Trial Outcomes & Findings for A Study to Determine the Immunogenicity and Oral Tolerance to Keyhole Limpet Hemocyanin (KLH) (NCT NCT01489956)

Last Updated: 2016-04-12

Results Overview

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.

Recruitment status

TERMINATED

Study phase

EARLY_PHASE1

Target enrollment

19 participants

Primary outcome timeframe

Day 16

Results posted on

2016-04-12

Participant Flow

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

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	13	6
Overall Study COMPLETED	12	5
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Lost to Follow-up	1	0	0
Overall Study Withdrawal by Subject	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Immucothel Alone (Part A) n=13 Participants 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) n=6 Participants 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 n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	6 Participants n=7 Participants	19 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	6 participants n=7 Participants	19 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 16

Population: Intent-to-treat

Outcome measures

Outcome measures
Measure	Immucothel Alone (Part A) n=10 Participants 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.
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 participants	—	—

PRIMARY outcome

Timeframe: Day 32

Population: Intent-to-treat

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.

Outcome measures

Outcome measures
Measure	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) n=5 Participants 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.
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 participants

Adverse Events

Immucothel Alone (Part A)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Immucothel + Montanide (Part A)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Immucothel Alone or Immucothel + Montanide (Part B)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Immucothel Alone (Part A) n=13 participants at risk 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) n=6 participants at risk 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.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/13 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	16.7% 1/6 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Gastrointestinal disorders Nausea	0.00% 0/13 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	16.7% 1/6 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
General disorders Injection site reaction	0.00% 0/13 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	16.7% 1/6 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Infections and infestations Gingival infection	7.7% 1/13 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	0.00% 0/6 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Basophil count increased	0.00% 0/13 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	16.7% 1/6 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Basophil percentage increased	0.00% 0/13 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	16.7% 1/6 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Blood alkaline phosphatase increased	7.7% 1/13 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	0.00% 0/6 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Blood creatinine increased	7.7% 1/13 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	0.00% 0/6 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Eosinophil percentage increased	0.00% 0/13 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	16.7% 1/6 • Number of events 2 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Haematocrit decreased	7.7% 1/13 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	0.00% 0/6 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Haematocrit increased	0.00% 0/13 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	16.7% 1/6 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Haemoglobin decreased	15.4% 2/13 • Number of events 2 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	0.00% 0/6 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Haemoglobin increased	0.00% 0/13 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	33.3% 2/6 • Number of events 3 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Mean cell haemoglobin decreased	7.7% 1/13 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	0.00% 0/6 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations Red blood cell count decreased	7.7% 1/13 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	0.00% 0/6 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Investigations White blood cell count decreased	7.7% 1/13 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	33.3% 2/6 • Number of events 2 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Respiratory, thoracic and mediastinal disorders Cough	7.7% 1/13 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	0.00% 0/6 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.7% 1/13 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	0.00% 0/6 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects
Surgical and medical procedures Breast reconstruction	7.7% 1/13 • Number of events 1 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	— 0/0 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects	0.00% 0/6 • Enrollment through last study visit (up to 6 months after last immunization) Adverse events reported for all enrolled subjects