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TerminatedNCT01489956Updated Apr 12, 2016Results posted

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

An Early Phase 1 interventional study of Immucothel Alone (Part A) and Immucothel+Montanide (Part A) in Autoimmune Disorders, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Terminated at 1 site in United States. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-04-12.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Early Phase 1, Interventional, and Treatment

Why this study was terminated
Due to futility, identified after 5 subjects completed treatment in Part B
Phase
Early Phase 1
Study type
Interventional
Enrollment
19
Allocation
Non-randomized
Ages
18 Years to 50 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Autoimmune Disorders

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Keywords

  • Keyhole Limpet Hemocyanin (KLH)
  • Immucothel
  • Native KLH
  • Healthy volunteers
  • Oral tolerance
  • Immunogenicity
  • Autoimmune diseases
03

In context

Autoimmune Diseases

672 studies on the registry are indexed under Autoimmune Diseases; 272 are open to participants now.

This study's enrollment of 19 is below the median of 44 across 433 interventional studies indexed under Autoimmune Diseases.

Browse Autoimmune Diseases studies →

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,445 studies on the registry; 182 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 300 (75%) have results posted.

Browse National Institute of Allergy and Infectious Diseases (NIAID) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
19 participants (actual)

Study arms

  • Experimental
    Immucothel alone (Part A)

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

    Biological: Immucothel Alone (Part A)

  • Experimental
    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.

    Biological: Immucothel+Montanide (Part A)

  • Experimental
    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.

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

Interventions

  • BiologicalImmucothel Alone (Part A)

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

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

  • BiologicalImmucothel+Montanide (Part A)

    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

  • BiologicalImmucothel 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.

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

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Day 16

  2. 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.

    Time frame: Day 32

  3. 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

    Time frame: Day 9

  4. 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.

    Time frame: Day 16

Secondary outcomes

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

    No data available for analyses.

    Time frame: Days 0, 9, 16

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

    No data available for analyses.

    Time frame: Days 0, 9, 16

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

    No data available for analyses.

    Time frame: Day 42

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

    No data available for analyses.

    Time frame: Day 42

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

    No data available for analyses.

    Time frame: 6 months

  6. Compare the Level of KLH-specific Antibodies in the Serum (Samples From Various Time Points) Between Parts A and B

    No data available for analyses.

    Time frame: 6 months

07

Results

Posted Apr 12, 2016
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.

Participant flow

One site in the United States recruited 19 healthy adult male and female participants.

Participant flow — Overall Study
MilestoneImmucothel Alone (Part A)Immucothel + Montanide (Part A)Immucothel Alone or Immucothel + Montanide (Part B)
Started1306
Completed1205
Not completed101
Withdrew: Lost to follow-up100
Withdrew: Withdrawal by subject001

Outcome measures

PrimaryParticipants 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.

Time frame:
Day 16
Reported as:
Number · participants
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)
participantsImmucothel Alone (Part A)Immucothel + Montanide (Part A)Immucothel Alone or Immucothel + Montanide (Part B)
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)9——
PrimaryParticipants 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.

Time frame:
Day 32
Reported as:
Number · participants
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)
participantsImmucothel Alone (Part A)Immucothel + Montanide (Part A)Immucothel Alone or Immucothel + Montanide (Part B)
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)——1
PrimaryT Cell Stimulation Index (SI) as Measured by 3H-thymidine Incorporation After in Vitro KLH Stimulation of PBMC (Part A)

No data available for analyses

Time frame:
Day 9

No measurements were reported for this outcome.

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

No data available for analyses.

Time frame:
Day 16

No measurements were reported for this outcome.

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

No data available for analyses.

Time frame:
Days 0, 9, 16

No measurements were reported for this outcome.

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

No data available for analyses.

Time frame:
Days 0, 9, 16

No measurements were reported for this outcome.

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

No data available for analyses.

Time frame:
Day 42

No measurements were reported for this outcome.

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

No data available for analyses.

Time frame:
Day 42

No measurements were reported for this outcome.

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

No data available for analyses.

Time frame:
6 months

No measurements were reported for this outcome.

SecondaryCompare the Level of KLH-specific Antibodies in the Serum (Samples From Various Time Points) Between Parts A and B

No data available for analyses.

Time frame:
6 months

No measurements were reported for this outcome.

Adverse events

Collected over Enrollment through last study visit (up to 6 months after last immunization). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Immucothel Alone (Part A)—0/13 (0%)4/13 (30.8%)
Immucothel + Montanide (Part A)———
Immucothel Alone or Immucothel + Montanide (Part B)—0/6 (0%)4/6 (66.7%)
Most frequent other events
Showing 10 of 19
Most frequent other events
EventImmucothel Alone (Part A)Immucothel + Montanide (Part A)Immucothel Alone or Immucothel + Montanide (Part B)
Haemoglobin increasedInvestigations0/13—2/6
White blood cell count decreasedInvestigations1/13—2/6
Haemorrhoidal haemorrhageGastrointestinal disorders0/13—1/6
NauseaGastrointestinal disorders0/13—1/6
Injection site reactionGeneral disorders0/13—1/6
Basophil count increasedInvestigations0/13—1/6
Basophil percentage increasedInvestigations0/13—1/6
Eosinophil percentage increasedInvestigations0/13—1/6
Haematocrit increasedInvestigations0/13—1/6
Haemoglobin decreasedInvestigations2/13—0/6

Baseline characteristics

Enrolled Sample

Age, Categorical
Age, Categorical(Participants)Immucothel Alone (Part A)Immucothel Alone or Immucothel + Montanide (Part B)Total
<=18 years000
Between 18 and 65 years13619
>=65 years000
Sex: Female, Male
Sex: Female, Male(Participants)Immucothel Alone (Part A)Immucothel Alone or Immucothel + Montanide (Part B)Total
Female8513
Male516
Region of Enrollment
Region of Enrollment(participants)Immucothel Alone (Part A)Immucothel Alone or Immucothel + Montanide (Part B)Total
United States13619
08

Study locations

1 site
  • Mount Sinai Medical Center
    New York, New York 10029, United States
09

References and documents

10

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Dec 2011, a primary completion of Apr 2013 and a completion of Apr 2013. It does not say whether these dates are actual or estimated.

Results were first posted in Apr 2016, 3 years after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 1, 2011
First posted
Dec 12, 2011
Start
Dec 2011
Primary completionActual
Apr 2013
CompletionActual
Apr 2013
Results first posted
Apr 12, 2016
Last update
Apr 12, 2016
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 12, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01489956
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN)
Responsible party
Sponsor
First posted
Dec 12, 2011
Start date
Dec 2011
Primary completion
Apr 2013
Completion
Apr 2013
Results posted
Apr 12, 2016
Last update
Apr 12, 2016

Study contacts

Lloyd Mayer, MD
study chair · Icahn School of Medicine at Mount Sinai

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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