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Due to futility, identified after 5 subjects completed treatment in Part B
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| Name | Class |
|---|---|
| Immune Tolerance Network (ITN) | NETWORK |
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The purpose of this study is to test the oral tolerance of Keyhole Limpet Hemocyanin (KLH) and to determine if Immucothel by itself is strong enough to trigger the immune response. If not, Immucothel will be tested in combination with an adjuvant to determine if an adequate immune response can be seen.
One type of normal immune response is called "oral tolerance." This is when the immune system (the body's natural defense system against illness) turns off (e.g. does not respond) to foods or to other proteins that are eaten. Oral tolerance test is done by feeding people a protein and then vaccinating them with the same protein. Oral tolerance occurs if the vaccination does not cause an immune response.
In this study, oral tolerance of Keyhole Limpet Hemocyanin (KLH) will be tested. KLH is a large protein extracted from a mollusk (a sea animal). The 'native KLH' (which is a large version of this protein) formulation will be used for oral feeding. Immucothel (a smaller version of the KLH protein) will be used for vaccination (injection). Immucothel is an investigational vaccine currently used to treat bladder cancers outside of the US.
Since these particular KLH products have never been used in oral tolerance studies, the investigators want to make sure in this pilot study that they will work as expected in healthy participants before studying these two products in patients with auto-immune disorders.
This study will also determine if Immucothel by itself is strong enough to trigger the immune response. If not, Immucothel will be tested in combination with an adjuvant (a substance that can increase the immune response to a protein like KLH) to determine if an adequate immune response can be seen.
This study consists of two parts. Participants will participate for either 39 days (Part A) or 65 days (Part B). Regardless of the group assignment, a safety follow-up phone call will occur 6 months after the last immunization (189 day for Part A or 215 day for part B) to assess the late onset of adverse events.
Part A of the study will test the experimental vaccine Immucothel by itself or in combination with an adjuvant. Immucothel is a purified protein from a mollusk. Immucothel can be given as a sub-q injection (under the skin) alone or with an adjuvant (a small amount of mineral oil) to help to enhance the immune response. There maybe two groups in this part:
Part B of the study will test the successful Immucothel regimen from Part A with oral KLH. Ten new evaluable (as defined by protocol) participants will be given the experimental oral KLH.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Immucothel alone (Part A) | Experimental | 100 µg Immucothel subcutaneously (SQ) on Day 0 and Day 9. |
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| Immucothel+Montanide (Part A) | Experimental | If an immune response was not observed in at least nine out of the first 10 participants after receiving Immucothel alone, 10 additional healthy subjects would be recruited and immunized with Immucothel (SQ) plus Montanide (SQ) on Day 0 and Day 9. |
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| Immucothel alone or Immucothel+Montanide (Part B) | Experimental | Dependent on the results for Part A. Briefly: Ten new, healthy participants were to be fed 50 mg of native keyhole limpet hemocyanin (KLH), a protein extracted from a mollusk (a sea animal), on Days 0 through 4 and Days 10 through 14, for a total dose of 500 mg. The participants were then immunized using the strategy that produced an immune response in at least nine out of 10 participants in Part A (Immucothel alone or Immucothel plus Montanide) on Days 26 and 35. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immucothel Alone (Part A) | Biological | 100 ug at day 0 (priming dose) and day 9(booster dose) |
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| Measure | Description | Time Frame |
|---|---|---|
| Participants With a Positive Immune Response to T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A) | T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro keyhole limpet hemocyanin (KLH) stimulation of peripheral blood mononuclear cells (PBMC). An SI ≥3 on day 16 will indicate the presence of immune response. The SI is the ratio of 3H-thymidine incorporation by T cells in the presence of KLH stimulation to 3H-thymidine incorporation by T cells in the absence of stimulation. Higher values correspond with lower tolerance to KLH. | Day 16 |
| Participants Demonstrating Tolerance to KLH Using T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part B) | T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro keyhole limpet hemocyanin (KLH) stimulation of peripheral blood mononuclear cells (PBMC). An SI <3 on Day 32 indicated tolerance to KLH. The SI is the ratio of 3H-thymidine incorporation by T cells in the presence of KLH stimulation to 3H-thymidine incorporation by T cells in the absence of stimulation. Higher values correspond with lower tolerance to KLH. | Day 32 |
| T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A) | No data available for analyses | Day 9 |
| T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A) | No data available for analyses. | Day 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Cytokine Secretion Profile of T Cells Stimulated by KLH (Part A) | No data available for analyses. | Days 0, 9, 16 |
| T Cell Stimulation Index Measured by Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) Staining After KLH Stimulation (Part A) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lloyd Mayer, MD | Icahn School of Medicine at Mount Sinai | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mount Sinai Medical Center | New York | New York | 10029 | United States |
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| Label | URL |
|---|---|
| National Institute of Allergy and Infectious DiseasesDivision of Allergy, Immunology, and Transplantation (DAIT) | View source |
| National Institute of Allergy and Infectious Diseases | View source |
| Immune Tolerance Network (ITN) |
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The accrual objective was 10 to 20 evaluable participants in Part A and 10 evaluable participants in Part B. The definition of an evaluable participant (measured/determined by lymphocyte proliferation assay) was provided in the protocol.
One site in the United States recruited 19 healthy adult male and female participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | Immucothel Alone (Part A) | Subjects received 100 µg Immucothel subcutaneously (SQ) on Day 0 and Day 9. If at least nine of the subjects demonstrated an immune response, Part A of the study would be complete. |
| FG001 | Immucothel + Montanide (Part A) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Immucothel+Montanide (Part A) | Biological | 100 ug SQ Immucothel plus Montanide at day 0 (priming dose) and day 9 (booster dose) |
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| Immucothel Alone or Immucothel+Montanide (Part B) | Biological | 50 mg of native KLH on days 0-4 and 10-14 (total of 500 mg). Immunization on days 26 and 35. |
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No data available for analyses.
| Days 0, 9, 16 |
| Suppression (or Non-activation) of Cytokine Secretion Profile of T Cells Stimulated by KLH Following Oral Feeding (Part B) | No data available for analyses. | Day 42 |
| Suppression (or Non-activation) of T Cell Stimulation Index Measured by CFSE Staining After KLH Stimulation (Part B) | No data available for analyses. | Day 42 |
| Other Mechanistic Assessments on Archived Serum Samples Like Anti-KLH Antibodies and Secreted Cytokines (Part B) | No data available for analyses. | 6 months |
| Compare the Level of KLH-specific Antibodies in the Serum (Samples From Various Time Points) Between Parts A and B | No data available for analyses. | 6 months |
| View source |
If an immune response was not observed in at least nine of the subjects after receiving Immucothel alone, 10 additional healthy subjects would be recruited and immunized with Immucothel (SQ) plus Montanide (SQ) on Day 0 and Day 9. If at least nine of the subjects had an immune response after receiving Immucothel plus Montanide, Part A of the study would be completed. |
| FG002 | Immucothel Alone or Immucothel + Montanide (Part B) | Ten new, healthy participants ingested 50 mg of native keyhole limpet hemocyanin (KLH) orally. KLH, a protein extracted from a mollusk (a sea animal), was ingested on Days 0 through 4 and Days 10 through 14, for a total dose of 500 mg. The participants were then immunized using the strategy that produced an immune response in at least nine out of 10 participants in Part A (Immucothel alone or Immucothel plus Montanide) on Days 26 and 35. |
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| NOT COMPLETED |
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Enrolled Sample
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| ID | Title | Description |
|---|---|---|
| BG000 | Immucothel Alone (Part A) | Subjects received 100 µg Immucothel subcutaneously (SQ) on Day 0 and Day 9. If at least nine of the subjects demonstrated an immune response, Part A of the study would be complete. |
| BG001 | Immucothel Alone or Immucothel + Montanide (Part B) | Ten new, healthy participants ingested 50 mg of native keyhole limpet hemocyanin (KLH) orally. KLH, a protein extracted from a mollusk (a sea animal), was ingested on Days 0 through 4 and Days 10 through 14, for a total dose of 500 mg. The participants were then immunized using the strategy that produced an immune response in at least nine out of 10 participants in Part A (Immucothel alone or Immucothel plus Montanide) on Days 26 and 35. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| 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 | Participants With a Positive Immune Response to T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A) | T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro keyhole limpet hemocyanin (KLH) stimulation of peripheral blood mononuclear cells (PBMC). An SI ≥3 on day 16 will indicate the presence of immune response. The SI is the ratio of 3H-thymidine incorporation by T cells in the presence of KLH stimulation to 3H-thymidine incorporation by T cells in the absence of stimulation. Higher values correspond with lower tolerance to KLH. | Intent-to-treat | Posted | Number | participants | Day 16 |
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| Primary | Participants Demonstrating Tolerance to KLH Using T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part B) | T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro keyhole limpet hemocyanin (KLH) stimulation of peripheral blood mononuclear cells (PBMC). An SI <3 on Day 32 indicated tolerance to KLH. The SI is the ratio of 3H-thymidine incorporation by T cells in the presence of KLH stimulation to 3H-thymidine incorporation by T cells in the absence of stimulation. Higher values correspond with lower tolerance to KLH. | Intent-to-treat | Posted | Number | participants | Day 32 |
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| Primary | T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A) | No data available for analyses | Data were not collected and therefore no analyses could be performed. | Posted | Day 9 |
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| Primary | T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A) | No data available for analyses. | Data were not collected and therefore no analyses could be performed. | Posted | Day 16 |
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| Secondary | Cytokine Secretion Profile of T Cells Stimulated by KLH (Part A) | No data available for analyses. | Data were not collected and therefore no analyses could be performed. | Posted | Days 0, 9, 16 |
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| Secondary | T Cell Stimulation Index Measured by Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) Staining After KLH Stimulation (Part A) | No data available for analyses. | Data were not collected and therefore no analyses could be performed. | Posted | Days 0, 9, 16 |
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| Secondary | Suppression (or Non-activation) of Cytokine Secretion Profile of T Cells Stimulated by KLH Following Oral Feeding (Part B) | No data available for analyses. | Data were not collected and therefore no analyses could be performed. | Posted | Day 42 |
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| Secondary | Suppression (or Non-activation) of T Cell Stimulation Index Measured by CFSE Staining After KLH Stimulation (Part B) | No data available for analyses. | Data were not collected and therefore no analyses could be performed. | Posted | Day 42 |
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| Secondary | Other Mechanistic Assessments on Archived Serum Samples Like Anti-KLH Antibodies and Secreted Cytokines (Part B) | No data available for analyses. | Data were not collected and therefore no analyses could be performed. | Posted | 6 months |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Compare the Level of KLH-specific Antibodies in the Serum (Samples From Various Time Points) Between Parts A and B | No data available for analyses. | Data were not collected and therefore no analyses could be performed. | Posted | 6 months |
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Enrollment through last study visit (up to 6 months after last immunization)
Adverse events reported for all enrolled subjects
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Immucothel Alone (Part A) | Subjects received 100 µg Immucothel subcutaneously (SQ) on Day 0 and Day 9. If at least nine of the subjects demonstrated an immune response, Part A of the study would be complete. | 0 | 13 | 4 | 13 | ||
| EG001 | Immucothel + Montanide (Part A) | If an immune response was not observed in at least nine of the subjects after receiving Immucothel alone, 10 additional healthy subjects would be recruited and immunized with Immucothel (SQ) plus Montanide (SQ) on Day 0 and Day 9. If at least nine of the subjects had an immune response after receiving Immucothel plus Montanide, Part A of the study would be completed. | 0 | 0 | 0 | 0 | ||
| EG002 | Immucothel Alone or Immucothel + Montanide (Part B) | Ten new, healthy participants ingested 50 mg of native keyhole limpet hemocyanin (KLH) orally. KLH, a protein extracted from a mollusk (a sea animal), was ingested on Days 0 through 4 and Days 10 through 14, for a total dose of 500 mg. The participants were then immunized using the strategy that produced an immune response in at least nine out of 10 participants in Part A (Immucothel alone or Immucothel plus Montanide) on Days 26 and 35. | 0 | 6 | 4 | 6 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 14.0 | Systematic Assessment |
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| Gingival infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
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| Basophil count increased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Basophil percentage increased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Eosinophil percentage increased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Haematocrit decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Haematocrit increased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Haemoglobin increased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Mean cell haemoglobin decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Red blood cell count decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Breast reconstruction | Surgical and medical procedures | MedDRA 14.0 | Systematic Assessment |
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Data from 4 of the 5 evaluable subjects in Part B was negative for tolerance to KLH as defined by a stimulation index <3 on day 42 after booster immunization. The study was terminated. Data were not collected and no analyses were performed.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research Operations Program | DAIT/NIAID | 301-594-7669 | DAITClinicalTrialsGov@niaid.nih.gov |
| ID | Term |
|---|---|
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C032808 | keyhole-limpet hemocyanin |
| C477385 | montanide ISA 51 |
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| >=65 years |
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| Male |
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| Immucothel Alone or Immucothel + Montanide (Part B) |
Ten new, healthy participants ingested 50 mg of native keyhole limpet hemocyanin (KLH) orally. KLH, a protein extracted from a mollusk (a sea animal), was ingested on Days 0 through 4 and Days 10 through 14, for a total dose of 500 mg. The participants were then immunized using the strategy that produced an immune response in at least nine out of 10 participants in Part A (Immucothel alone or Immucothel plus Montanide) on Days 26 and 35. |
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