An Open-label Phase 4 Study to Explore Immunogenicity of the Liquid Formulation of Saizen® in Subjects With Adult Growth Hormone Deficiency (AGHD)
Condition: Adult Growth Hormone Deficiency
MeSH terms: Dwarfism, Pituitary; Endocrine System Diseases
Intervention: Saizen® solution for injection (referred as Saizen®)
Intervention description: 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 MeSH terms: Hormones
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Adult Growth hormone deficiency; Saizen®; Recombinant human growth hormone (r-hGH); Somatropin

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.
    

Eligibility criteria:

        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

        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