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| ID | Type | Description | Link |
|---|---|---|---|
| A-18716 | Other Identifier | Walter Reed Army Institute of Research | |
| NMRC.2015.0003 | Other Identifier | Naval Medical Research Center |
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This study is an open-label, dose-escalating Phase 1 investigation of S. flexneri 2a InvaplexAR vaccine. A total of up to 40 subjects will receive one of four S. flexneri 2a InvaplexAR vaccine doses. The vaccine will be administered intranasally (without adjuvant).
The vaccine will be administered on Days 0,14, and 28. Volunteers (10 per group [8 minimum]) will receive the same dose at each vaccination dependent upon group assignment. Groups will be divided according to the table below. An interval no less than 1 week will separate the third dose of a group from the first dose of the next group (receiving an increased InvaplexAR dose). Blood, stool, and saliva specimens will be collected at pre-specified intervals to examine systemic and mucosal vaccine antigen-specific immune responses. Ocular tear samples will be collected in groups C and D. Vaccine safety will be actively monitored during vaccination and for 28 days following the third vaccine dose. The decision to advance to the next dose level is based on the safety assessment (not immunogenicity). A dose level with no occurrence of stopping criteria in the 7 days following the last vaccine dose will prompt moving to the next higher level. All safety data will be summarized and reviewed with the research monitor prior to dose escalation. In addition, a report of all safety data will be provided to the sponsor's safety office for informational purposes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 10 μg S. flexneri 2a Invaplex | Active Comparator | 10 subjects vaccinated on days 0, 14, 28 |
|
| 50 μg S. flexneri 2a Invaplex | Active Comparator | 10 subjects vaccinated on days 0, 14, 28 |
|
| 250 μg S. flexneri 2a Invaplex | Active Comparator | 10 subjects vaccinated on days 0, 14, 28 |
|
| 500 μg S. flexneri 2a Invaplex | Active Comparator | 10 subjects vaccinated on days 0, 14, 28 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Shigella flexneri 2a InvaplexAR | Biological | The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Treatment Related Adverse Events | Number of adverse events related to the vaccine for each arm | 166 days |
| Antibody Titers Against IgG and IgA Immunizing Antigens | Serum samples will be assayed for antibody titers against the immunizing antigens LPS, IpaB, IpaC, and S. flexneri 2a Invaplex at screening, and Days 0, 14, 28, 35, 42, and 56 for 36 subjects. Previously established high-titer specimens will be included on each plate to track day to day interassay variation. For each antigen, pre- and post-vaccination serum samples will be assayed side-by-side. The antibody titer assigned to each sample will represent the geometric mean of duplicate tests performed on 2 different days. Reciprocal endpoint titers < 5 will be assigned a value of 2.5 for computational purposes. Seroconversion will be defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples AND a post-vaccination reciprocal titer >10. | At screening and Days 0, 14, 28, 35, 42, and 56 |
| Measure | Description | Time Frame |
|---|---|---|
| IgG and IgA Antigen-Specific Antibody Secreting Cell (ASC) Mucosal Responses | ASC responses were assessed using isolated peripheral blood mononuclear cells (PBMCs). For each antigen, pre- and post-vaccination samples were tested on the same plates for total and vaccine-specific numbers. The ASC responses indirectly reflect intestinal immune responses through measurement of antigen-specific B-lymphocytes in systemic circulation before homing to gut effector sites. An ASC response was defined as > 10 ASCs above baseline. |
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Inclusion Criteria:
Exclusion Criteria:
Research specific
Prior Exposure to Shigella
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Duplessis, MD, MPH, MS | Enteric Diseases Department Naval Medical Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Walter Reed Army Institute of Research, Clinical Trials Center | Silver Spring | Maryland | 20910 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37666695 | Derived | Duplessis C, Clarkson KA, Ross Turbyfill K, Alcala AN, Gutierrez R, Riddle MS, Lee T, Paolino K, Weerts HP, Lynen A, Oaks EV, Porter CK, Kaminski R. GMP manufacture of Shigella flexneri 2a Artificial Invaplex (InvaplexAR) and evaluation in a Phase 1 Open-label, dose escalating study administered intranasally to healthy, adult volunteers. Vaccine. 2023 Oct 6;41(42):6261-6271. doi: 10.1016/j.vaccine.2023.08.051. Epub 2023 Sep 2. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 10 μg S. Flexneri 2a Invaplex | 9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
| FG001 | 50 μg S. Flexneri 2a Invaplex | 9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
| FG002 | 250 μg S. Flexneri 2a Invaplex | 10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
| FG003 | 500 μg S. Flexneri 2a Invaplex | 10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 10 μg S. Flexneri 2a Invaplex | 9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Treatment Related Adverse Events | Number of adverse events related to the vaccine for each arm | Posted | Number | Adverse Events | 166 days |
|
Through study completion, an average of 8 months
Vaccine-related (possibly, probably, definitely) surveyed signs and symptoms of all study subjects receiving at least one dose of investigational product was assessed through targeted physical exams, symptom surveys, and other adverse events (AE) monitoring. Subjects were observed in clinic for 30 minutes, 24 hours, and 7days post vaccination to review their symptom diaries and to report any AEs. All vaccine-related and unrelated (not related, unlikely) AEs were reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 10 μg S. Flexneri 2a Invaplex | 9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| AST Elevation | Investigations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christopher Duplessis, MD | Walter Reed Army Institute of Research (WRAIR) Clinical Trials Center (CTC) | 301-319-9047 | Christopher.a.duplessis.mil@mail.mil |
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| ID | Term |
|---|---|
| D004405 | Dysentery, Bacillary |
| ID | Term |
|---|---|
| D004756 | Enterobacteriaceae Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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|
| 56 Days |
| IgG and IgA Antigen-Specific Antibody Lymphocyte Supernatant (ALS) Mucosal Responses | ALS responses were assessed using isolated peripheral blood mononuclear cells (PBMCs). For each antigen, pre- and post-vaccination samples were tested on the same plates for total and vaccine-specific numbers. The ALS responses indirectly reflect intestinal immune responses through measurement of antigen-specific B-lymphocytes in systemic circulation before homing to gut effector sites. An ALS response was defined as a ≥ 4-fold increase over baseline ALS titers. | 56 Days |
| Change in employment |
|
| Symptoms post-vaccination |
|
| BG001 | 50 μg S. Flexneri 2a Invaplex | 9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
| BG002 | 250 μg S. Flexneri 2a Invaplex | 10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
| BG003 | 500 μg S. Flexneri 2a Invaplex | 10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | 250 μg S. Flexneri 2a Invaplex | 10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
| OG003 | 500 μg S. Flexneri 2a Invaplex | 10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. |
|
|
| Primary | Antibody Titers Against IgG and IgA Immunizing Antigens | Serum samples will be assayed for antibody titers against the immunizing antigens LPS, IpaB, IpaC, and S. flexneri 2a Invaplex at screening, and Days 0, 14, 28, 35, 42, and 56 for 36 subjects. Previously established high-titer specimens will be included on each plate to track day to day interassay variation. For each antigen, pre- and post-vaccination serum samples will be assayed side-by-side. The antibody titer assigned to each sample will represent the geometric mean of duplicate tests performed on 2 different days. Reciprocal endpoint titers < 5 will be assigned a value of 2.5 for computational purposes. Seroconversion will be defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples AND a post-vaccination reciprocal titer >10. | Subjects who received at least 2 vaccine doses were included in the immunology analyses. | Posted | Geometric Mean | 95% Confidence Interval | titers | At screening and Days 0, 14, 28, 35, 42, and 56 |
|
|
|
| Secondary | IgG and IgA Antigen-Specific Antibody Secreting Cell (ASC) Mucosal Responses | ASC responses were assessed using isolated peripheral blood mononuclear cells (PBMCs). For each antigen, pre- and post-vaccination samples were tested on the same plates for total and vaccine-specific numbers. The ASC responses indirectly reflect intestinal immune responses through measurement of antigen-specific B-lymphocytes in systemic circulation before homing to gut effector sites. An ASC response was defined as > 10 ASCs above baseline. | Arm 1: One patient was lost to follow-up post dose 1 vaccination, overall participants is therefore 8 for this arm Arm 3: One patient withdrew from the study due to symptoms post dose 1 vaccination, overall participants is therefore 9 for this arm | Posted | Median | 95% Confidence Interval | ASC per 10^6 PBMCs | 56 Days |
|
|
|
| Secondary | IgG and IgA Antigen-Specific Antibody Lymphocyte Supernatant (ALS) Mucosal Responses | ALS responses were assessed using isolated peripheral blood mononuclear cells (PBMCs). For each antigen, pre- and post-vaccination samples were tested on the same plates for total and vaccine-specific numbers. The ALS responses indirectly reflect intestinal immune responses through measurement of antigen-specific B-lymphocytes in systemic circulation before homing to gut effector sites. An ALS response was defined as a ≥ 4-fold increase over baseline ALS titers. | Arm 1: One patient was lost to follow-up post dose 1 vaccination, overall participants is therefore 8 for this arm Arm 3: One patient withdrew from the study due to symptoms post dose 1 vaccination, overall participants is therefore 9 for this arm | Posted | Median | 95% Confidence Interval | fold change | 56 Days |
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| 9 |
| 9 |
| EG001 | 50 μg S. Flexneri 2a Invaplex | 9 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. | 0 | 9 | 0 | 9 | 9 | 9 |
| EG002 | 250 μg S. Flexneri 2a Invaplex | 10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. | 0 | 10 | 0 | 10 | 10 | 10 |
| EG003 | 500 μg S. Flexneri 2a Invaplex | 10 subjects vaccinated on days 0, 14, 28 Shigella flexneri 2a InvaplexAR: The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot. | 0 | 10 | 0 | 10 | 10 | 10 |
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
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| Fever | General disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Itchy Eyes | Eye disorders | Systematic Assessment |
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| Leukocytosis | Blood and lymphatic system disorders | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Nasal Burning | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal Itching | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal Mucosal Hyperemia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal Pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal Stuffiness | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nasal Tenderness | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | Systematic Assessment |
|
| Post-Nasal Drip | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pulmonary Irritation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sinus Pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Tearing Eyes | Eye disorders | Systematic Assessment |
|
| Upper Respiratory Infection (URI) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Abdominal Cramps | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal Discomfort | Gastrointestinal disorders | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | Systematic Assessment |
|
| BUN Elevation | Investigations | Systematic Assessment |
|
| Chest Tightness (Unknown Etiology) | General disorders | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
|
| Dry Chapped Lips | Gastrointestinal disorders | Systematic Assessment |
|
| Hemoglobinemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Joint Aches (Left Knee and Left Elbow) | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Lightheadedness | Nervous system disorders | Systematic Assessment |
|
| Loose Stools | Gastrointestinal disorders | Systematic Assessment |
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| Low Hemoglobin | Investigations | Systematic Assessment |
|
| Lymphocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Nasal Ulcer | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Olecranon bursitis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Right Hip Tendonitis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Right Knee Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Right Upper Lip Fever Blister | Infections and infestations | Systematic Assessment |
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| Sinusitis | Infections and infestations | Systematic Assessment |
|
| Systolic Hypertension | Vascular disorders | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | Systematic Assessment |
|
| Urinary Tract Infection (UTI) | Infections and infestations | Systematic Assessment |
|
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| D007239 | Infections |
| D004403 | Dysentery |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
| Serum IgA (Invaplex) |
|
| Serum IgG (LPS) |
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| Serum IgA (LPS) |
|
| Serum IgG (IpaB) |
|
| Serum IgA (IpaB) |
|
| Serum IgG (IpaC) |
|
| Serum IgA (IpaC) |
|
| ASC IgA (Invaplex) |
|
| ASC IgG (LPS) |
|
| ASC IgA (LPS) |
|
| ALS IgA (Invaplex) |
|
| ALS IgG (LPS) |
|
| ALS IgA (LPS) |
|