	4/10
Systolic HypertensionVascular disorders	2/5	0/5	0/10	0/10	0/10	2/10
MyalgiaMusculoskeletal and connective tissue disorders	1/5	0/5	0/10	1/10	2/10	4/10

Baseline characteristics

All enrolled participants

Age, Continuous
Age, Continuous(years)	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng	Total
Median	32 (30 to 41)	29 (27 to 37)	29.5 (26 to 32)	31.5 (27 to 37)	28 (22 to 38)	29.5 (25 to 33)	30 (26 to 37)

Sex: Female, Male
Sex: Female, Male(Participants)	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng	Total
Female	4	2	5	7	5	7	30
Male	1	3	5	3	5	3	20

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng	Total
Hispanic or Latino	0	2	1	0	2	1	6
Not Hispanic or Latino	5	3	9	10	8	9	44
Unknown or Not Reported	0	0	0	0	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng	Total
Asian	0	0	0	2	0	0	2
Black	4	4	3	5	3	4	23
White	1	1	7	3	7	5	24
Multi-race	0	0	0	0	0	1	1

Region of Enrollment
Region of Enrollment(participants)	Group A1: CssBA 5 µg	Group A2: DmLT 100 ng	Group B: CssBA 5 µg + DmLT 100 ng	Group C: CssBA 5 µg + DmLT 500 ng	Group D: CssBA 15 µg + DmLT 500 ng	Group E: CssBA 45 µg + DmLT 500 ng	Total
United States	5	5	10	10	10	10	10

Study locations

1 site

Walter Reed Army Institute of Research Clinical Trial Center
Silver Spring, Maryland 20910, United States

References and documents

Study documents

Study protocol · Aug 31, 2018
Statistical analysis plan · Feb 25, 2019

Documents are hosted by the registry — open the source record to download them.

Registry details

Key details

Study ID: NCT03404674
Lead sponsor: PATH
Collaborators: Naval Medical Research Center, Walter Reed Army Institute of Research (WRAIR)
Responsible party: Sponsor
First posted: Jan 19, 2018
Start date: Jan 16, 2018
Primary completion: Mar 26, 2019
Completion: Mar 26, 2019
Results posted: Jan 6, 2021
Last update: Jan 6, 2021

Study contacts

Tida K Lee, MD, PhD

principal investigator · Naval Medical Research Center

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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