Trial Outcomes & Findings for Cockroach Immunotherapy in Children and Adolescents (NCT NCT03541187)

Last Updated: 2023-05-22

Results Overview

The study's primary endpoint is the mean TNSS change from baseline to 12 months, calculated as the difference between baseline and 12-month mean TNSS up to baseline responsive dose. TNSS (0-12) is the sum of three participant-assessed scores for rhinorrhea, congestion, itching, and staff-monitored sneezing, rated 0=None, 1=Mild, 2=Moderate, 3=Severe. Analysis uses ANCOVA modeling mean TNSS difference with factors for treatment arm, site, and baseline mean TNSS. Least square means (LSmeans), SEs, difference in LSmeans between treatment and placebo groups, 95% CI, and p-value are reported. A greater change in the LSmeans indicates a better outcome.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

82 participants

Primary outcome timeframe

After 12 months

Results posted on

2023-05-22

Participant Flow

Recruited 308 participants with the goal of enrolling 80 participants into this trial. Each participant received a 12 month treatment.

Participant milestones

Participant milestones
Measure	Cockroach SCIT Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. German cockroach allergenic extract: Active ingredient: a non-standardized allergen derived from the extraction and purification of proteins from German cockroach (Blattella germanica). Non-standardized glycerinated German cockroach allergenic extract is approved in the United States for diagnostic skin testing and immunotherapy by subcutaneous injection (U.S. License 467).	Placebo Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. Placebo for German cockroach allergenic extract: Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).
Overall Study STARTED	40	42
Overall Study COMPLETED	28	29
Overall Study NOT COMPLETED	12	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Cockroach SCIT Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. German cockroach allergenic extract: Active ingredient: a non-standardized allergen derived from the extraction and purification of proteins from German cockroach (Blattella germanica). Non-standardized glycerinated German cockroach allergenic extract is approved in the United States for diagnostic skin testing and immunotherapy by subcutaneous injection (U.S. License 467).	Placebo Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. Placebo for German cockroach allergenic extract: Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).
Overall Study Lost to Follow-up	2	6
Overall Study Pregnancy	0	1
Overall Study Withdrawal by Subject	6	2
Overall Study Moved out of town	1	0
Overall Study >2 bursts of systemic corticosteroids for asthma during treatment period (Starting Nov 2020)	1	2
Overall Study Did not meet randomization criteria	1	1
Overall Study Potential inability to tolerate maintenance dose	1	0
Overall Study Need for dose >500 mcg of fluticasone for 6 months	0	1

Baseline Characteristics

Count of participants with an annual household income that falls below $15,000 per year.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cockroach SCIT n=28 Participants Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. German cockroach allergenic extract: Active ingredient: a non-standardized allergen derived from the extraction and purification of proteins from German cockroach (Blattella germanica). Non-standardized glycerinated German cockroach allergenic extract is approved in the United States for diagnostic skin testing and immunotherapy by subcutaneous injection (U.S. License 467).	Placebo n=29 Participants Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. Placebo for German cockroach allergenic extract: Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).	Total n=57 Participants Total of all reporting groups
Age, Continuous	12.1 years STANDARD_DEVIATION 2.48 • n=28 Participants	12.2 years STANDARD_DEVIATION 2.49 • n=29 Participants	12.1 years STANDARD_DEVIATION 2.46 • n=57 Participants
Age, Customized Between 8 and 11 years	12 Participants n=28 Participants	11 Participants n=29 Participants	23 Participants n=57 Participants
Age, Customized ≥ 12 years	16 Participants n=28 Participants	18 Participants n=29 Participants	34 Participants n=57 Participants
Sex: Female, Male Female	12 Participants n=28 Participants	14 Participants n=29 Participants	26 Participants n=57 Participants
Sex: Female, Male Male	16 Participants n=28 Participants	15 Participants n=29 Participants	31 Participants n=57 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=28 Participants	1 Participants n=29 Participants	1 Participants n=57 Participants
Race (NIH/OMB) Asian	0 Participants n=28 Participants	0 Participants n=29 Participants	0 Participants n=57 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=28 Participants	0 Participants n=29 Participants	0 Participants n=57 Participants
Race (NIH/OMB) Black or African American	21 Participants n=28 Participants	16 Participants n=29 Participants	37 Participants n=57 Participants
Race (NIH/OMB) White	2 Participants n=28 Participants	5 Participants n=29 Participants	7 Participants n=57 Participants
Race (NIH/OMB) More than one race	3 Participants n=28 Participants	3 Participants n=29 Participants	6 Participants n=57 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=28 Participants	4 Participants n=29 Participants	6 Participants n=57 Participants
Region of Enrollment United States	28 participants n=28 Participants	29 participants n=29 Participants	57 participants n=57 Participants
Caretaker completed high school Yes	23 Participants n=28 Participants	23 Participants n=29 Participants	46 Participants n=57 Participants
Caretaker completed high school No	5 Participants n=28 Participants	6 Participants n=29 Participants	11 Participants n=57 Participants
Annual household income (<15k) Yes	12 Participants n=28 Participants • Count of participants with an annual household income that falls below $15,000 per year.	16 Participants n=29 Participants • Count of participants with an annual household income that falls below $15,000 per year.	28 Participants n=57 Participants • Count of participants with an annual household income that falls below $15,000 per year.
Annual household income (<15k) No	15 Participants n=28 Participants • Count of participants with an annual household income that falls below $15,000 per year.	13 Participants n=29 Participants • Count of participants with an annual household income that falls below $15,000 per year.	28 Participants n=57 Participants • Count of participants with an annual household income that falls below $15,000 per year.
Annual household income (<15k) Dont Know	1 Participants n=28 Participants • Count of participants with an annual household income that falls below $15,000 per year.	0 Participants n=29 Participants • Count of participants with an annual household income that falls below $15,000 per year.	1 Participants n=57 Participants • Count of participants with an annual household income that falls below $15,000 per year.
Cockroach-specific IgE at Baseline	7.9 kUA/L n=26 Participants • Insufficient blood volume led to missing data for 2 participants.	2.6 kUA/L n=29 Participants • Insufficient blood volume led to missing data for 2 participants.	4.6 kUA/L n=55 Participants • Insufficient blood volume led to missing data for 2 participants.
Cockroach-specific IgG4 at Baseline	35.0 ng/mL n=26 Participants • Insufficient blood volume led to missing data for 2 participants.	35.0 ng/mL n=29 Participants • Insufficient blood volume led to missing data for 2 participants.	35.0 ng/mL n=55 Participants • Insufficient blood volume led to missing data for 2 participants.
NAC responsive dose at baseline Reactive Dose 1 at NAC Baseline - 0 mcg/mL	0 Participants n=28 Participants	0 Participants n=29 Participants	0 Participants n=57 Participants
NAC responsive dose at baseline Reactive Dose 2 at NAC Baseline - 0.00492 mcg/mL	2 Participants n=28 Participants	2 Participants n=29 Participants	4 Participants n=57 Participants
NAC responsive dose at baseline Reactive Dose 3 at NAC Baseline - 0.0155 mcg/mL	3 Participants n=28 Participants	3 Participants n=29 Participants	6 Participants n=57 Participants
NAC responsive dose at baseline Reactive Dose 4 at NAC Baseline - 0.0490 mcg/mL	1 Participants n=28 Participants	1 Participants n=29 Participants	2 Participants n=57 Participants
NAC responsive dose at baseline Reactive Dose 5 at NAC Baseline - 0.155 mcg/mL	4 Participants n=28 Participants	2 Participants n=29 Participants	6 Participants n=57 Participants
NAC responsive dose at baseline Reactive Dose 6 at NAC Baseline - 0.489 mcg/mL	5 Participants n=28 Participants	6 Participants n=29 Participants	11 Participants n=57 Participants
NAC responsive dose at baseline Reactive Dose 7 at NAC Baseline - 1.54 mcg/mL	6 Participants n=28 Participants	3 Participants n=29 Participants	9 Participants n=57 Participants
NAC responsive dose at baseline Reactive Dose 8 at NAC Baseline - 4.88 mcg/mL	3 Participants n=28 Participants	9 Participants n=29 Participants	12 Participants n=57 Participants
NAC responsive dose at baseline Reactive Dose 9 at NAC Baseline - 15.4 mcg/mL	4 Participants n=28 Participants	3 Participants n=29 Participants	7 Participants n=57 Participants

PRIMARY outcome

Timeframe: After 12 months

Population: All participants who are randomized, received at least one dose of study treatment, and receive at least one dose during the 12-month NAC.

Outcome measures

Outcome measures
Measure	Cockroach SCIT n=28 Participants Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. German cockroach allergenic extract: Active ingredient: a non-standardized allergen derived from the extraction and purification of proteins from German cockroach (Blattella germanica). Non-standardized glycerinated German cockroach allergenic extract is approved in the United States for diagnostic skin testing and immunotherapy by subcutaneous injection (U.S. License 467).	Placebo n=29 Participants Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. Placebo for German cockroach allergenic extract: Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).
Change in Mean Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo	-1.02 score on a scale Standard Error 0.37	-0.79 score on a scale Standard Error 0.35

SECONDARY outcome

Timeframe: After 12 months

Population: All participants who sign consent and undergo study procedures at Screening.

Summary tables will present the total number of Immunotherapy related adverse event within the course of treatment.

Outcome measures

Outcome measures
Measure	Cockroach SCIT n=40 Participants Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. German cockroach allergenic extract: Active ingredient: a non-standardized allergen derived from the extraction and purification of proteins from German cockroach (Blattella germanica). Non-standardized glycerinated German cockroach allergenic extract is approved in the United States for diagnostic skin testing and immunotherapy by subcutaneous injection (U.S. License 467).	Placebo n=42 Participants Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. Placebo for German cockroach allergenic extract: Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).
Number of Immunotherapy Related Adverse Events and Number of Immunotherapy Related Serious Adverse Events in the Course of Treatment. Number of Immunotherapy Related Adverse Events	130 Adverse Events	36 Adverse Events
Number of Immunotherapy Related Adverse Events and Number of Immunotherapy Related Serious Adverse Events in the Course of Treatment. Number of Immunotherapy Related Serious Adverse Events	0 Adverse Events	0 Adverse Events

SECONDARY outcome

Timeframe: After 12 months

Population: All participants who are randomized, received at least one dose of study treatment, and receive at least one dose during the 12-month NAC.

The Total Nasal Symptom Score (TNSS) Area under the curve (AUC) will be calculated separately at baseline and 12 months for each subject using the trapezoidal rule and divided by their baseline reactive dose. TNSS (0-12) is the sum of three participant-assessed scores for rhinorrhea, congestion, itching, and staff-monitored sneezing, rated 0=None, 1=Mild, 2=Moderate, 3=Severe. Analysis uses ANCOVA modeling AUC TNSS with factors for treatment arm, site, and baseline TNSS AUC. Least square means (LSmeans), SEs, difference in LSmeans between treatment and placebo groups, 95% CI, and p-value are reported. A greater change in the LSmeans indicates a better outcome.

Outcome measures

Outcome measures
Measure	Cockroach SCIT n=28 Participants Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. German cockroach allergenic extract: Active ingredient: a non-standardized allergen derived from the extraction and purification of proteins from German cockroach (Blattella germanica). Non-standardized glycerinated German cockroach allergenic extract is approved in the United States for diagnostic skin testing and immunotherapy by subcutaneous injection (U.S. License 467).	Placebo n=29 Participants Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. Placebo for German cockroach allergenic extract: Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).
Change in Area Under the Curve (AUC) Total Nasal Symptom Score (TNSS) From Baseline to 12 Months Between Cockroach SCIT and Placebo	-0.65 score on a scale Standard Error 0.33	-0.48 score on a scale Standard Error 0.31

SECONDARY outcome

Timeframe: After 12 months

Population: All participants who are randomized, received at least one dose of study treatment, and receive at least one dose during the 12-month NAC.

The 12-month responsive dose is being calculated as the first dose that triggers a reaction of TNSS (Total Nasal Symptom Score) greater than or equal to 6 or a sneeze score of 3, whichever occurs first, in a sequence of up to 9 doses. To estimate the hazard ratio and 95% confidence interval, we are conducting an analysis using Cox regression with censoring, while controlling for the baseline responsive dose and site. Participants who do not experience a reaction before reaching the last dose will be considered right-censored.

Outcome measures

Outcome measures
Measure	Cockroach SCIT n=28 Participants Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. German cockroach allergenic extract: Active ingredient: a non-standardized allergen derived from the extraction and purification of proteins from German cockroach (Blattella germanica). Non-standardized glycerinated German cockroach allergenic extract is approved in the United States for diagnostic skin testing and immunotherapy by subcutaneous injection (U.S. License 467).	Placebo n=29 Participants Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. Placebo for German cockroach allergenic extract: Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).
Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo Reactive Dose 1 at 12 Months - 0 mcg/mL	2 Participants	0 Participants
Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo Reactive Dose 2 at 12 Months -0.00492 mcg/mL	1 Participants	0 Participants
Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo Reactive Dose 3 at 12 Months - 0.0155mcg/mL	1 Participants	3 Participants
Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo Reactive Dose 4 at 12 Months - 0.0490 mcg/mL	3 Participants	1 Participants
Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo Reactive Dose 5 at 12 Months - 0.155 mcg/mL	1 Participants	4 Participants
Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo Reactive Dose 6 at 12 Months - 0.489 mcg/mL	4 Participants	1 Participants
Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo Reactive Dose 7 at 12 Months - 1.54mcg/mL	1 Participants	7 Participants
Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo Reactive Dose 8 at 12 Months - 4.88 mcg/mL	1 Participants	3 Participants
Change in 12-month Responsive Dose Between Cockroach SCIT and Placebo Reactive Dose 9 at 12 Months - 15.4 mcg/mL	14 Participants	10 Participants

SECONDARY outcome

Timeframe: After 12 months

Population: All participants who are randomized, received at least one dose of study treatment, and receive at least one dose during the 12-month NAC.

The difference in log-transformed German Cockroach-specific IgE between baseline and 12 months is being modeled using ANCOVA with factors for treatment arm, site, and the respective log-transformed IgE baseline as covariates. For each treatment group, we present least square means (LSmeans) and their associated standard errors (SEs). We report the difference in LSmeans between the treatment and placebo groups, along with the associated 95% confidence interval (CI) and p-value.

Outcome measures

Outcome measures
Measure	Cockroach SCIT n=26 Participants Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. German cockroach allergenic extract: Active ingredient: a non-standardized allergen derived from the extraction and purification of proteins from German cockroach (Blattella germanica). Non-standardized glycerinated German cockroach allergenic extract is approved in the United States for diagnostic skin testing and immunotherapy by subcutaneous injection (U.S. License 467).	Placebo n=29 Participants Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. Placebo for German cockroach allergenic extract: Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).
Change in Log-transformed German Cockroach-specific IgE From Baseline to 12 Months Between Cockroach SCIT and Placebo	-0.56 Log(kuA/L) Standard Error 0.20	-0.53 Log(kuA/L) Standard Error 0.19

SECONDARY outcome

Timeframe: After 12 months

Population: All participants who are randomized, received at least one dose of study treatment, and receive at least one dose during the 12-month NAC.

The difference in log-transformed German Cockroach-specific IgG4 between baseline and 12 months is being modeled using ANCOVA with factors for treatment arm, site, and the respective log-transformed IgG4 baseline as covariates. For each treatment group, we present least square means (LSmeans) and their associated standard errors (SEs). We report the difference in LSmeans between the treatment and placebo groups, along with the associated 95% confidence interval (CI) and p-value.

Outcome measures

Outcome measures
Measure	Cockroach SCIT n=26 Participants Subcutaneous immunotherapy (SCIT): German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. German cockroach allergenic extract: Active ingredient: a non-standardized allergen derived from the extraction and purification of proteins from German cockroach (Blattella germanica). Non-standardized glycerinated German cockroach allergenic extract is approved in the United States for diagnostic skin testing and immunotherapy by subcutaneous injection (U.S. License 467).	Placebo n=29 Participants Subcutaneous immunotherapy (SCIT): Placebo for German cockroach allergenic extract. 40 participants 8 to 17 years of age will be randomized to this treatment arm. -In the first stage of dose escalation, up to 2 doses of the assigned SCIT treatment will be given weekly, separated by a minimum of 2 days. During the second phase of dose escalation, up to 1 dose of the assigned SCIT treatment will be given weekly, separated by a minimum of 5 days. After maintenance dose is achieved, participants will receive two additional maintenance level-doses spaced approximately 2 weeks apart, followed by maintenance injections every 4 weeks for the remainder of the treatment period. The treatment is for a period of 12 months. Placebo for German cockroach allergenic extract: Commercially- labeled licensed product, sterile diluent for allergenic extract (50% glycerinated), sodium bicarbonate (0.091%) sodium chloride (0.166%).
Change in Log-transformed German Cockroach-specific IgG4 From Baseline to 12 Months Between Cockroach SCIT and Placebo	-1.58 Log(ng/mL) Standard Error 0.22	-6.90 Log(ng/mL) Standard Error 0.21

OTHER_PRE_SPECIFIED outcome

Timeframe: Month 10, Month 12

The Composite Asthma Severity Index (CASI) is a comprehensive severity scale combining multiple facets of asthma severity: impairment, risk, and treatment. The CASI score ranges from 0 to 20 points, with higher scores indicating higher levels of severity, and includes 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations.