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

This study has been terminated.
(Due to futility, identified after 5 subjects completed treatment in Part B)
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01489956
First received: December 1, 2011
Last updated: December 20, 2013
Last verified: December 2013

December 1, 2011
December 20, 2013
December 2011
April 2013   (final data collection date for primary outcome measure)
  • T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part A) [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
    An SI>=3 after the booster immunization, day 16, will indicate the presence of immune response
  • T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part B) [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    An SI <3 after the booster immunization will indicated tolerance.
  • T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part A) [ Time Frame: Day 9 ] [ Designated as safety issue: No ]
  • T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part A) [ Time Frame: Day 16 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01489956 on ClinicalTrials.gov Archive Site
  • Cytokine secretion profile of T cells stimulated by KLH (Part A) [ Time Frame: Days 0, 9, 16 ] [ Designated as safety issue: No ]
  • T cell stimulation index measured by carboxyfluorescein diacetate succinimidyl ester (CFSE) staining after KLH stimulation. (Part A) [ Time Frame: Days 0, 9, 16 ] [ Designated as safety issue: No ]
  • Suppression (or non-activation) of cytokine secretion profile of T cells stimulated by KLH following oral feeding.(Part B) [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
  • Suppression (or non-activation) of T cell stimulation index measured by CFSE staining after KLH stimulation.(Part B) [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
  • Other mechanistic assessments on archived serum samples like anti-KLH antibodies and secreted cytokines.(Part B) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Compare the level of KLH-specific antibodies in the serum (samples from various time points) between Parts A and B. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Study to Determine the Immunogenicity and Oral Tolerance to Keyhole Limpet Hemocyanin (KLH)
Pilot Study to Determine the Immunogenicity of Immucothel and Oral Tolerance Induction With Biosyn Native KLH in Healthy Subjects (ITN047AI)

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:

  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.

Interventional
Phase 0
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Autoimmune Disorders
  • Biological: Subcutaneous Immucothel
    100 ug at day 0 (priming dose) and day 9(booster dose)
  • Biological: Subcutaneous Immucothel plus Montanide
    100 ug SQ Immunoclthel plus Montanide at day 0 (priming dose) and day 9 (booster dose)
  • Biological: 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.
  • Experimental: SQ Immucothel alone (Part A)
    Intervention: Biological: Subcutaneous Immucothel
  • Experimental: SQ Immucothel + Montanide (Part A)
    Intervention: Biological: Subcutaneous Immucothel plus Montanide
  • Experimental: Either Immucothel alone or Immucothel with Montanide. (Part B)
    Dependent on the results for Part A
    Intervention: Biological: Oral KLH followed by immunization
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
19
April 2013
April 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 50 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01489956
DAIT ITN047AI
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (ITN)
Study Chair: Lloyd Mayer, MD Mount Sinai School of Medicine
National Institute of Allergy and Infectious Diseases (NIAID)
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP