Growth Hormone Deficiency
Conditions
Brief summary
This is a Phase IV, multicenter, open-label, single-arm study of somatropin (rDNA origin) (Nutropin AQ v1.1) in pre-pubertal children with growth hormone deficiency (GHD) naïve to prior recombinant human growth hormone (rhGH) treatment. The study is designed to characterize the immunogenicity profile of somatropin (rDNA origin) injection when administered daily subcutaneously for 12 months. The clinical impact of immunogenicity will also be assessed.
Interventions
DRUGSomatropin
Somatropin will be administered as SC injections at a dose of up to 0.043 mg/kg/day. The dose may be adjusted for a change in body weight of at least (plus \[+\]/minus \[-\]) 2 kilograms (kg) from baseline at the Month 6 study visit or for a change in insulin-growth factor-1 (IGF-1), as per investigator assessment.
Sponsors
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
* Bone age less than equal to (\</=) 9 years (females) or \</= 11 years (males) as determined by X-ray of the left hand and wrist using Greulich and Pyle method and obtained within the 12 months prior to enrollment * Prepubertal (Tanner I) males and females by physical examination * Diagnosis of GHD (stimulated GH less than \[\<\] 10 nanograms per milliliter \[ng/mL\]) by two standard pharmacologic tests obtained up to 12 months prior to informed consent/assent * Normal thyroid function test within the 12 months prior to informed consent/assent * Normal complete blood counts within 12 months prior to informed consent/assent * Documentation of prior height and weight measurements, with height standard deviation score (SDS) \</= 5th percentile for idiopathic isolated GHD participants
Exclusion criteria
* Any previous rhGH treatment * Short stature etiologies other than GHD * Acute critical illness or uncontrolled chronic illness, which in the opinion of the investigator and medical monitor, would interfere with participation in this study, interpretation of the data, or pose a risk to participant safety * Chronic illnesses such as inflammatory bowel disease, celiac disease, heart disease, and diabetes * Bone diseases such as achondroplasia or hypochondroplasia, intracranial tumor, irradiation, and traumatic brain injury * Participants receiving oral or inhaled chronic corticosteroid therapy (greater than \[\>\] 3 months) for other medical conditions other than central adrenal insufficiency * Participants who require higher (2 times or greater than maintenance) doses of corticosteroids for more than 5 days in the 6 months prior to enrollment in the study * Participants with active malignancy or any other condition that the investigator believes would pose a significant hazard to the participant if rhGH were initiated * Females with Turner syndrome regardless of their GH status * Prader-Willi syndrome regardless of GH status * Born small for gestational age regardless of GH status * Presence of scoliosis requiring monitoring * Previous participation in another clinical trial or investigation of GH, treatment for growth failure, or treatment with a biologic agent * Participants with closed epiphyses * Participants with a known hypersensitivity to somatropin, excipients, or diluent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Develop Anti-GH Antibodies After Treatment With Nutropin AQ v1.1 | Baseline up to 1 year | Participants who were tested positive to anti-GH antibody after initiation of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Exhibit Functional Growth Attenuation | Baseline up to 1 year | 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. |
| Percentage of Participants With Neutralizing Antibodies | Baseline up to 1 year | Among participants who developed positive anti-GH antibody post-baseline, participants who were tested positive to neutralizing anti-GH antibody during study participation. |
| Annualized Growth Velocity at Months 6 and 12 (Change From Baseline) | Months 6, 12 | 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). |
| Height Standard Deviation Score (SDS) at Months 6 and 12 (Change From Baseline) | Months 6, 12 | 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. |
| Percentage of Participants With Adverse Events | Baseline up to 1 year | Among participants who received at least one dose of study drug, those who reported at least one adverse event during study participation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 82 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Discontinued in error | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Somatropin |
|---|---|
| Age, Continuous | 9.0 years STANDARD_DEVIATION 1.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized Asian | 5 participants |
| Race/Ethnicity, Customized Black or African American | 2 participants |
| Race/Ethnicity, Customized Multiple | 1 participants |
| Race/Ethnicity, Customized Other | 3 participants |
| Race/Ethnicity, Customized Unknown | 3 participants |
| Race/Ethnicity, Customized White | 68 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 82 |
| other Total, other adverse events | 40 / 82 |
| serious Total, serious adverse events | 0 / 82 |
Outcome results
Primary
Percentage of Participants Who Develop Anti-GH Antibodies After Treatment With Nutropin AQ v1.1
Participants who were tested positive to anti-GH antibody after initiation of study treatment.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin | Percentage of Participants Who Develop Anti-GH Antibodies After Treatment With Nutropin AQ v1.1 | 3.7 percentage of participants |
Secondary
Annualized Growth Velocity at Months 6 and 12 (Change From Baseline)
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).
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin | 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 |
| Somatropin | 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 |
| Somatropin | 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 |
| Somatropin | Annualized Growth Velocity at Months 6 and 12 (Change From Baseline) | 12 months (Anti-GH Antibody Negative) | 4.9 cm/year | Standard Deviation 2.4 |
Secondary
Height Standard Deviation Score (SDS) at Months 6 and 12 (Change From Baseline)
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin | 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 |
| Somatropin | 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 |
| Somatropin | 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 |
| Somatropin | 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
Percentage of Participants Who Exhibit Functional Growth Attenuation
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.
Time frame: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin | Percentage of Participants Who Exhibit Functional Growth Attenuation | 2.6 percentage of participants |
Secondary
Percentage of Participants With Adverse Events
Among participants who received at least one dose of study drug, those who reported at least one adverse event during study participation.
Time frame: Baseline up to 1 year
Population: Include all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin | Percentage of Participants With Adverse Events | 69.5 percentage of participants |
Secondary
Percentage of Participants With Neutralizing Antibodies
Among participants who developed positive anti-GH antibody post-baseline, participants who were tested positive to neutralizing anti-GH antibody during study participation.
Time frame: Baseline up to 1 year
Population: Included only patients who had positive anti-GH antibody.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin | Percentage of Participants With Neutralizing Antibodies | 0 percentage of participants |