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: March 11, 2016
Last verified: March 2016
Results First Received: December 24, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Autoimmune Disorders
Interventions: Biological: Immucothel Alone (Part A)
Biological: Immucothel+Montanide (Part A)
Biological: Immucothel Alone or Immucothel+Montanide (Part B)

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
One site in the United States recruited 19 healthy adult male and female participants.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The accrual objective was 10 to 20 evaluable participants in Part A and 10 evaluable participants in Part B. The definition of an evaluable participant (measured/determined by lymphocyte proliferation assay) was provided in the protocol.

Reporting Groups
  Description
Immucothel Alone (Part A) Subjects received 100 µg Immucothel subcutaneously (SQ) on Day 0 and Day 9. If at least nine of the subjects demonstrated an immune response, Part A of the study would be complete.
Immucothel + Montanide (Part A) If an immune response was not observed in at least nine of the subjects 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. If at least nine of the subjects had an immune response after receiving Immucothel plus Montanide, Part A of the study would be completed.
Immucothel Alone or Immucothel + Montanide (Part B) Ten new, healthy participants ingested 50 mg of native keyhole limpet hemocyanin (KLH) orally. KLH, a protein extracted from a mollusk (a sea animal), was ingested 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.

Participant Flow:   Overall Study
    Immucothel Alone (Part A)     Immucothel + Montanide (Part A)     Immucothel Alone or Immucothel + Montanide (Part B)  
STARTED     13 [1]   0 [2]   6 [3]
COMPLETED     12     0     5  
NOT COMPLETED     1     0     1  
Lost to Follow-up                 1                 0                 0  
Withdrawal by Subject                 0                 0                 1  
[1] Ten of the 13 participants were considered evaluable.
[2] Nine of the 10 participants receiving Immucothel alone had a response, so Montanide was not used.
[3] These 6 subjects had Immucothel alone since Montanide was not needed for the 10 participants dosed.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled Sample

Reporting Groups
  Description
Immucothel Alone (Part A) Subjects received 100 µg Immucothel subcutaneously (SQ) on Day 0 and Day 9. If at least nine of the subjects demonstrated an immune response, Part A of the study would be complete.
Immucothel Alone or Immucothel + Montanide (Part B) Ten new, healthy participants ingested 50 mg of native keyhole limpet hemocyanin (KLH) orally. KLH, a protein extracted from a mollusk (a sea animal), was ingested 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.
Total Total of all reporting groups

Baseline Measures
    Immucothel Alone (Part A)     Immucothel Alone or Immucothel + Montanide (Part B)     Total  
Number of Participants  
[units: participants]
  13     6     19  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     13     6     19  
>=65 years     0     0     0  
Gender  
[units: participants]
     
Female     8     5     13  
Male     5     1     6  
Region of Enrollment  
[units: participants]
     
United States     13     6     19  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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)   [ Time Frame: Day 16 ]

2.  Primary:   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)   [ Time Frame: Day 32 ]

3.  Primary:   T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A)   [ Time Frame: Day 9 ]

4.  Primary:   T Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A)   [ Time Frame: Day 16 ]

5.  Secondary:   Cytokine Secretion Profile of T Cells Stimulated by KLH (Part A)   [ Time Frame: Days 0, 9, 16 ]

6.  Secondary:   T Cell Stimulation Index Measured by Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) Staining After KLH Stimulation (Part A)   [ Time Frame: Days 0, 9, 16 ]

7.  Secondary:   Suppression (or Non-activation) of Cytokine Secretion Profile of T Cells Stimulated by KLH Following Oral Feeding (Part B)   [ Time Frame: Day 42 ]

8.  Secondary:   Suppression (or Non-activation) of T Cell Stimulation Index Measured by CFSE Staining After KLH Stimulation (Part B)   [ Time Frame: Day 42 ]

9.  Secondary:   Other Mechanistic Assessments on Archived Serum Samples Like Anti-KLH Antibodies and Secreted Cytokines (Part B)   [ Time Frame: 6 months ]

10.  Secondary:   Compare the Level of KLH-specific Antibodies in the Serum (Samples From Various Time Points) Between Parts A and B   [ Time Frame: 6 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Director, Clinical Research Operations Program
Organization: DAIT/NIAID
phone: 301-594-7669
e-mail: DAITClinicalTrialsGov@niaid.nih.gov



Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01489956     History of Changes
Other Study ID Numbers: DAIT ITN047AI
Study First Received: December 1, 2011
Results First Received: December 24, 2015
Last Updated: March 11, 2016
Health Authority: United States: Food and Drug Administration
United States: Federal Government