Growth Hormone Deficiency (GHD)
Conditions
Keywords
Adult Growth Hormone Deficiency (AGHD), immunogenicity, growth hormone, antibodies, GH biomarkers, IGF-I
Brief summary
To assess the immunogenicity of Saizen® solution for injection in adult subjects with documented Growth Hormone Deficiency (GHD).
Interventions
DRUGSaizen®
Single dose of Saizen® (recombinant human growth hormone, r-hGH) solution for injection will be administered subcutaneously for 26 weeks. Dosage regimen will be in accordance with marketed formulation of Saizen® (freeze-dried formulation), based on locally approved product labeling.
Sponsors
EMD Serono
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Adult male and female subjects, 18-60 years of age, inclusive, at the time the informed consent is signed * Subjects who have confirmed adult GHD * Subjects who are growth hormone (GH) treatment-naive or had received Saizen® (freeze-dried formulation) for pediatric GHD (PGHD), or are currently receiving Saizen® freeze-dried formulation for adult GHD (AGHD) * Subjects who have binding antibody-negative (BAbs-) at screening * Subjects who have no evidence of concomitant disease, intercurrent illness, or resultant therapy that would interfere with subject compliance, the evaluation of study results, or compromise the safety of the subject * Female subjects of childbearing potential who have a negative serum pregnancy test at the screening visit (and at each scheduled visit during the study) * Subjects who are willing to comply with the procedures of the study * Subjects who are willing to sign an Independent Ethics Committee/Institutional Review Board approved informed consent form * Other protocol-defined inclusion criteria may apply
Exclusion criteria
* Subjects who are currently receiving or have previously received treatment for adult GHD or any other indication, including PGHD, with a commercial GH product other than Saizen® freeze-dried formulation * Subjects who had a chronic underlying disease within 6 months prior to screening or concomitant medication(s) that in the opinion of the investigator would exclude the subject from the trial * Subjects who have significant renal impairment * Subjects who have diabetes mellitus * Subjects who are immunosuppressed * Subjects who have a current malignancy or a history of any malignancy (excluding fully-treated basal cell carcinoma) * Subjects who have participated in another study and received an investigational drug within 30 days prior to screening visit * Subjects who have clinically significant abnormal laboratory value(s) * Subjects who have known hypersensitivity or allergy to exogenous human GH or any of the excipients or phenol, the bacteriostatic agent in the Saizen® solution for injection * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Developed Positive Binding Antibodies (BAbs+) to Saizen® | Baseline up to Week 26 | Binding antibodies (BAbs) are all antibodies which are capable of binding to the investigational drug molecule (Saizen®), irrespective of their binding site. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Developed Positive Neutralizing Antibodies (NAbs+) to Saizen® | Baseline up to Week 26 | Neutralizing antibodies (NAbs) are defined as a subgroup of BAbs which bind to the active sites of the investigational drug molecule (Saizen®) and therefore neutralize its potency. |
| Insulin-like Growth Factor-I (IGF-1) Levels | Baseline, Week 2, Week 4, Week 8, Week 13, Week 18, Week 26 | — |
| Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Baseline, Week 2, Week 4, Week 8, Week 13, Week 18, Week 26 | Insulin-like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) was provided by the central laboratory; its calculation is based on the actual value of IGF-1 minus mean reference value of IGF-1 divided by reference standard deviation of IGF-1. |
| Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Baseline, Week 2, Week 4, Week 8, Week 13, Week 18, Week 26 | — |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Day 1 up to 28 days after last dose of study treatment | Adverse events (AEs): Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications. TEAEs: AEs occurring after the first administration of Saizen® solution for injection (on Day 1) up to the scheduled routine post treatment follow-up visit (4 weeks \[28 days\] after the final administration of Saizen® solution for injection). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Saizen® Single dose of Saizen® (recombinant human growth hormone, r-hGH) solution for injection will be administered subcutaneously for 26 weeks. Dosage regimen will be in accordance with marketed formulation of Saizen® (freeze-dried formulation), based on locally approved product labeling. | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Early termination of the trial | 36 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Saizen® |
|---|---|
| Age Continuous | 44.7 years STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 59 |
| serious Total, serious adverse events | 3 / 59 |
Outcome results
Primary
Number of Participants Who Developed Positive Binding Antibodies (BAbs+) to Saizen®
Binding antibodies (BAbs) are all antibodies which are capable of binding to the investigational drug molecule (Saizen®), irrespective of their binding site.
Time frame: Baseline up to Week 26
Population: Modified Intent-to-Treat (MITT) population consisted of all the participants who received at least 1 dose of study medication and had at least one post-baseline BAbs assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saizen® | Number of Participants Who Developed Positive Binding Antibodies (BAbs+) to Saizen® | 1 participants |
Secondary
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Time frame: Baseline, Week 2, Week 4, Week 8, Week 13, Week 18, Week 26
Population: Safety population consisted of all the participants who received at least 1 dose of study medication and had at least one post-baseline safety assessment. Here n signifies number of participants analyzed at that particular time point for each arm group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saizen® | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 2 (n = 49, 8) | 137.408 nmol/L | Standard Deviation 35.088 |
| Saizen® | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 13 (n = 47, 8) | 149.404 nmol/L | Standard Deviation 28.272 |
| Saizen® | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Baseline (n = 51, 8) | 124.941 nmol/L | Standard Deviation 31.899 |
| Saizen® | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 18 (n = 32, 4) | 148.813 nmol/L | Standard Deviation 39.754 |
| Saizen® | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 4 (n = 49, 8) | 144.592 nmol/L | Standard Deviation 32.632 |
| Saizen® | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 26 (n = 49, 8) | 152.429 nmol/L | Standard Deviation 35.649 |
| Saizen® | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 8 (n = 50, 8) | 147.460 nmol/L | Standard Deviation 36.381 |
| GH Treatment-Experienced | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 26 (n = 49, 8) | 147.500 nmol/L | Standard Deviation 30.402 |
| GH Treatment-Experienced | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 8 (n = 50, 8) | 156.625 nmol/L | Standard Deviation 36.19 |
| GH Treatment-Experienced | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Baseline (n = 51, 8) | 133.375 nmol/L | Standard Deviation 36.024 |
| GH Treatment-Experienced | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 2 (n = 49, 8) | 162.125 nmol/L | Standard Deviation 35.203 |
| GH Treatment-Experienced | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 4 (n = 49, 8) | 147.750 nmol/L | Standard Deviation 26.451 |
| GH Treatment-Experienced | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 13 (n = 47, 8) | 151.875 nmol/L | Standard Deviation 35.679 |
| GH Treatment-Experienced | Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels | Week 18 (n = 32, 4) | 155.500 nmol/L | Standard Deviation 36.235 |
Secondary
Insulin-like Growth Factor-I (IGF-1) Levels
Time frame: Baseline, Week 2, Week 4, Week 8, Week 13, Week 18, Week 26
Population: Safety population consisted of all the participants who received at least 1 dose of study medication and had at least one post-baseline safety assessment. 'N' (number of participants analyzed) = participants who were evaluated for this measure and n= participants who were analyzed at that particular time point for each arm group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saizen® | Insulin-like Growth Factor-I (IGF-1) Levels | Week 4 (n = 49, 8) | 19.914 nanomole per liter (nmol/L) | Standard Deviation 11.532 |
| Saizen® | Insulin-like Growth Factor-I (IGF-1) Levels | Week 13 (n = 46, 8) | 23.415 nanomole per liter (nmol/L) | Standard Deviation 8.02 |
| Saizen® | Insulin-like Growth Factor-I (IGF-1) Levels | Week 2 (n = 47, 8) | 18.923 nanomole per liter (nmol/L) | Standard Deviation 10.394 |
| Saizen® | Insulin-like Growth Factor-I (IGF-1) Levels | Week 18 (n = 31, 4) | 24.948 nanomole per liter (nmol/L) | Standard Deviation 9.3 |
| Saizen® | Insulin-like Growth Factor-I (IGF-1) Levels | Week 8 (n = 49, 8) | 21.155 nanomole per liter (nmol/L) | Standard Deviation 10.52 |
| Saizen® | Insulin-like Growth Factor-I (IGF-1) Levels | Week 26 (n = 48, 8) | 24.117 nanomole per liter (nmol/L) | Standard Deviation 11.085 |
| Saizen® | Insulin-like Growth Factor-I (IGF-1) Levels | Baseline (n = 49, 8) | 11.492 nanomole per liter (nmol/L) | Standard Deviation 6.694 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I (IGF-1) Levels | Week 26 (n = 48, 8) | 27.438 nanomole per liter (nmol/L) | Standard Deviation 12.402 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I (IGF-1) Levels | Baseline (n = 49, 8) | 20.225 nanomole per liter (nmol/L) | Standard Deviation 10.194 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I (IGF-1) Levels | Week 2 (n = 47, 8) | 28.663 nanomole per liter (nmol/L) | Standard Deviation 9.001 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I (IGF-1) Levels | Week 4 (n = 49, 8) | 24.500 nanomole per liter (nmol/L) | Standard Deviation 11.176 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I (IGF-1) Levels | Week 8 (n = 49, 8) | 27.075 nanomole per liter (nmol/L) | Standard Deviation 6.815 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I (IGF-1) Levels | Week 13 (n = 46, 8) | 26.413 nanomole per liter (nmol/L) | Standard Deviation 8.767 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I (IGF-1) Levels | Week 18 (n = 31, 4) | 25.650 nanomole per liter (nmol/L) | Standard Deviation 8.502 |
Secondary
Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS)
Insulin-like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) was provided by the central laboratory; its calculation is based on the actual value of IGF-1 minus mean reference value of IGF-1 divided by reference standard deviation of IGF-1.
Time frame: Baseline, Week 2, Week 4, Week 8, Week 13, Week 18, Week 26
Population: Safety population consisted of all the participants who received at least 1 dose of study medication and had at least one post-baseline safety assessment. 'N' (number of participants analyzed) = participants who were evaluated for this measure and n= participants who were analyzed at that particular time point for each arm group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Saizen® | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 4 (n = 49, 8) | -0.867 standard deviation score | Standard Deviation 2.615 |
| Saizen® | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 13 (n = 46, 8) | 0.212 standard deviation score | Standard Deviation 1.832 |
| Saizen® | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 2 (n = 47, 8) | -0.926 standard deviation score | Standard Deviation 2.3 |
| Saizen® | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 18 (n = 31, 4) | 0.455 standard deviation score | Standard Deviation 1.816 |
| Saizen® | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 8 (n = 49, 8) | -0.464 standard deviation score | Standard Deviation 2.274 |
| Saizen® | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 26 (n = 48, 8) | 0.167 standard deviation score | Standard Deviation 2.016 |
| Saizen® | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Baseline (n = 49, 8) | -2.914 standard deviation score | Standard Deviation 2.268 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 26 (n = 48, 8) | 0.544 standard deviation score | Standard Deviation 1.894 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Baseline (n = 49, 8) | -0.550 standard deviation score | Standard Deviation 2.274 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 2 (n = 47, 8) | 0.951 standard deviation score | Standard Deviation 1.411 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 4 (n = 49, 8) | 0.153 standard deviation score | Standard Deviation 1.762 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 8 (n = 49, 8) | 0.834 standard deviation score | Standard Deviation 1.063 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 13 (n = 46, 8) | 0.666 standard deviation score | Standard Deviation 1.225 |
| GH Treatment-Experienced | Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS) | Week 18 (n = 31, 4) | 1.043 standard deviation score | Standard Deviation 1.144 |
Secondary
Number of Participants Who Developed Positive Neutralizing Antibodies (NAbs+) to Saizen®
Neutralizing antibodies (NAbs) are defined as a subgroup of BAbs which bind to the active sites of the investigational drug molecule (Saizen®) and therefore neutralize its potency.
Time frame: Baseline up to Week 26
Population: MITT population consisted of all the participants who received at least 1 dose of study medication and had at least one post-baseline BAbs assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saizen® | Number of Participants Who Developed Positive Neutralizing Antibodies (NAbs+) to Saizen® | 0 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse events (AEs): Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications. TEAEs: AEs occurring after the first administration of Saizen® solution for injection (on Day 1) up to the scheduled routine post treatment follow-up visit (4 weeks \[28 days\] after the final administration of Saizen® solution for injection).
Time frame: Day 1 up to 28 days after last dose of study treatment
Population: Safety population consisted of all the participants who received at least 1 dose of study medication and had at least one post-baseline safety assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saizen® | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 40 participants |