Trial Outcomes & Findings for A Post-Marketing Study of the Immunogenicity of Somatropin (Ribosomal Deoxyribo Nucleic Acid [rDNA] Origin) Injection (Nutropin AQ®) in Children With Growth Hormone Deficiency (NCT NCT02311894)

Results Overview

Participants who were tested positive to anti-GH antibody after initiation of study treatment.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

82 participants

Primary outcome timeframe

Baseline up to 1 year

Results posted on

2019-01-08

Participant Flow

Participant milestones

Participant milestones
Measure	Somatropin Children will receive daily subcutaneous (SC) injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.
Overall Study STARTED	82
Overall Study Modified ITT Population	81
Overall Study COMPLETED	78
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Somatropin Children will receive daily subcutaneous (SC) injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.
Overall Study Discontinued in error	1
Overall Study Lost to Follow-up	1
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

A Post-Marketing Study of the Immunogenicity of Somatropin (Ribosomal Deoxyribo Nucleic Acid [rDNA] Origin) Injection (Nutropin AQ®) in Children With Growth Hormone Deficiency

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Somatropin n=82 Participants Children will receive daily subcutaneous (SC) injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.
Age, Continuous	9.0 years STANDARD_DEVIATION 1.91 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	65 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	70 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	5 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=5 Participants
Race/Ethnicity, Customized Multiple	1 participants n=5 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants
Race/Ethnicity, Customized Unknown	3 participants n=5 Participants
Race/Ethnicity, Customized White	68 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 1 year

Population: All enrolled participants who received at least one dose of study drug and who had at least one post-baseline assessment

Participants who were tested positive to anti-GH antibody after initiation of study treatment.

Outcome measures

Outcome measures
Measure	Somatropin n=81 Participants Children will receive daily subcutaneous (SC) injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.
Percentage of Participants Who Develop Anti-GH Antibodies After Treatment With Nutropin AQ v1.1	3.7 percentage of participants Interval 0.77 to 10.44

SECONDARY outcome

Timeframe: Baseline up to 1 year

Population: All enrolled participants who received at least one dose of study drug and who had at least one post-baseline assessment

Growth attenuation is defined as initial growth response greater than pretreatment velocity followed by reduction in growth response to below the pretreatment velocity in the subsequent 6- to 12-month treatment period or reaching ≤ 2 cm per year.

Outcome measures

Outcome measures
Measure	Somatropin n=81 Participants Children will receive daily subcutaneous (SC) injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.
Percentage of Participants Who Exhibit Functional Growth Attenuation	2.6 percentage of participants Interval 0.31 to 8.96

SECONDARY outcome

Timeframe: Baseline up to 1 year

Population: Included only patients who had positive anti-GH antibody.

Among participants who developed positive anti-GH antibody post-baseline, participants who were tested positive to neutralizing anti-GH antibody during study participation.

Outcome measures

Outcome measures
Measure	Somatropin n=3 Participants Children will receive daily subcutaneous (SC) injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.
Percentage of Participants With Neutralizing Antibodies	0 percentage of participants

SECONDARY outcome

Timeframe: Months 6, 12

Population: All enrolled participants who received at least one dose of study drug and who had at least one post-baseline assessment

Annualized growth velocity is defined as (height - baseline height) / (date of height assessment - date of baseline)\*365.25. Results are presented according to anti-GH antibody status (positive included all participants that were anti-GH antibody positive at least once post-baseline visit and anti-GH antibody negative population included all participants that were anti-GH antibody negative at all post-baseline visits).

Outcome measures

Outcome measures
Measure	Somatropin n=81 Participants Children will receive daily subcutaneous (SC) injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.
Annualized Growth Velocity at Months 6 and 12 (Change From Baseline) 6 months (Anti-GH Antibody Positive)	5.3 cm/year Standard Deviation 2.89
Annualized Growth Velocity at Months 6 and 12 (Change From Baseline) 6 months (Anti-GH Antibody Negative)	5.5 cm/year Standard Deviation 2.64
Annualized Growth Velocity at Months 6 and 12 (Change From Baseline) 12 months (Anti-GH Antibody Positive)	5.2 cm/year Standard Deviation 3.61
Annualized Growth Velocity at Months 6 and 12 (Change From Baseline) 12 months (Anti-GH Antibody Negative)	4.9 cm/year Standard Deviation 2.40

SECONDARY outcome

Timeframe: Months 6, 12

Population: All enrolled participants who received at least one dose of study drug and who had at least one post-baseline assessment

Height Standard Deviation Score (SDS) allows for the comparison of a participants height to that of others in the same age group. Therefore, the average height for that age group will have the SDS of 0. In this study, the starting Height SDS score was ≤ -1.5 (≤ 5th percentile). Results are presented according to anti-GH antibody status (positive included all participants that were anti-GH antibody positive at least once post-baseline visit and anti-GH antibody negative population included all participants that were anti-GH antibody negative at all post-baseline visits.

Outcome measures

Outcome measures
Measure	Somatropin n=81 Participants Children will receive daily subcutaneous (SC) injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.
Height Standard Deviation Score (SDS) at Months 6 and 12 (Change From Baseline) 6 months (Anti-GH Antibody Positive)	0.3 SDS Standard Deviation 0.11
Height Standard Deviation Score (SDS) at Months 6 and 12 (Change From Baseline) 6 months (Anti-GH Antibody Negative)	0.4 SDS Standard Deviation 0.17
Height Standard Deviation Score (SDS) at Months 6 and 12 (Change From Baseline) 12 months (Anti-GH Antibody Positive)	0.8 SDS Standard Deviation 0.15
Height Standard Deviation Score (SDS) at Months 6 and 12 (Change From Baseline) 12 months (Anti-GH Antibody Negative)	0.7 SDS Standard Deviation 0.25

SECONDARY outcome

Timeframe: Baseline up to 1 year

Population: Include all participants who received at least one dose of study drug.

Among participants who received at least one dose of study drug, those who reported at least one adverse event during study participation.

Outcome measures

Outcome measures
Measure	Somatropin n=82 Participants Children will receive daily subcutaneous (SC) injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.
Percentage of Participants With Adverse Events	69.5 percentage of participants

Adverse Events

Somatropin

Serious events: 0 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Somatropin n=82 participants at risk Children will receive daily subcutaneous (SC) injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.
Gastrointestinal disorders Vomiting	14.6% 12/82 • Adverse events (AEs) were reported from Day 1 until 28 days after last dose of study medication for up to 12 months. The safety population included all participants who received at least 1 dose of the investigational product.
General disorders Injection site bruising	8.5% 7/82 • Adverse events (AEs) were reported from Day 1 until 28 days after last dose of study medication for up to 12 months. The safety population included all participants who received at least 1 dose of the investigational product.
General disorders Pyrexia	6.1% 5/82 • Adverse events (AEs) were reported from Day 1 until 28 days after last dose of study medication for up to 12 months. The safety population included all participants who received at least 1 dose of the investigational product.
Infections and infestations Upper respiratory tract infection	9.8% 8/82 • Adverse events (AEs) were reported from Day 1 until 28 days after last dose of study medication for up to 12 months. The safety population included all participants who received at least 1 dose of the investigational product.
Infections and infestations Pharyngitis streptococcal	7.3% 6/82 • Adverse events (AEs) were reported from Day 1 until 28 days after last dose of study medication for up to 12 months. The safety population included all participants who received at least 1 dose of the investigational product.
Infections and infestations Nasopharyngitis	6.1% 5/82 • Adverse events (AEs) were reported from Day 1 until 28 days after last dose of study medication for up to 12 months. The safety population included all participants who received at least 1 dose of the investigational product.
Nervous system disorders Headache	20.7% 17/82 • Adverse events (AEs) were reported from Day 1 until 28 days after last dose of study medication for up to 12 months. The safety population included all participants who received at least 1 dose of the investigational product.
Skin and subcutaneous tissue disorders Rash	7.3% 6/82 • Adverse events (AEs) were reported from Day 1 until 28 days after last dose of study medication for up to 12 months. The safety population included all participants who received at least 1 dose of the investigational product.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER