An Open-label Phase 4 Study to Explore Immunogenicity of the Liquid Formulation of Saizen® in Subjects With Adult Growth Hormone Deficiency (AGHD)

NCT ID: NCT01806298

Last Updated: 2017-12-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2016-03-31

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.

Conditions

Adult Growth Hormone Deficiency

Keywords

Adult Growth hormone deficiency; Saizen®; Recombinant human growth hormone (r-hGH); Somatropin

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Saizen®

Group Type: EXPERIMENTAL

Saizen® solution for injection (referred as Saizen®)

Intervention Type: DRUG

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®.

Interventions

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 Type: DRUG

Other Intervention Names

Somatropin; Recombinant human growth hormone (r-hGH)

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).

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Research site

Adelaide, South Australia, Australia

Research site

Perth, Western Australia, Australia

Research site

Clayton, , Australia

Research site

Darlinghurst, , Australia

Research site

Fitzroy, , Australia

Research site

Berlin, , Germany

Research site

Oldenburg, , Germany

Research site

Würzburg, , Germany

Research site

Gothenburg, , Sweden

Research site

Stockholm, , Sweden

Research site

Birmingham, , United Kingdom

Research site

Cleveland, , United Kingdom

Research site

Guildford, , United Kingdom

Research site

Liverpool, , United Kingdom

Research site

Manchester, , United Kingdom

Research site

Manchester, , United Kingdom

Research site

Norfolk, , United Kingdom

Research site

Oxford, , United Kingdom

Research site

Truro, , United Kingdom

Countries

Czechia; Australia; Germany; Sweden; United Kingdom

Other Identifiers

2012-004263-47

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR 200104-011

Identifier Type: -

Identifier Source: org_study_id