Clinical trial NCT01489956: A Study to Determine the Immunogenicity and Oral Tolerance to Keyhole Limpet Hemocyanin (KLH)
Official title: Pilot Study to Determine the Immunogenicity of Immucothel® and Oral Tolerance Induction With Biosyn Native KLH in Healthy Subjects (ITN047AI)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Autoimmune Disorders
Keywords: Keyhole Limpet Hemocyanin (KLH)
Immucothel
Native KLH
Healthy volunteers
Oral tolerance
Immunogenicity
Autoimmune diseases
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2011-12-12
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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:

1. Ten evaluable (as defined by protocol) participants will be given Immucothel alone by injection on two occasions, If Immucothel alone creates an immune response in most of the participants then Part A will be completed.
2. If Immucothel alone does not create an immune response in most of the participants in Part A, then 10 new evaluable (as defined by protocol) participants will be asked to volunteer to test Immucothel in combination with the adjuvant Montanide (mineral oil). This will be given by injection on two occasions If there is an immune response in most of the participants to this combination of Immucothel and Montanide then Part A will be done.

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.

Eligibility criteria: Inclusion Criteria:

* Healthy
* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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)
timeFrame: Day 16
measure: 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)
timeFrame: Day 32
measure: T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A)
timeFrame: Day 9
measure: T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A)
timeFrame: Day 16
Secondary outcomes:
measure: Cytokine Secretion Profile of T Cells Stimulated by KLH (Part A)
timeFrame: Days 0, 9, 16
measure: T Cell Stimulation Index Measured by Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) Staining After KLH Stimulation (Part A)
timeFrame: Days 0, 9, 16
measure: Suppression (or Non-activation) of Cytokine Secretion Profile of T Cells Stimulated by KLH Following Oral Feeding (Part B)
timeFrame: Day 42
measure: Suppression (or Non-activation) of T Cell Stimulation Index Measured by CFSE Staining After KLH Stimulation (Part B)
timeFrame: Day 42
measure: Other Mechanistic Assessments on Archived Serum Samples Like Anti-KLH Antibodies and Secreted Cytokines (Part B)
timeFrame: 6 months
measure: Compare the Level of KLH-specific Antibodies in the Serum (Samples From Various Time Points) Between Parts A and B
timeFrame: 6 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Lloyd Mayer, MD
role: STUDY_CHAIR
References: