Trial Outcomes & Findings for An Open-label Phase 4 Study to Explore Immunogenicity of the Liquid Formulation of Saizen® in Subjects With Adult Growth Hormone Deficiency (AGHD) (NCT NCT01806298)
NCT ID: NCT01806298
Last Updated: 2017-12-02
Results Overview
Percentage of subjects developing BAbs = (Number of BAb positive subjects / Total number of subjects) x 100.
COMPLETED
PHASE4
78 participants
Baseline up to Week 39
2017-12-02
Participant Flow
Participant milestones
| Measure |
Saizen®
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Overall Study
STARTED
|
78
|
|
Overall Study
COMPLETED
|
68
|
|
Overall Study
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
Saizen®
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Protocol Non-compliance
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Other
|
5
|
Baseline Characteristics
An Open-label Phase 4 Study to Explore Immunogenicity of the Liquid Formulation of Saizen® in Subjects With Adult Growth Hormone Deficiency (AGHD)
Baseline characteristics by cohort
| Measure |
Saizen®
n=78 Participants
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Age, Continuous
|
44.5 years
STANDARD_DEVIATION 12.61 • n=5 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 39Population: The modified Intent-To-Treat (mITT) analysis set included all treated subjects who had received at least 1 administration of Saizen® and had at least 1 post-baseline BAbs assessment.
Percentage of subjects developing BAbs = (Number of BAb positive subjects / Total number of subjects) x 100.
Outcome measures
| Measure |
Saizen®
n=77 Participants
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Percentage of Subjects Developing Binding Antibodies (BAbs) to Saizen®
|
0 percentage of subjects
Interval 0.0 to 4.68
|
SECONDARY outcome
Timeframe: Baseline up to Week 39Population: Data could not be analyzed as there were no subjects who were BAb positive.
Percentage of subjects with BAbs who become positive for NAbs = (Number of NAb positive subjects / Number of BAbs positive subjects) x 100
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 2, 8, 16, 29, 39 and 41Population: The safety analysis set included all treated subjects who had received at least 1 administration of Saizen®. Here, "Number Analyzed" signifies those subjects who were evaluable for the specified category at each time point.
Growth Hormone (GH) biomarker levels were summarized by GH treatment status at study entry (that is subjects were classified as GH treatment-naïve subjects or subjects with prior GH treatment for adult growth hormone deficiency \[AGHD\]).
Outcome measures
| Measure |
Saizen®
n=78 Participants
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Insulin-like Growth Factor-I (IGF-I) Levels
GH Treatment-naive: Baseline
|
14.54 nanomoles per liter (nmol/L)
Standard Deviation 7.219
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
Previously took GH treatment : Baseline
|
10.91 nanomoles per liter (nmol/L)
Standard Deviation 4.744
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
GH Treatment-naive: Week 2
|
21.15 nanomoles per liter (nmol/L)
Standard Deviation 9.008
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
Previously took GH treatment: Week 2
|
19.41 nanomoles per liter (nmol/L)
Standard Deviation 5.804
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
GH Treatment-naive: Week 8
|
23.41 nanomoles per liter (nmol/L)
Standard Deviation 9.070
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
Previously took GH treatment: Week 8
|
20.91 nanomoles per liter (nmol/L)
Standard Deviation 5.437
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
GH Treatment-naive: Week 16
|
22.34 nanomoles per liter (nmol/L)
Standard Deviation 6.844
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
Previously took GH treatment: Week 16
|
20.15 nanomoles per liter (nmol/L)
Standard Deviation 7.381
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
GH Treatment-naive: Week 29
|
25.07 nanomoles per liter (nmol/L)
Standard Deviation 8.026
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
Previously took GH treatment: Week 29
|
20.90 nanomoles per liter (nmol/L)
Standard Deviation 6.810
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
GH Treatment-naive: Week 39
|
23.82 nanomoles per liter (nmol/L)
Standard Deviation 7.961
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
Previously took GH treatment: Week 39
|
20.56 nanomoles per liter (nmol/L)
Standard Deviation 8.486
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
GH Treatment-naive: Week 41
|
15.28 nanomoles per liter (nmol/L)
Standard Deviation 6.943
|
|
Insulin-like Growth Factor-I (IGF-I) Levels
Previously took GH treatment: Week 41
|
12.12 nanomoles per liter (nmol/L)
Standard Deviation 4.910
|
SECONDARY outcome
Timeframe: Baseline, Week 2, 8, 16, 29, 39 and 41Population: The safety analysis set included all treated subjects who had received at least 1 administration of Saizen®. Here, "Number Analyzed" signifies those subjects who were evaluable for the specified category at each time point.
Growth Hormone (GH) biomarker levels were summarized by GH treatment status at study entry (that is subjects were classified as GH treatment-naïve subjects or subjects with prior GH treatment for adult growth hormone deficiency \[AGHD\])
Outcome measures
| Measure |
Saizen®
n=78 Participants
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
GH Treatment-naive: Baseline
|
2.62 milligram/liter (mg/L)
Standard Deviation 0.843
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Previously took GH treatment : Baseline
|
2.20 milligram/liter (mg/L)
Standard Deviation 0.680
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
GH Treatment-naive: Week 2
|
3.03 milligram/liter (mg/L)
Standard Deviation 0.872
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Previously took GH treatment: Week 2
|
2.85 milligram/liter (mg/L)
Standard Deviation 0.981
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
GH Treatment-naive: Week 8
|
3.11 milligram/liter (mg/L)
Standard Deviation 0.831
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Previously took GH treatment: Week 8
|
2.77 milligram/liter (mg/L)
Standard Deviation 0.795
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
GH Treatment-naive: Week 16
|
3.15 milligram/liter (mg/L)
Standard Deviation 0.746
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Previously took GH treatment: Week 16
|
2.93 milligram/liter (mg/L)
Standard Deviation 0.746
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
GH Treatment-naive: Week 29
|
3.36 milligram/liter (mg/L)
Standard Deviation 0.737
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Previously took GH treatment: Week 29
|
3.22 milligram/liter (mg/L)
Standard Deviation 0.903
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
GH Treatment-naive: Week 39
|
3.45 milligram/liter (mg/L)
Standard Deviation 0.938
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Previously took GH treatment: Week 39
|
3.03 milligram/liter (mg/L)
Standard Deviation 0.853
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
GH Treatment-naive: Week 41
|
2.91 milligram/liter (mg/L)
Standard Deviation 0.758
|
|
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Previously took GH treatment: Week 41
|
2.63 milligram/liter (mg/L)
Standard Deviation 0.786
|
SECONDARY outcome
Timeframe: Baseline, Week 2, 8, 16, 29, 39 and 41Population: The safety analysis set included all treated subjects who had received at least 1 administration of Saizen®. Here, "Number Analyzed" signifies those subjects who were evaluable for the specified category at each time point.
Insulin-like Growth Factor-1 SDS was calculated based on the actual value of IGF-1 minus reference value of IGF-1 divided by reference standard deviation of IGF-1. SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) a subject's value was relative to the mean of the reference population. The scores were centered around zero. Negative score indicated that the IGF-I value was lower compared to the reference population.
Outcome measures
| Measure |
Saizen®
n=78 Participants
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
GH Treatment-naive: Baseline
|
-3.27 Standard deviation score
Standard Deviation 0.816
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
Previously took GH treatment : Baseline
|
-3.67 Standard deviation score
Standard Deviation 1.223
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
GH Treatment-naive: Week 2
|
-3.10 Standard deviation score
Standard Deviation 0.775
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
Previously took GH treatment: Week 2
|
-3.46 Standard deviation score
Standard Deviation 1.140
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
GH Treatment-naive: Week 8
|
-3.05 Standard deviation score
Standard Deviation 0.769
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
Previously took GH treatment: Week 8
|
-3.16 Standard deviation score
Standard Deviation 0.697
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
GH Treatment-naive: Week 16
|
-3.09 Standard deviation score
Standard Deviation 0.799
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
Previously took GH treatment: Week 16
|
-3.17 Standard deviation score
Standard Deviation 0.652
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
GH Treatment-naive: Week 29
|
-3.01 Standard deviation score
Standard Deviation 0.773
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
Previously took GH treatment: Week 29
|
-3.17 Standard deviation score
Standard Deviation 0.713
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
GH Treatment-naive: Week 39
|
-3.02 Standard deviation score
Standard Deviation 0.780
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
Previously took GH treatment: Week 39
|
-3.44 Standard deviation score
Standard Deviation 1.290
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
GH Treatment-naive: Week 41
|
-3.23 Standard deviation score
Standard Deviation 0.830
|
|
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
Previously took GH treatment: Week 41
|
-3.31 Standard deviation score
Standard Deviation 0.690
|
SECONDARY outcome
Timeframe: Week 2, 8, 16, 29 and 39Population: The safety analysis set included all treated subjects who had received at least 1 administration of Saizen®. Here, "Number Analyzed" signifies those subjects who were evaluable for the specified category at each time point.
Treatment adherence rate was measured by: (total dose received divided by total dose prescribed) multiplied by 100. Saizen solution for injection was administered using the easypod device and treatment adherence information was obtained from the device using the easypod connect software.
Outcome measures
| Measure |
Saizen®
n=78 Participants
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Treatment Adherence Rate as Documented Using EasypodTM Connect
|
89.3 percentage of treatment adherence
Standard Deviation 13.35
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to Week 41Population: The safety analysis set included all treated subjects who had received at least 1 administration of Saizen®.
An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are those events with onset dates occurring during the on-treatment period or if the worsening of an event is during the on-treatment period. TEAEs include both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Saizen®
n=78 Participants
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation
TEAEs
|
72 Participants
|
|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation
Serious TEAEs
|
4 Participants
|
|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation
TEAEs Leading to Death
|
0 Participants
|
|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation
TEAEs Leading to Discontinuation
|
4 Participants
|
Adverse Events
Saizen®
Serious adverse events
| Measure |
Saizen®
n=78 participants at risk
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Infections and infestations
Infection
|
1.3%
1/78 • Baseline up to Week 41
|
|
Infections and infestations
Pneumonia
|
1.3%
1/78 • Baseline up to Week 41
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
1.3%
1/78 • Baseline up to Week 41
|
|
Gastrointestinal disorders
Oesophagitis
|
1.3%
1/78 • Baseline up to Week 41
|
|
General disorders
Non-cardiac chest pain
|
1.3%
1/78 • Baseline up to Week 41
|
Other adverse events
| Measure |
Saizen®
n=78 participants at risk
Saizen® solution for injection was administered subcutaneously once daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
|
|---|---|
|
Nervous system disorders
Headache
|
34.6%
27/78 • Baseline up to Week 41
|
|
Infections and infestations
Nasopharyngitis
|
26.9%
21/78 • Baseline up to Week 41
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
13/78 • Baseline up to Week 41
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.8%
10/78 • Baseline up to Week 41
|
|
General disorders
Fatigue
|
9.0%
7/78 • Baseline up to Week 41
|
|
General disorders
Injection site bruising
|
9.0%
7/78 • Baseline up to Week 41
|
|
Gastrointestinal disorders
Diarrhoea
|
7.7%
6/78 • Baseline up to Week 41
|
|
Infections and infestations
Influenza
|
7.7%
6/78 • Baseline up to Week 41
|
|
Infections and infestations
Upper respiratory tract infection
|
7.7%
6/78 • Baseline up to Week 41
|
|
Infections and infestations
Lower respiratory tract infection
|
6.4%
5/78 • Baseline up to Week 41
|
|
Gastrointestinal disorders
Nausea
|
6.4%
5/78 • Baseline up to Week 41
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.4%
5/78 • Baseline up to Week 41
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.1%
4/78 • Baseline up to Week 41
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.1%
4/78 • Baseline up to Week 41
|
|
Nervous system disorders
Paraesthesia
|
5.1%
4/78 • Baseline up to Week 41
|
|
General disorders
Peripheral swelling
|
5.1%
4/78 • Baseline up to Week 41
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.8%
3/78 • Baseline up to Week 41
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.8%
3/78 • Baseline up to Week 41
|
|
Nervous system disorders
Dizziness
|
3.8%
3/78 • Baseline up to Week 41
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
3.8%
3/78 • Baseline up to Week 41
|
|
Psychiatric disorders
Insomnia
|
3.8%
3/78 • Baseline up to Week 41
|
|
Nervous system disorders
Migraine
|
3.8%
3/78 • Baseline up to Week 41
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
3.8%
3/78 • Baseline up to Week 41
|
|
Immune system disorders
Seasonal allergy
|
3.8%
3/78 • Baseline up to Week 41
|
|
Infections and infestations
Tooth abscess
|
3.8%
3/78 • Baseline up to Week 41
|
|
Infections and infestations
Urinary tract infection
|
3.8%
3/78 • Baseline up to Week 41
|
|
Ear and labyrinth disorders
Vertigo
|
3.8%
3/78 • Baseline up to Week 41
|
|
Infections and infestations
Viral infection
|
3.8%
3/78 • Baseline up to Week 41
|
|
Gastrointestinal disorders
Vomiting
|
3.8%
3/78 • Baseline up to Week 41
|
|
Psychiatric disorders
Anxiety
|
2.6%
2/78 • Baseline up to Week 41
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
2.6%
2/78 • Baseline up to Week 41
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
2.6%
2/78 • Baseline up to Week 41
|
|
General disorders
Chest discomfort
|
2.6%
2/78 • Baseline up to Week 41
|
|
Injury, poisoning and procedural complications
Contusion
|
2.6%
2/78 • Baseline up to Week 41
|
|
Gastrointestinal disorders
Dry mouth
|
2.6%
2/78 • Baseline up to Week 41
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
2.6%
2/78 • Baseline up to Week 41
|
|
Gastrointestinal disorders
Dyspepsia
|
2.6%
2/78 • Baseline up to Week 41
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.6%
2/78 • Baseline up to Week 41
|
|
Skin and subcutaneous tissue disorders
Eczema
|
2.6%
2/78 • Baseline up to Week 41
|
|
Injury, poisoning and procedural complications
Fall
|
2.6%
2/78 • Baseline up to Week 41
|
|
Gastrointestinal disorders
Haemorrhoids
|
2.6%
2/78 • Baseline up to Week 41
|
|
General disorders
Injection site pain
|
2.6%
2/78 • Baseline up to Week 41
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
2.6%
2/78 • Baseline up to Week 41
|
|
Nervous system disorders
Lethargy
|
2.6%
2/78 • Baseline up to Week 41
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.6%
2/78 • Baseline up to Week 41
|
|
General disorders
Non-cardiac chest pain
|
2.6%
2/78 • Baseline up to Week 41
|
|
General disorders
Oedema peripheral
|
2.6%
2/78 • Baseline up to Week 41
|
|
General disorders
Pyrexia
|
2.6%
2/78 • Baseline up to Week 41
|
|
Infections and infestations
Sinusitis
|
2.6%
2/78 • Baseline up to Week 41
|
|
Ear and labyrinth disorders
Tinnitus
|
2.6%
2/78 • Baseline up to Week 41
|
|
Gastrointestinal disorders
Toothache
|
2.6%
2/78 • Baseline up to Week 41
|
Additional Information
Merck KGaA Communication Center
Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place