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Responses to Immunization With Keyhole Limpet Hemocyanin Administered by Scarification and the Intradermal Route

This study has been completed.
Sponsor:
Collaborator:
Atopic Dermatitis and Vaccinia Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00614731
First received: February 11, 2008
Last updated: January 8, 2013
Last verified: January 2013
  Purpose

Atopic dermatitis (AD) is a skin disorder in which people often have swelling and skin infections. People with this disease cannot receive the smallpox vaccine because it could cause them to have a fatal reaction known as eczema vaccinatum (EV). Keyhole limpet hemocyanin (KLH) is a protein that can be used to deliver vaccines to the body. The purpose of this study is to determine a baseline immune reaction to KLH in people without AD. Once this has been established, other studies can be designed to determine whether KLH can be used to give vaccines to people with AD.


Condition Intervention Phase
Atopic Dermatitis
Biological: KLH carrier-protein
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Responses to Immunization With Keyhole Limpet Hemocyanin Administered by Scarification and the Intradermal Route

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Change in anti-KLH IgG antibody response to two vaccinations of KLH in nonatopic participants [ Time Frame: At baseline and Day 47 ] [ Designated as safety issue: No ]
  • Safety of administering KLH by scarification route as measured by proportion of subjects with any treatment-emergent abnormalities in vital signs (body temperature, heart rate, respirations, and blood pressure) and liver function [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in anti-KLH antibody responses in IgG subclasses 1 to 4, IgA, IgM, and IgE. [ Time Frame: At baseline and Day 47 ] [ Designated as safety issue: No ]
  • Incidence of all adverse events (AEs) [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Change in diameter of delayed type hypersensitivity (DTH) responses to KLH [ Time Frame: At Day 2 and 49 ] [ Designated as safety issue: No ]
  • Induction of a T cell response as measured by a change from negative (smaller than 5 mm) to positive (5 mm or larger) DTH reaction. [ Time Frame: At Days 2 and 49 ] [ Designated as safety issue: No ]
  • Presence or absence of antibody response as measured by whether or not there is a greater than 2 fold increase in antibody (IgG, IgA, IgM, IgE) titers to two administrations of KLH. [ Time Frame: At Days 0 and 47 ] [ Designated as safety issue: No ]
  • Changes pre- versus post-administration of KLH in quantitative levels of clinical labs (CBC, liver function [AST, ALT], renal function [creatinine, BUN]) [ Time Frame: At Days 0 and 47 ] [ Designated as safety issue: Yes ]
  • Changes pre- versus post-administration of KLH in quantitative levels of vital signs (body temperature, heart rate, respirations, blood pressure) [ Time Frame: At Days 0 and 47 ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: December 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ID immunizations (100 mcg)
Participants will receive a total of two 100 mcg intradermal (ID) KLH immunizations with 1 mg/ml KLH per immunization. Immunizations will be given 21 days apart at Visits 5 and 6.
Biological: KLH carrier-protein
KLH carrier-protein vaccination containing no other protein or antibodies
Other Names:
  • Immucothel
  • Vacmune
Experimental: Scarification by 3 jabs
Participants will receive two scarification immunizations by 3 jabs containing 20 mg/ml of KLH. The immunizations will occur 21 days apart at Visits 5 and 6.
Biological: KLH carrier-protein
KLH carrier-protein vaccination containing no other protein or antibodies
Other Names:
  • Immucothel
  • Vacmune
Experimental: ID immunizations (250 mcg)
Enrollment will begin after the safety data for Groups 1A and 2A have been reviewed. Participants in this group will receive two 250 mcg ID KLH vaccinations containing 10 mg/ml of KLH. Immunizations will occur 21 days apart at Visits 5 and 6.
Biological: KLH carrier-protein
KLH carrier-protein vaccination containing no other protein or antibodies
Other Names:
  • Immucothel
  • Vacmune
Experimental: Scarification by 15 jabs
Enrollment will begin after the safety data from groups 1A and 2A has been examined. Participants in this group will receive a total of two scarification immunizations by 5 needles used to administer 15 jabs, each containing, 20 mg/ml of KLH. Immunizations will occur 21 days apart at Visits 5 and 6.
Biological: KLH carrier-protein
KLH carrier-protein vaccination containing no other protein or antibodies
Other Names:
  • Immucothel
  • Vacmune

Detailed Description:

AD is characterized by skin inflammation and recurrent skin infections. In addition, people with AD may have a severe and sometimes fatal reaction to the smallpox vaccine called EV. KLH is a carrier protein that can be used to deliver antibodies to the body. However KLH itself, may cause an immune response. The purpose of this study is to determine the body's reaction to pure KLH in people without AD. This will be used to establish a baseline immune response and may be compared to the immune response in people with AD during future studies.

This study will last 8 weeks and will have 11 study visits. Participants in this study will be randomly assigned to 1 of 4 groups. All participants will receive their immunizations at Visits 5 and 6. Participants in Group 1A will receive 2 immunizations each with 100 mcg of KLH each. Participants in Group 2A will receive 2 immunizations through scarification (a shallow cut in the skin) with jabs, each containing 20 mg/mL of KLH. Adverse reactions will be monitored after each immunization. Once safety data from these 2 groups have been reviewed, the next 2 groups will be enrolled. Participants in Group 1B will receive 2 immunizations each with 250 mcg of KLH each. Participants in Group 2B will receive 2 immunizations through scarification with 15 jabs, each containing 20mg/mL of KLH. Other study visits will include allergy testing and blood and urine collection.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy and nonatopic as defined by the ADVN Standard Diagnostic Criteria
  • Willing to use appropriate forms of contraception

Exclusion Criteria:

  • Active bacterial, viral, or fungal infection within 30 days prior to study entry
  • Immunodeficiency
  • Received Use of systemic corticosteroids, antibiotics, antivirals, anti-inflammatory biologics (e.g., alefacept, etanercept), calcineurin inhibitors, oral immunosuppressive agents, anxiolytic agents, antidepressants, or cancer chemotherapy within 30 days prior to KLH administration
  • Use of topical corticosteroids, antibiotics, antivirals, immune enhancers, or calcineurin inhibitors within 7 days prior to study entry
  • Allergy to shellfish
  • Vaccination within 30 days prior to entering the study
  • Skin rash
  • Participation in a clinical trial within 4 weeks of study entry
  • Positive response to DTH test prior to administration of KLH
  • Previous exposure to KLH or products containing KLH
  • Allergic or hypersensitivity to KLH
  • Any condition that, in the opinion of the investigator, would interfere with the study
  • Pregnant or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00614731

Locations
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
Sponsors and Collaborators
Atopic Dermatitis and Vaccinia Network
Investigators
Principal Investigator: Henry Milgrom, M.D. National Jewish Health
Principal Investigator: Donald Y Leung, M.D., Ph.D. National Jewish Health
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00614731     History of Changes
Other Study ID Numbers: DAIT ADVN KLH 07, Contract No. HHSN266200400029C
Study First Received: February 11, 2008
Last Updated: January 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Keyhole Limpet Hemocyanin
KLH
atopic dermatitis
IgG antibodies
scarification

Additional relevant MeSH terms:
Dermatitis
Dermatitis, Atopic
Genetic Diseases, Inborn
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Skin Diseases
Skin Diseases, Eczematous
Skin Diseases, Genetic
Keyhole-limpet hemocyanin
Adjuvants, Immunologic
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014