A Study to Determine the Immunogenicity and Oral Tolerance to Keyhole Limpet Hemocyanin (KLH)

Autoimmune Disorders Clinical Trial

Official title:

Pilot Study to Determine the Immunogenicity of Immucothel and Oral Tolerance Induction With Biosyn Native KLH in Healthy Subjects (ITN047AI)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01489956
• Other study ID #: DAIT ITN047AI
• Status: Terminated
• Phase: Phase 0
• First received: December 1, 2011
• Last updated: December 20, 2013
• Start date: December 2011
• Est. completion date: April 2013

Study information

• Verified date: December 2013
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autoimmune Diseases
• Autoimmune Disorders

Intervention

Biological:
• Subcutaneous Immucothel
100 ug at day 0 (priming dose) and day 9(booster dose)
• Subcutaneous Immucothel plus Montanide
100 ug SQ Immunoclthel plus Montanide at day 0 (priming dose) and day 9 (booster dose)
• Oral KLH followed by immunization
50 mg of native KLH on days 0-4 and 10-14 (total of 500 mg). Immunization on days 26 and 35.

Locations

Country	Name	City	State
United States	Mount Sinai Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Immune Tolerance Network (ITN)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part A)	An SI>=3 after the booster immunization, day 16, will indicate the presence of immune response	Day 0	No
Primary	T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part B)	An SI <3 after the booster immunization will indicated tolerance.	Day 42	No
Primary	T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part A)		Day 9	No
Primary	T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part A)		Day 16	No
Secondary	Cytokine secretion profile of T cells stimulated by KLH (Part A)		Days 0, 9, 16	No
Secondary	T cell stimulation index measured by carboxyfluorescein diacetate succinimidyl ester (CFSE) staining after KLH stimulation. (Part A)		Days 0, 9, 16	No
Secondary	Suppression (or non-activation) of cytokine secretion profile of T cells stimulated by KLH following oral feeding.(Part B)		Day 42	No
Secondary	Suppression (or non-activation) of T cell stimulation index measured by CFSE staining after KLH stimulation.(Part B)		Day 42	No
Secondary	Other mechanistic assessments on archived serum samples like anti-KLH antibodies and secreted cytokines.(Part B)		6 months	No
Secondary	Compare the level of KLH-specific antibodies in the serum (samples from various time points) between Parts A and B.		6 months	No

External Links

•   Immune Tolerance Network (ITN)
•   National Institute of Allergy and Infectious Diseases