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

NCT01489956 | Terminated Early Phase 1 Results DMC

• 1 other identifier: DAIT ITN047AI
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Autoimmune Disorders

Keywords

Keyhole Limpet Hemocyanin (KLH); Immucothel; Native KLH; Healthy volunteers; Oral tolerance; Immunogenicity; Autoimmune diseases

Outcome Measures

Primary Outcomes (4)

• 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)

  T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro keyhole limpet hemocyanin (KLH) stimulation of peripheral blood mononuclear cells (PBMC). An SI ≥3 on day 16 will indicate the presence of immune response. The SI is the ratio of 3H-thymidine incorporation by T cells in the presence of KLH stimulation to 3H-thymidine incorporation by T cells in the absence of stimulation. Higher values correspond with lower tolerance to KLH.

  Day 16

• 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)

  T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro keyhole limpet hemocyanin (KLH) stimulation of peripheral blood mononuclear cells (PBMC). An SI \<3 on Day 32 indicated tolerance to KLH. The SI is the ratio of 3H-thymidine incorporation by T cells in the presence of KLH stimulation to 3H-thymidine incorporation by T cells in the absence of stimulation. Higher values correspond with lower tolerance to KLH.

  Day 32

• T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A)

  No data available for analyses

  Day 9

• T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A)

  No data available for analyses.

  Day 16

Secondary Outcomes (6)

• Cytokine Secretion Profile of T Cells Stimulated by KLH (Part A)

  Days 0, 9, 16

• T Cell Stimulation Index Measured by Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) Staining After KLH Stimulation (Part A)

  Days 0, 9, 16

• Suppression (or Non-activation) of Cytokine Secretion Profile of T Cells Stimulated by KLH Following Oral Feeding (Part B)

  Day 42

• Suppression (or Non-activation) of T Cell Stimulation Index Measured by CFSE Staining After KLH Stimulation (Part B)

  Day 42

• Other Mechanistic Assessments on Archived Serum Samples Like Anti-KLH Antibodies and Secreted Cytokines (Part B)

  6 months

Study Arms (3)

Immucothel alone (Part A)

EXPERIMENTAL

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

Biological: Immucothel Alone (Part A)

Immucothel+Montanide (Part A)

EXPERIMENTAL

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.

Biological: Immucothel+Montanide (Part A)

Immucothel alone or Immucothel+Montanide (Part B)

EXPERIMENTAL

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.

Biological: Immucothel Alone or Immucothel+Montanide (Part B)

Interventions

Immucothel Alone (Part A) BIOLOGICAL

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

Also known as: keyhole limpet hemocyanin (KLH), Low Molecular Weight (LMW) KLH

Immucothel alone (Part A)

Immucothel+Montanide (Part A) BIOLOGICAL

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

Also known as: Immucothel® + Montanide ISA 51, LMW KLH +oil based adjuvant

Immucothel+Montanide (Part A)

Immucothel Alone or Immucothel+Montanide (Part B) BIOLOGICAL

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

Also known as: Immucothel® or Immucothel® + Montanide ISA 51, LMW KLH or LMW KLH +oil based adjuvant

Immucothel alone or Immucothel+Montanide (Part B)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator

Study Sites (1)

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Related Links

• National Institute of Allergy and Infectious DiseasesDivision of Allergy, Immunology, and Transplantation (DAIT)
• National Institute of Allergy and Infectious Diseases
• Immune Tolerance Network (ITN)

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

keyhole-limpet hemocyanin; montanide ISA 51

Condition Hierarchy (Ancestors)

Immune System Diseases

Limitations and Caveats

Data from 4 of the 5 evaluable subjects in Part B was negative for tolerance to KLH as defined by a stimulation index \<3 on day 42 after booster immunization. The study was terminated. Data were not collected and no analyses were performed.

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Lloyd Mayer, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2011
• First Posted: December 12, 2011
• Study Start: December 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: April 12, 2016
• Results First Posted: April 12, 2016

Record last verified: 2016-03

Locations

US (1)