Trial Outcomes & Findings for Biomarkers of Cockroach Sublingual Immunotherapy 2 (NCT NCT01380327)

Last Updated: 2014-06-11

Results Overview

Outcome is the ratio of geometric means for baseline versus post-baseline German cockroach-specific serum IgE. This result is an indicator of immune modulation over time, however its clinical significance is unclear.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

99 participants

Primary outcome timeframe

Baseline through 3 months of treatment

Results posted on

2014-06-11

Participant Flow

Five NIAID ICAC sites in the United States recruited the targeted number of study participants who fulfilled entry criteria between May 2011 and February 2012. Of the ninety-nine subjects enrolled in the study, eighty-nine achieved the milestone of randomization and are included in the Participant Flow: Overall Study Results Section.

Participant milestones

Participant milestones
Measure	Cockroach Sublingual Immunotherapy (SLIT) - High Dose Participants received twice-daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to seven escalating doses, or until the maximum study dose (840 microliters, 1:20 w/v) was achieved.	Cockroach Sublingual Immunotherapy (SLIT) - Low Dose Participants received daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to three escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.	Placebo Participants received daily (placebo-low dose) or twice-daily (placebo - high dose) doses of placebo placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The placebo was also administered during the preliminary dosing visits, up to three or seven escalating doses, or until the maximum study dose (420 or 840 microliters, 1:20 weight per volume \[w/v\]) was achieved.
Overall Study STARTED	30	31	28
Overall Study COMPLETED	27	28	21
Overall Study NOT COMPLETED	3	3	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Cockroach Sublingual Immunotherapy (SLIT) - High Dose Participants received twice-daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to seven escalating doses, or until the maximum study dose (840 microliters, 1:20 w/v) was achieved.	Cockroach Sublingual Immunotherapy (SLIT) - Low Dose Participants received daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to three escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.	Placebo Participants received daily (placebo-low dose) or twice-daily (placebo - high dose) doses of placebo placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The placebo was also administered during the preliminary dosing visits, up to three or seven escalating doses, or until the maximum study dose (420 or 840 microliters, 1:20 weight per volume \[w/v\]) was achieved.
Overall Study Lost to Follow-up	0	1	1
Overall Study Protocol Violation	3	2	3
Overall Study Withdrawal by Subject	0	0	1
Overall Study Housing situation precluded ability to k	0	0	1
Overall Study Questionable onset of epilepsy	0	0	1

Baseline Characteristics

Biomarkers of Cockroach Sublingual Immunotherapy 2

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cockroach Sublingual Immunotherapy (SLIT) - High Dose n=30 Participants Participants received twice-daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to seven escalating doses, or until the maximum study dose (840 microliters, 1:20 w/v) was achieved.	Cockroach Sublingual Immunotherapy (SLIT) - Low Dose n=31 Participants Participants received daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to three escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.	Placebo n=28 Participants Participants received daily (placebo-low dose) or twice-daily (placebo - high dose) doses of placebo placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The placebo was also administered during the preliminary dosing visits, up to three or seven escalating doses, or until the maximum study dose (420 or 840 microliters, 1:20 weight per volume \[w/v\]) was achieved.	Total n=89 Participants Total of all reporting groups
Age, Continuous	10.2 years STANDARD_DEVIATION 3.6 • n=99 Participants	11.0 years STANDARD_DEVIATION 3.3 • n=107 Participants	10.8 years STANDARD_DEVIATION 3.7 • n=206 Participants	10.7 years STANDARD_DEVIATION 3.5 • n=7 Participants
Sex: Female, Male Female	9 Participants n=99 Participants	9 Participants n=107 Participants	8 Participants n=206 Participants	26 Participants n=7 Participants
Sex: Female, Male Male	21 Participants n=99 Participants	22 Participants n=107 Participants	20 Participants n=206 Participants	63 Participants n=7 Participants
Region of Enrollment United States	30 participants n=99 Participants	31 participants n=107 Participants	28 participants n=206 Participants	89 participants n=7 Participants
German Cockroach-Specific Serum Immunoglobulin E (IgE) Levels	6.7 kU/L n=99 Participants	4.9 kU/L n=107 Participants	9.2 kU/L n=206 Participants	6.4 kU/L n=7 Participants
German Cockroach-Specific Serum Immunoglobulin G (IgG) Levels	4.1 mg/mL n=99 Participants	4.3 mg/mL n=107 Participants	5.1 mg/mL n=206 Participants	4.5 mg/mL n=7 Participants
German Cockroach-Specific Serum Immunoglobulin Subclass 4 (IgG4) Levels	0.1 mg/mL n=99 Participants	0.1 mg/mL n=107 Participants	0.5 mg/mL n=206 Participants	0.2 mg/mL n=7 Participants
German Cockroach-Specific IgE Fragment Antibody Binding (FAB) Activity	84.9 Percent antibody binding n=99 Participants	78.3 Percent antibody binding n=107 Participants	80.8 Percent antibody binding n=206 Participants	81.5 Percent antibody binding n=7 Participants
German Cockroach Prick Skin Test Wheal Size	5.0 mm n=99 Participants	5.0 mm n=107 Participants	5.8 mm n=206 Participants	5.3 mm n=7 Participants

PRIMARY outcome

Timeframe: Baseline through 3 months of treatment

Population: Intent-to-treat population with complete data.

Outcome measures

Outcome measures
Measure	Cockroach Sublingual Immunotherapy (SLIT) - High Dose n=30 Participants Participants received twice-daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to seven escalating doses, or until the maximum study dose (840 microliters, 1:20 w/v) was achieved.	Cockroach Sublingual Immunotherapy (SLIT) - Low Dose n=30 Participants Participants received daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to three escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.	Placebo n=28 Participants Participants received daily (placebo-low dose) or twice-daily (placebo - high dose) doses of placebo placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The placebo was also administered during the preliminary dosing visits, up to three or seven escalating doses, or until the maximum study dose (420 or 840 microliters, 1:20 weight per volume \[w/v\]) was achieved.
Change in German Cockroach-Specific Serum IgE Over Time	2.0 Ratio Interval 1.6 to 2.5	2.7 Ratio Interval 2.2 to 3.3	1.2 Ratio Interval 1.0 to 1.5

SECONDARY outcome

Timeframe: Baseline through 3 months of treatment

Population: Intent-to-treat population with complete data.

Outcome is the ratio of geometric means for baseline versus post-baseline German cockroach-specific serum immunoglobulin G (IgG). This result is an indicator of immune modulation over time, however its clinical significance is unclear.

Outcome measures

Outcome measures
Measure	Cockroach Sublingual Immunotherapy (SLIT) - High Dose n=30 Participants Participants received twice-daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to seven escalating doses, or until the maximum study dose (840 microliters, 1:20 w/v) was achieved.	Cockroach Sublingual Immunotherapy (SLIT) - Low Dose n=31 Participants Participants received daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to three escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.	Placebo n=28 Participants Participants received daily (placebo-low dose) or twice-daily (placebo - high dose) doses of placebo placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The placebo was also administered during the preliminary dosing visits, up to three or seven escalating doses, or until the maximum study dose (420 or 840 microliters, 1:20 weight per volume \[w/v\]) was achieved.
Change in German Cockroach-Specific Serum IgG Over Time	1.3 Ratio Interval 1.2 to 1.4	1.1 Ratio Interval 1.1 to 1.2	1.0 Ratio Interval 1.0 to 1.1

SECONDARY outcome

Timeframe: Baseline through 3 months of treatment

Population: Intent-to-treat population with complete data.

Outcome is the ratio of geometric means for baseline versus post-baseline German cockroach-specific serum immunoglobulin subclass 4 (IgG4). This result is an indicator of immune modulation over time, however its clinical significance is unclear.

Outcome measures

Outcome measures
Measure	Cockroach Sublingual Immunotherapy (SLIT) - High Dose n=29 Participants Participants received twice-daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to seven escalating doses, or until the maximum study dose (840 microliters, 1:20 w/v) was achieved.	Cockroach Sublingual Immunotherapy (SLIT) - Low Dose n=30 Participants Participants received daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to three escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.	Placebo n=27 Participants Participants received daily (placebo-low dose) or twice-daily (placebo - high dose) doses of placebo placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The placebo was also administered during the preliminary dosing visits, up to three or seven escalating doses, or until the maximum study dose (420 or 840 microliters, 1:20 weight per volume \[w/v\]) was achieved.
Change in German Cockroach-Specific Serum IgG4 Over Time	1.6 Ratio Interval 1.2 to 2.1	1.5 Ratio Interval 1.1 to 1.9	1.0 Ratio Interval 0.8 to 1.4

SECONDARY outcome

Timeframe: Baseline through 3 months of treatment

Population: Intent-to-treat population with complete data.

Outcome is change in mean IgE FAB activity level from baseline to post-baseline (status post 3 months of treatment). Serum from cockroach sublingual immunotherapy (SLIT)-treated participants were analyzed to determine if treatment inhibits in-vitro cockroach SLIT, using the per protocol allergenic extract doses. This result is an indicator of immune modulation over time, however its clinical significance is unclear.(Reference: Shamji MH et al. The IgE-facilitated allergen binding (FAB) assay: validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses. J Immunol Methods 2006;317(1-2): 71-9).

Outcome measures

Outcome measures
Measure	Cockroach Sublingual Immunotherapy (SLIT) - High Dose n=30 Participants Participants received twice-daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to seven escalating doses, or until the maximum study dose (840 microliters, 1:20 w/v) was achieved.	Cockroach Sublingual Immunotherapy (SLIT) - Low Dose n=28 Participants Participants received daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to three escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.	Placebo n=24 Participants Participants received daily (placebo-low dose) or twice-daily (placebo - high dose) doses of placebo placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The placebo was also administered during the preliminary dosing visits, up to three or seven escalating doses, or until the maximum study dose (420 or 840 microliters, 1:20 weight per volume \[w/v\]) was achieved.
Change in IgE Fragment Antibody Binding (FAB) Activity Over Time	-7.2 Percent antibody binding Interval -20.8 to 6.5	19.2 Percent antibody binding Interval 5.3 to 33.2	5.7 Percent antibody binding Interval -9.5 to 20.9

SECONDARY outcome

Timeframe: Participant enrollment to end of study (up to 3 months post-baseline)

Percent of participants who experienced at least one AE.

Outcome measures

Outcome measures
Measure	Cockroach Sublingual Immunotherapy (SLIT) - High Dose n=34 Participants Participants received twice-daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to seven escalating doses, or until the maximum study dose (840 microliters, 1:20 w/v) was achieved.	Cockroach Sublingual Immunotherapy (SLIT) - Low Dose n=33 Participants Participants received daily doses of glycerinated German cockroach (Blattella germanica) allergenic extract formulated in 50% glycerin at a concentration of 1:20 weight per volume \[w/v\] placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to three escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.	Placebo n=32 Participants Participants received daily (placebo-low dose) or twice-daily (placebo - high dose) doses of placebo placed under the tongue (sublingual route) to dissolve. The treatment course and study duration was 3 months. Note: The placebo was also administered during the preliminary dosing visits, up to three or seven escalating doses, or until the maximum study dose (420 or 840 microliters, 1:20 weight per volume \[w/v\]) was achieved.
Percent of Participants With the Occurrence of Adverse Events (AEs)	59 Percentage of population	76 Percentage of population	66 Percentage of population

Adverse Events

Cockroach Sublingual Immunotherapy (SLIT) - High Dose

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Cockroach Sublingual Immunotherapy (SLIT) - Low Dose

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cockroach Sublingual Immunotherapy (SLIT) - High Dose n=34 participants at risk Participants with German cockroach allergy and mild to moderate asthma, rhinitis, or both self-administered concentrated (1:20 weight per volume \[w/v\]) twice-daily doses of glycerinated German cockroach allergenic extract (50% glycerin) placed under the tongue (sublingually) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to seven escalating doses, or until the maximum study dose (840 microliters, 1:20 w/v) was achieved.	Cockroach Sublingual Immunotherapy (SLIT) - Low Dose n=33 participants at risk Participants with German cockroach allergy and mild to moderate asthma, rhinitis, or both self-administered concentrated (1:20 weight per volume \[w/v\]) daily doses of glycerinated German cockroach allergenic extract (50% glycerin) placed under the tongue (sublingually) to dissolve. The treatment course and study duration was 3 months. Note: The extract was also administered during the preliminary dosing visits, up to three escalating doses, or until the maximum study dose (420 microliters, 1:20 w/v) was achieved.	Placebo n=32 participants at risk Participants with German cockroach allergy and mild to moderate asthma, rhinitis, or both self-administered daily or twice-daily doses of placebo placed under the tongue (sublingually) to dissolve. The treatment course and study duration was 3 months. Note: The placebo was also administered during the preliminary dosing visits, up to three or seven escalating doses, or until the maximum study dose (420 or 840 microliters, 1:20 weight per volume \[w/v\]) was achieved.
Renal and urinary disorders Renal disorder	0.00% 0/34 • Participant enrollment to end of study (up to 3 months post-baseline) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/33 • Participant enrollment to end of study (up to 3 months post-baseline) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	3.1% 1/32 • Number of events 1 • Participant enrollment to end of study (up to 3 months post-baseline) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/34 • Participant enrollment to end of study (up to 3 months post-baseline) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/33 • Participant enrollment to end of study (up to 3 months post-baseline) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	3.1% 1/32 • Number of events 1 • Participant enrollment to end of study (up to 3 months post-baseline) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)

Other adverse events

Additional Information

Associate 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