Pilot Study to Determine the Immunogenicity of Immucothel® and Oral Tolerance Induction With Biosyn Native KLH in Healthy Subjects (ITN047AI)
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- 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)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ability to give informed consent and comply with study procedures.
- •Participant able/willing to hold off receiving prophylactic immunizations (like influenza or pneumococcal vaccines) during the study period.
排除标准
- •Use of corticosteroids within 2 weeks prior to screening visit.
- •First degree relative (parent, sibling or child) with history of autoimmune disease.
- •Presence of chronic medical illness including but not limited to chronic kidney-, liver-, cardio-vascular diseases, immunodeficiencies, anemia, B12 deficiency, malignancies, or chronic active infections.
- •History of acute gastrointestinal illness within 2 weeks prior to oral KLH administration.
- •For women of child bearing age, participant unwilling to defer pregnancy, has a positive urine pregnancy test or is currently pregnant or lactating.
- •Use of an investigational drug within 3 months of the screening visit.
- •History of acute febrile illness within 1 week of screening visit.
- •History of allergy to shellfish, previous exposure to KLH/product containing KLH or known-sensitivity to KLH / components of KLH preparation.
- •Participants receiving any immunizations within 1 month prior to screening visit.
结局指标
主要结局
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)
时间窗: Day 16
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.
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)
时间窗: Day 32
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.
T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A)
时间窗: Day 16
No data available for analyses.
次要结局
- Suppression (or Non-activation) of Cytokine Secretion Profile of T Cells Stimulated by KLH Following Oral Feeding (Part B)(Day 42)
- Cytokine Secretion Profile of T Cells Stimulated by KLH (Part A)(Days 0, 9, 16)
- T Cell Stimulation Index Measured by Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) Staining After KLH Stimulation (Part A)(Days 0, 9, 16)
- Suppression (or Non-activation) of T Cell Stimulation Index Measured by CFSE Staining After KLH Stimulation (Part B)(Day 42)
- Other Mechanistic Assessments on Archived Serum Samples Like Anti-KLH Antibodies and Secreted Cytokines (Part B)(6 months)
- Compare the Level of KLH-specific Antibodies in the Serum (Samples From Various Time Points) Between Parts A and B(6 months)