Trial Outcomes & Findings for Saizen® Solution for Injection Adult Growth Hormone Deficiency (GHD) Immunogenicity Study (NCT NCT01237340)
NCT ID: NCT01237340
Last Updated: 2013-08-07
Results Overview
Binding antibodies (BAbs) are all antibodies which are capable of binding to the investigational drug molecule (Saizen®), irrespective of their binding site.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
59 participants
Primary outcome timeframe
Baseline up to Week 26
Results posted on
2013-08-07
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
59
|
|
Overall Study
COMPLETED
|
19
|
|
Overall Study
NOT COMPLETED
|
40
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Early termination of the trial
|
36
|
Baseline Characteristics
Saizen® Solution for Injection Adult Growth Hormone Deficiency (GHD) Immunogenicity Study
Baseline characteristics by cohort
| Measure |
Saizen®
n=59 Participants
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.
|
|---|---|
|
Age Continuous
|
44.7 years
STANDARD_DEVIATION 10.3 • n=93 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 26Population: 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.
Binding antibodies (BAbs) are all antibodies which are capable of binding to the investigational drug molecule (Saizen®), irrespective of their binding site.
Outcome measures
| Measure |
Saizen®
n=59 Participants
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.
|
GH Treatment-Experienced
Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. 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.
|
|---|---|---|
|
Number of Participants Who Developed Positive Binding Antibodies (BAbs+) to Saizen®
|
1 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 26Population: 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.
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.
Outcome measures
| Measure |
Saizen®
n=59 Participants
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.
|
GH Treatment-Experienced
Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. 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.
|
|---|---|---|
|
Number of Participants Who Developed Positive Neutralizing Antibodies (NAbs+) to Saizen®
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 13, Week 18, Week 26Population: 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.
Outcome measures
| Measure |
Saizen®
n=49 Participants
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.
|
GH Treatment-Experienced
n=8 Participants
Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. 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.
|
|---|---|---|
|
Insulin-like Growth Factor-I (IGF-1) Levels
Baseline (n = 49, 8)
|
11.492 nanomole per liter (nmol/L)
Standard Deviation 6.694
|
20.225 nanomole per liter (nmol/L)
Standard Deviation 10.194
|
|
Insulin-like Growth Factor-I (IGF-1) Levels
Week 2 (n = 47, 8)
|
18.923 nanomole per liter (nmol/L)
Standard Deviation 10.394
|
28.663 nanomole per liter (nmol/L)
Standard Deviation 9.001
|
|
Insulin-like Growth Factor-I (IGF-1) Levels
Week 4 (n = 49, 8)
|
19.914 nanomole per liter (nmol/L)
Standard Deviation 11.532
|
24.500 nanomole per liter (nmol/L)
Standard Deviation 11.176
|
|
Insulin-like Growth Factor-I (IGF-1) Levels
Week 8 (n = 49, 8)
|
21.155 nanomole per liter (nmol/L)
Standard Deviation 10.520
|
27.075 nanomole per liter (nmol/L)
Standard Deviation 6.815
|
|
Insulin-like Growth Factor-I (IGF-1) Levels
Week 13 (n = 46, 8)
|
23.415 nanomole per liter (nmol/L)
Standard Deviation 8.020
|
26.413 nanomole per liter (nmol/L)
Standard Deviation 8.767
|
|
Insulin-like Growth Factor-I (IGF-1) Levels
Week 18 (n = 31, 4)
|
24.948 nanomole per liter (nmol/L)
Standard Deviation 9.300
|
25.650 nanomole per liter (nmol/L)
Standard Deviation 8.502
|
|
Insulin-like Growth Factor-I (IGF-1) Levels
Week 26 (n = 48, 8)
|
24.117 nanomole per liter (nmol/L)
Standard Deviation 11.085
|
27.438 nanomole per liter (nmol/L)
Standard Deviation 12.402
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 13, Week 18, Week 26Population: 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.
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.
Outcome measures
| Measure |
Saizen®
n=49 Participants
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.
|
GH Treatment-Experienced
n=8 Participants
Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. 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.
|
|---|---|---|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS)
Baseline (n = 49, 8)
|
-2.914 standard deviation score
Standard Deviation 2.268
|
-0.550 standard deviation score
Standard Deviation 2.274
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-1 SDS)
Week 2 (n = 47, 8)
|
-0.926 standard deviation score
Standard Deviation 2.300
|
0.951 standard deviation score
Standard Deviation 1.411
|
|
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
|
0.153 standard deviation score
Standard Deviation 1.762
|
|
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
|
0.834 standard deviation score
Standard Deviation 1.063
|
|
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
|
0.666 standard deviation score
Standard Deviation 1.225
|
|
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
|
1.043 standard deviation score
Standard Deviation 1.144
|
|
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
|
0.544 standard deviation score
Standard Deviation 1.894
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 8, Week 13, Week 18, Week 26Population: 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.
Outcome measures
| Measure |
Saizen®
n=51 Participants
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.
|
GH Treatment-Experienced
n=8 Participants
Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. 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.
|
|---|---|---|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Baseline (n = 51, 8)
|
124.941 nmol/L
Standard Deviation 31.899
|
133.375 nmol/L
Standard Deviation 36.024
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Week 2 (n = 49, 8)
|
137.408 nmol/L
Standard Deviation 35.088
|
162.125 nmol/L
Standard Deviation 35.203
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Week 4 (n = 49, 8)
|
144.592 nmol/L
Standard Deviation 32.632
|
147.750 nmol/L
Standard Deviation 26.451
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Week 8 (n = 50, 8)
|
147.460 nmol/L
Standard Deviation 36.381
|
156.625 nmol/L
Standard Deviation 36.190
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Week 13 (n = 47, 8)
|
149.404 nmol/L
Standard Deviation 28.272
|
151.875 nmol/L
Standard Deviation 35.679
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Week 18 (n = 32, 4)
|
148.813 nmol/L
Standard Deviation 39.754
|
155.500 nmol/L
Standard Deviation 36.235
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Week 26 (n = 49, 8)
|
152.429 nmol/L
Standard Deviation 35.649
|
147.500 nmol/L
Standard Deviation 30.402
|
SECONDARY outcome
Timeframe: Day 1 up to 28 days after last dose of study treatmentPopulation: 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.
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).
Outcome measures
| Measure |
Saizen®
n=59 Participants
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.
|
GH Treatment-Experienced
Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. Growth hormone (GH) Treatment-experienced participants were those who had undergone treatment with the freeze-dried formulation of Saizen® before initiation of the trial. 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.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
|
40 participants
|
—
|
Adverse Events
Saizen®
Serious events: 3 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Saizen®
n=59 participants at risk
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.
|
|---|---|
|
Psychiatric disorders
Anxiety
|
1.7%
1/59 • Day 1 up to 28 days after last dose of study treatment
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).
|
|
Psychiatric disorders
Depression
|
1.7%
1/59 • Day 1 up to 28 days after last dose of study treatment
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).
|
|
Investigations
Hepatic enzyme increased
|
1.7%
1/59 • Day 1 up to 28 days after last dose of study treatment
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).
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.7%
1/59 • Day 1 up to 28 days after last dose of study treatment
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).
|
Other adverse events
| Measure |
Saizen®
n=59 participants at risk
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.
|
|---|---|
|
General disorders
Oedema peripheral
|
8.5%
5/59 • Day 1 up to 28 days after last dose of study treatment
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).
|
|
Infections and infestations
Nasopharyngitis
|
6.8%
4/59 • Day 1 up to 28 days after last dose of study treatment
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).
|
|
Nervous system disorders
Headache
|
5.1%
3/59 • Day 1 up to 28 days after last dose of study treatment
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).
|
|
Investigations
Insulin-like growth factor increased
|
5.1%
3/59 • Day 1 up to 28 days after last dose of study treatment
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).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.1%
3/59 • Day 1 up to 28 days after last dose of study treatment
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).
|
Additional Information
Merck KGaA Communication Center
Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER