Adult Growth Hormone Deficiency, Growth Hormone Disorder
Conditions
Brief summary
This trial is conducted in Europe and Asia. The aim of the trial is to compare the safety of once weekly dosing of somapacitan (administered with an investigational pen) with daily Norditropin® FlexPro® (somatropin delivered within a prefilled pen) for 26 weeks in previously human growth hormone (hGH) treated adults with growth hormone deficiency.
Interventions
DRUGsomapacitan
Administered subcutaneously (s.c., under the skin) with an investigational pen once weekly for a 26 week period (8 weeks' dose titration, 18 weeks' fixed dose treatment) followed by 1 week washout.
DRUGsomatropin
Administered subcutaneously (s.c., under the skin) with a prefilled pen (Norditropin® FlexPro®) daily for a 26 week period (8 weeks' dose titration, 18 weeks' fixed dose treatment) followed by 1 week washout.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
- Male or female of at least 18 years of age and not more than 79 years of age at the time of signing informed consent - Adult growth hormone deficiency diagnosed for 6 months or longer (defined as 180 days) prior to screening - Treatment with hGH (human growth hormone) for at least 6 months at screening - If applicable, hormone replacement therapies for any other hormone deficiencies, adequate and stable for at least 90 days prior to randomisation as judged by the investigator
Exclusion criteria
- Active malignant disease or history of malignancy. Exceptions to this exclusion criterion: Resected in situ carcinoma of the cervix and squamous cell or basal cell carcinoma of the skin with complete local excision. / Subjects with GHD (growth hormone deficiency) attributed to treatment of intracranial malignant tumours or leukaemia, provided that a recurrence-free survival period of at least 5 years is documented in the subject's file - For patients with surgical removal or debulking of pituitary adenoma or other benign intracranial tumour within the last 5 years: Evidence of growth of pituitary adenoma or other benign intracranial tumour within the last 12 months (defined as below or equal to 365 days) before randomisation. Absence of growth must be documented by two post-surgery MRI or CT scans. The most recent MRI or CT scan must be performed below or equal to 9 months (defined as below or equal to 270 days) prior to randomisation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Weeks 0 - 26 | An adverse event can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. Presented results are event rate per 100 patient years of exposure. |
| Incidence of Injection Site Reactions | Weeks 0- 26 | Presented results are event (injection site reaction) rate per 100 patient years of exposure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Anti-NNC0195-0092 Antibodies | At week 0 (baseline), and at week 2, 4, 8, 16, 25 and 27 | Number of participants with anti-somapacitan (NNC0195-0092) antibodies are presented. |
| Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores) | Baseline (week 0), week 26 | The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. Items are rated on a 5 or 7-point scale according to participants' experience with the medication. Each domain score can vary from 0 to 100 with higher scores indicating higher effectiveness of treatment, more convenient use of medication and overall greater satisfaction with the treatment. |
Countries
Denmark, France, Germany, Japan, Sweden, United Kingdom
Participant flow
Recruitment details
The trial was conducted at 26 sites in 6 countries. All 26 sites screened and randomised/ assigned patients to treatment. Denmark: 3 sites; France: 5 sites; Germany: 3 sites; Sweden: 3 sites; United Kingdom: 5 sites; Japan: 7 sites.
Pre-assignment details
Participants, who were diagnosed with adults with growth hormone deficiency ≥ 6 months (defined as 180 days) prior to screening and receiving treatment with human growth hormone at least 6 months (defined as 180 days) at screening, were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Norditropin Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:
IGF-I SDS \> 3: dose reduction by 0.1 mg/day 2 \< IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 \< IGF-I SDS ≤ 2: No need of dose adjustment
* 2 \< IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg). | 31 |
| Somapacitan Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:
IGF-I SDS \> 3: dose reduction by 1 mg 2 \< IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 \< IGF-I SDS ≤ 2: No need for dose adjustment
* 2 \< IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg. | 61 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Norditropin | Somapacitan | Total |
|---|---|---|---|
| Age, Continuous | 51.7 years STANDARD_DEVIATION 17.1 | 48.1 years STANDARD_DEVIATION 16.2 | 49.3 years STANDARD_DEVIATION 16.5 |
| Age, Customized 18-64 years | 23 Participants | 50 Participants | 73 Participants |
| Age, Customized ≥65 years | 8 Participants | 11 Participants | 19 Participants |
| Sex: Female, Male Female | 14 Participants | 28 Participants | 42 Participants |
| Sex: Female, Male Male | 17 Participants | 33 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 31 | 30 / 61 |
| serious Total, serious adverse events | 2 / 31 | 4 / 61 |
Outcome results
Primary
Incidence of Adverse Events
An adverse event can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. Presented results are event rate per 100 patient years of exposure.
Time frame: Weeks 0 - 26
Population: Safety analysis set: all randomised participants that received at least one dose of randomised treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Norditropin | Incidence of Adverse Events | 530.8 Events per 100 patient years |
| Somapacitan | Incidence of Adverse Events | 514.2 Events per 100 patient years |
Primary
Incidence of Injection Site Reactions
Presented results are event (injection site reaction) rate per 100 patient years of exposure.
Time frame: Weeks 0- 26
Population: Safety analysis set: all randomised participants that received at least one dose of randomised treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Norditropin | Incidence of Injection Site Reactions | 0 Events per 100 patient years |
| Somapacitan | Incidence of Injection Site Reactions | 6.5 Events per 100 patient years |
Secondary
Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores)
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. Items are rated on a 5 or 7-point scale according to participants' experience with the medication. Each domain score can vary from 0 to 100 with higher scores indicating higher effectiveness of treatment, more convenient use of medication and overall greater satisfaction with the treatment.
Time frame: Baseline (week 0), week 26
Population: Overall Number of Participants Analyzed = full analysis set which included all randomised participants that received at least one dose of randomised treatment. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Norditropin | Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores) | Effectiveness | 3.8 Score on a scale | Standard Deviation 27.4 |
| Norditropin | Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores) | Convenience | 3.0 Score on a scale | Standard Deviation 16.5 |
| Norditropin | Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores) | Global satisfaction | -1.2 Score on a scale | Standard Deviation 15.2 |
| Somapacitan | Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores) | Convenience | 15.3 Score on a scale | Standard Deviation 20.9 |
| Somapacitan | Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores) | Global satisfaction | 5.4 Score on a scale | Standard Deviation 21 |
| Somapacitan | Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores) | Effectiveness | 9.7 Score on a scale | Standard Deviation 18.1 |
Secondary
Occurrence of Anti-NNC0195-0092 Antibodies
Number of participants with anti-somapacitan (NNC0195-0092) antibodies are presented.
Time frame: At week 0 (baseline), and at week 2, 4, 8, 16, 25 and 27
Population: Overall Number of Participants Analyzed = safety analysis set which included all randomised participants that received at least one dose of randomised treatment. Number Analyzed = number of participants with available data. This outcome measure is applicable only for the somapacitan treatment arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Norditropin | Occurrence of Anti-NNC0195-0092 Antibodies | Week 0: | 0 Participants |
| Norditropin | Occurrence of Anti-NNC0195-0092 Antibodies | Week 2: | 0 Participants |
| Norditropin | Occurrence of Anti-NNC0195-0092 Antibodies | Week 4: | 0 Participants |
| Norditropin | Occurrence of Anti-NNC0195-0092 Antibodies | Week 8: | 0 Participants |
| Norditropin | Occurrence of Anti-NNC0195-0092 Antibodies | Week 16: | 0 Participants |
| Norditropin | Occurrence of Anti-NNC0195-0092 Antibodies | Week 25: | 0 Participants |
| Norditropin | Occurrence of Anti-NNC0195-0092 Antibodies | Week 27: | 0 Participants |