Adult Growth Hormone DeficiencyPhase 4NCT01806298
An Open-label Phase 4 Study to Explore Immunogenicity of the Liquid Formulation of Saizen® in Subjects With Adult Growth Hormone Deficiency (AGHD)
A Phase 4 study testing Saizen® solution for injection (referred as Saizen®) in people with Adult Growth Hormone Deficiency, run by Merck KGaA, Darmstadt, Germany at 19 sites in 4 countries.
Trial summary
This is an open-label, single-arm, multicenter, Phase 4 study to explore the immunogenicity of the liquid formulation of Saizen® in subjects with Adult Growth Hormone Deficiency (AGHD), who are growth hormone (GH) treatment-naïve or who had prior GH treatment for GHD which was stopped at least 1 month prior to… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Adult Growth Hormone Deficiency
- What is being tested?
- Saizen® solution for injection (referred as Saizen®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 19 sitesin 4 countries
- Study dates
- Jun 2013to Mar 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects, 18-65 years of age, inclusive, at the time of signature of informed consent
- Documented AGHD i.e. childhood onset (CO) or adult onset (AO), either by a stimulation test as described in the GH Research Society's 2007 guidelines for the diagnosis and treatment of AGHD, or in the Saizen® label, whichever is more stringent, or by confirming the presence of at least 3 pituitary hormone deficiencies and an IGF-1 level below the reference range of the laboratory where testing is performed. Stimulation test as described in the 2007 GH Research Society guidelines and applicable to all subjects who underwent or will undergo a stimulation test:
- Insulin Tolerance Test (ITT) or glucagon stimulation test: Peak GH less than 3 nanogram per milliliter (ng/mL);
- GH-releasing hormone (GHRH) plus arginine test, peak GH depends on body mass index (BMI):
- BMI less than 25 kilogram per square meter (kg/m^2) indicates a peak GH less than 11 ng/mL microgram per liter [mcg/L]).
- BMI 25-30 kg/m^2 indicates a peak GH less than 8 ng/mL (mcgg/L).
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- BMI greater than 30 kg/m^2 indicates a peak GH less than 4 ng/mL (mcg/L).
- Clonidine, l-dopa, and arginine alone are not acceptable as stimulation tests for determining eligibility in this trial. Stimulation tests remain under the Investigator's or the subject's physician's responsibility, including the selection of the GH assay. Saizen® label: in Europe, only one single test is required; in Australia, 2 stimulation tests showing a peak GH less than 2.5 ng/mL are required. The inclusion criteria were chosen based on the approved label for Saizen® in the countries where the trial is being implemented, as well as in respect of the most current international guidelines for AGHD. There is no limit in time prior to the Screening visit for the stimulation test(s), as long as documentation is available and the stimulation tests comply with the GH Research Society 2007 guidelines, and as such, there is no need to repeat the test for subjects having stopped their GH therapy prior to the Screening visit. No stimulation test is required for subjects with 3 or more pituitary hormone deficiencies
- GH treatment-naïve or prior GH treatment for AGHD stopped at least 1 month prior to Screening visit. Whereas any prior use of GH is permitted, providing an adequate wash-out period is respected to secure the interpretation of the biomarkers, the reason for stopping the GH therapy should neither be safety- nor efficacy-related, and documentation should be present in the source information
- Negative BAbs from the Screening visit sample
- Body mass index (BMI, Weight in kilograms / Height in square meters) measured at Screening visit as less than or equal to 35 kilogram per square meter (kg/m^2)
- Negative serum pregnancy test at the Screening for women of childbearing potential and subject is not lactating
- Understanding and willingness of the subject to comply with the procedures of the study
- Informed Consent form signed prior to the performance of any trial-related activities
Who cannot join
- Hypersensitivity to the active substance or to any of the Saizen® excipients
- Evidence of growing intracranial tumor including pituitary tumor, or affecting the optic chiasm, or requiring treatment (surgery or radiation) within the 6 months prior to and the 12 months after the Screening visit
- Presence of active malignancy, neoplasia or any evidence of progression or recurrence of an underlying tumor. In case of a history of neoplasia or any pre-existing malignancy, the tumor must be inactive and anti-tumor therapy completed prior to starting trial on active Saizen® therapy.
- Proliferative or pre-proliferative diabetic retinopathy
- Evidence of chronic underlying disease within 6 months prior to the Screening visit or concomitant medication that would interfere with subject compliance, the evaluation of trial results, or compromise the safety of the subject
- Severe hepatic or renal failure that could compromise the interpretation of IGF-1, that is: Alanine transaminase [ALT] or aspartate transaminase [AST] greater than 3 * upper limit of the normal range; Glomerular filtration rate (GFR) less than 30 milliliter per minute (mL/min) Note: GFR will be calculated by the laboratory according to the Modification of Diet in Renal Disease (MDRD) equation
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- History of anti-GH antibodies
- History or presence of an autoimmune disease, such as Hashimoto's disease or Systemic Lupus Erythematosus (SLE), immunosuppression regardless of etiology, or GH1 gene defect
- Absence of effective contraception in place at the Screening visit in women of childbearing potential. Acceptable forms of effective contraception include: established use of oral (greater than 2 months), injected, or implanted hormonal methods of contraception, intrauterine devices (IUD), or barrier methods of contraception, specifically, condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
- Diabetes mellitus (per American Diabetes Association 2010 guidelines): either i) standard diabetes symptoms and a random glucose greater than or equal to 200 milligram per deciliter (mg/dL) (11.1 millimolar per liter [mmol/L]); ii) a fasting plasma glucose greater than 126 mg/dL (6.99 mmol/L); iii) a 2-hour plasma glucose greater than or equal to 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT); or iv) an glycosylated hemoglobin (HbA1c) greater than or equal to 6.5 percent
- Concomitant or prior participation in an interventional trial within 30 days prior to the Screening visit
- Known alcohol or drug addiction/dependency
- Has a legal incapacity or limited legal capacity
- Has received anabolic steroids (except for gonadal steroid replacement therapy) or systemic corticosteroids (except for replacement doses) within 3 months prior to the Screening visit
- Has received substitutive therapy with glucocorticosteroids, thyroid replacement, vasopressin, or sex hormones for less than 3 months or substitutive therapy has not been stable (that is, dose was not generally constant or medical condition was not controlled) for 3 months prior to Screening
Trial locations and contacts
19 sites in 4 countries.
19 sites in 4 countries
United Kingdom9 sites
Research site
Birmingham
Research site
Cleveland, TS4 3BW
Research site
Guildford, GU2 7XX
Research site
Liverpool, L69 3PX
Research site
Manchester, M20 4BX
Research site
Manchester, M6 8HD
Research site
Norfolk, PE30 4ET
Research site
Oxford, OX3 7LJ
Research site
Truro, TR1 3LJ
Australia5 sites
Research site
Adelaide, South Australia, 5041
Research site
Clayton, 3168
Research site
Darlinghurst, 2010
Research site
Fitzroy, 3065
Research site
Perth, Western Australia, 6009
Germany3 sites
Research site
Berlin, 13344
Research site
Oldenburg, 26122
Research site
Würzburg, 97080
About this study
Official title: Open-label, Single-arm, Phase IV, Multicenter Trial to Explore the Immunogenicity of the Liquid Formulation of Saizen® in Subjects With Adult Growth Hormone Deficiency (AGHD)
This is an open-label, single-arm, multicenter, Phase 4 study to explore the immunogenicity of the liquid formulation of Saizen® in subjects with Adult Growth Hormone Deficiency (AGHD), who are growth hormone (GH) treatment-naïve or who had prior GH treatment for GHD which was stopped at least 1 month prior to Screening and have no contraindication to the use of GH.
- Conditions
- Adult Growth Hormone Deficiency
- Being tested
- Saizen® solution for injection (referred as Saizen®)
- Keywords
- Adult Growth hormone deficiency, Saizen®, Recombinant human growth hormone (r-hGH), Somatropin
- Medical subject headings
- Dwarfism, Pituitary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saizen® solution for injection (referred as Saizen®)Drug
Also called Somatropin, Recombinant human growth hormone (r-hGH)
Saizen® solution for injection will be administered subcutaneously daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®.
| Study group | Role | What they receive |
|---|---|---|
| Saizen® | Experimental | Not described Receives: Drug: Saizen® solution for injection (referred as Saizen®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects Developing Binding Antibodies (BAbs) to Saizen®
Percentage of subjects developing BAbs = (Number of BAb positive subjects / Total number of subjects) x 100.
Measured: Baseline up to Week 39
Secondary outcomes (5)
Percentage of Subjects With Binding Antibodies (BAbs) Who Became Positive for Neutralizing Antibodies (NAbs)
Percentage of subjects with BAbs who become positive for NAbs = (Number of NAb positive subjects / Number of BAbs positive subjects) x 100
Measured: Baseline up to Week 39
Insulin-like Growth Factor-I (IGF-I) Levels
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]).
Measured: Baseline, Week 2, 8, 16, 29, 39 and 41
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
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])
Measured: Baseline, Week 2, 8, 16, 29, 39 and 41
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
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.
Measured: Baseline, Week 2, 8, 16, 29, 39 and 41
Treatment Adherence Rate as Documented Using EasypodTM Connect
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.
Measured: Week 2, 8, 16, 29 and 39
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2013 (estimated)
- Study startJun 2013
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Growth Hormone DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01806298
- Sponsor's protocol ID
- EMR 200104-011
- Other IDs
- 2012-004263-47
- Status last verified
- Oct 2017
- First submitted
- 5 Mar 2013
- Last updated
- 2 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Single-arm, Phase IV, Multicenter Trial to Explore the Immunogenicity of the Liquid Formulation of Saizen® in Subjects With Adult Growth Hormone Deficiency (AGHD)
- ClinicalTrials.gov ID
- NCT01806298
- Acronym / sponsor ID
- EMR 200104-011
- Conditions
- Adult Growth Hormone Deficiency
- Keywords
- Adult Growth hormone deficiency, Saizen®, Recombinant human growth hormone (r-hGH), Somatropin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 7 Mar 2013 (estimated)
- Results
- Posted 4 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, single-arm, multicenter, Phase 4 study to explore the immunogenicity of the liquid formulation of Saizen® in subjects with Adult Growth Hormone Deficiency (AGHD), who are growth hormone (GH) treatment-naïve or who had prior GH treatment for GHD which was stopped at least 1 month prior to Screening and have no contraindication to the use of GH.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Saizen® | Experimental | Drug: Saizen® solution for injection (referred as Saizen®) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male and female subjects, 18-65 years of age, inclusive, at the time of signature of informed consent
- Documented AGHD i.e. childhood onset (CO) or adult onset (AO), either by a stimulation test as described in the GH Research Society's 2007 guidelines for the diagnosis and treatment of AGHD, or in the Saizen® label, whichever is more stringent, or by confirming the presence of at least 3 pituitary hormone deficiencies and an IGF-1 level below the reference range of the laboratory where testing is performed. Stimulation test as described in the 2007 GH Research Society guidelines and applicable to all subjects who underwent or will undergo a stimulation test:
- Clonidine, l-dopa, and arginine alone are not acceptable as stimulation tests for determining eligibility in this trial. Stimulation tests remain under the Investigator's or the subject's physician's responsibility, including the selection of the GH assay. Saizen® label: in Europe, only one single test is required; in Australia, 2 stimulation tests showing a peak GH less than 2.5 ng/mL are required. The inclusion criteria were chosen based on the approved label for Saizen® in the countries where the trial is being implemented, as well as in respect of the most current international guidelines for AGHD. There is no limit in time prior to the Screening visit for the stimulation test(s), as long as documentation is available and the stimulation tests comply with the GH Research Society 2007 guidelines, and as such, there is no need to repeat the test for subjects having stopped their GH therapy prior to the Screening visit. No stimulation test is required for subjects with 3 or more pituitary hormone deficiencies
- GH treatment-naïve or prior GH treatment for AGHD stopped at least 1 month prior to Screening visit. Whereas any prior use of GH is permitted, providing an adequate wash-out period is respected to secure the interpretation of the biomarkers, the reason for stopping the GH therapy should neither be safety- nor efficacy-related, and documentation should be present in the source information
- Negative BAbs from the Screening visit sample
Key exclusion criteria (15 listed)
- Hypersensitivity to the active substance or to any of the Saizen® excipients
- Evidence of growing intracranial tumor including pituitary tumor, or affecting the optic chiasm, or requiring treatment (surgery or radiation) within the 6 months prior to and the 12 months after the Screening visit
- Presence of active malignancy, neoplasia or any evidence of progression or recurrence of an underlying tumor. In case of a history of neoplasia or any pre-existing malignancy, the tumor must be inactive and anti-tumor therapy completed prior to starting trial on active Saizen® therapy.
- Proliferative or pre-proliferative diabetic retinopathy
- Evidence of chronic underlying disease within 6 months prior to the Screening visit or concomitant medication that would interfere with subject compliance, the evaluation of trial results, or compromise the safety of the subject
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Saizen® solution for injection (referred as Saizen®)Also: Somatropin, Recombinant human growth hormone (r-hGH)Saizen® solution for injection will be administered subcutaneously daily for 39 weeks according to locally approved product labeling for the currently marketed formulation of Saizen®. | Drug | Saizen® |
Primary outcome
Percentage of Subjects Developing Binding Antibodies (BAbs) to Saizen®
Time frame: Baseline up to Week 39
Percentage of subjects developing BAbs = (Number of BAb positive subjects / Total number of subjects) x 100.
5 secondary outcomes
Percentage of Subjects With Binding Antibodies (BAbs) Who Became Positive for Neutralizing Antibodies (NAbs)
Time frame: Baseline up to Week 39
Insulin-like Growth Factor-I (IGF-I) Levels
Time frame: Baseline, Week 2, 8, 16, 29, 39 and 41
Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Levels
Time frame: Baseline, Week 2, 8, 16, 29, 39 and 41
Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS)
Time frame: Baseline, Week 2, 8, 16, 29, 39 and 41
Treatment Adherence Rate as Documented Using EasypodTM Connect
Time frame: Week 2, 8, 16, 29 and 39
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck KGaA, Darmstadt, Germany
19 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Saizen® solution for injection (referred as Saizen®) in people with Adult Growth Hormone Deficiency, run by Merck KGaA, Darmstadt, Germany at 19 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United Kingdom, Australia, Germany, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Subjects Developing Binding Antibodies (BAbs) to Saizen® (time frame: Baseline up to Week 39). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2017.