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

NCT ID: NCT01489956

Last Updated: 2016-04-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2013-04-30

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.

Conditions

Autoimmune Disorders

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immucothel alone (Part A)

100 µg Immucothel subcutaneously (SQ) on Day 0 and Day 9.

Group Type: EXPERIMENTAL

Immucothel Alone (Part A)

Intervention Type: BIOLOGICAL

100 ug at day 0 (priming dose) and day 9(booster dose)

Immucothel+Montanide (Part A)

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.

Group Type: EXPERIMENTAL

Immucothel+Montanide (Part A)

Intervention Type: BIOLOGICAL

100 ug SQ Immucothel plus Montanide at day 0 (priming dose) and day 9 (booster dose)

Immucothel alone or Immucothel+Montanide (Part B)

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.

Group Type: EXPERIMENTAL

Immucothel Alone or Immucothel+Montanide (Part B)

Intervention Type: BIOLOGICAL

50 mg of native KLH on days 0-4 and 10-14 (total of 500 mg). Immunization on days 26 and 35.

Interventions

Immucothel Alone (Part A)

100 ug at day 0 (priming dose) and day 9(booster dose)

Intervention Type: BIOLOGICAL

Immucothel+Montanide (Part A)

100 ug SQ Immucothel plus Montanide at day 0 (priming dose) and day 9 (booster dose)

Intervention Type: BIOLOGICAL

Immucothel Alone or Immucothel+Montanide (Part B)

50 mg of native KLH on days 0-4 and 10-14 (total of 500 mg). Immunization on days 26 and 35.

Intervention Type: BIOLOGICAL

Other Intervention Names

keyhole limpet hemocyanin (KLH); Low Molecular Weight (LMW) KLH; Immucothel® + Montanide ISA 51; LMW KLH +oil based adjuvant; Immucothel® or Immucothel® + Montanide ISA 51; LMW KLH or LMW KLH +oil based adjuvant

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Immune Tolerance Network (ITN)

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lloyd Mayer, MD

Role: STUDY_CHAIR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai Medical Center

New York, New York, United States

Countries

United States

Related Links

http://www.niaid.nih.gov/about/organization/dait/pages/default.aspx

National Institute of Allergy and Infectious DiseasesDivision of Allergy, Immunology, and Transplantation (DAIT)

http://www.niaid.nih.gov/Pages/default.aspx

National Institute of Allergy and Infectious Diseases

http://www.immunetolerance.org/

Immune Tolerance Network (ITN)

Other Identifiers

DAIT ITN047AI

Identifier Type: -

Identifier Source: org_study_id