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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01806298




Registration number
NCT01806298
Ethics application status
Date submitted
5/03/2013
Date registered
7/03/2013
Date last updated
2/12/2017

Titles & IDs
Public title
An Open-label Phase 4 Study to Explore Immunogenicity of the Liquid Formulation of Saizen® in Subjects With Adult Growth Hormone Deficiency (AGHD)
Scientific 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)
Secondary ID [1] 0 0
2012-004263-47
Secondary ID [2] 0 0
EMR 200104-011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adult Growth Hormone Deficiency 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Saizen® solution for injection (referred as Saizen®)

Experimental: Saizen® -


Treatment: Drugs: Saizen® solution for injection (referred as Saizen®)
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®.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline up to Week 39
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline up to Week 39
Secondary outcome [2] 0 0
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]).
Timepoint [2] 0 0
Baseline, Week 2, 8, 16, 29, 39 and 41
Secondary outcome [3] 0 0
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])
Timepoint [3] 0 0
Baseline, Week 2, 8, 16, 29, 39 and 41
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline, Week 2, 8, 16, 29, 39 and 41
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Week 2, 8, 16, 29 and 39

Eligibility
Key inclusion criteria
- 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).

- 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
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 0 0
Research site - Adelaide
Recruitment hospital [2] 0 0
Research site - Perth
Recruitment hospital [3] 0 0
Research site - Clayton
Recruitment hospital [4] 0 0
Research site - Darlinghurst
Recruitment hospital [5] 0 0
Research site - Fitzroy
Recruitment postcode(s) [1] 0 0
5041 - Adelaide
Recruitment postcode(s) [2] 0 0
6009 - Perth
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Berlin
Country [2] 0 0
Germany
State/province [2] 0 0
Oldenburg
Country [3] 0 0
Germany
State/province [3] 0 0
Würzburg
Country [4] 0 0
Sweden
State/province [4] 0 0
Goteborg
Country [5] 0 0
Sweden
State/province [5] 0 0
Stockholm
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Birmingham
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Cleveland
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Guildford
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Liverpool
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Manchester
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Norfolk
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Oxford
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck KGaA, Darmstadt, Germany
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 Screening and have no contraindication to the use of GH.
Trial website
https://clinicaltrials.gov/show/NCT01806298
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications