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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Merck KGaA
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01806298
First received: March 5, 2013
Last updated: July 18, 2014
Last verified: July 2014
  Purpose

This is an open-label, single-arm, multicenter, Phase 4 study to explore the immunogenicity of the liquid formulation of Saizen® in subjects with Growth Hormone Deficiency (GHD) of adult onset, who are growth hormone (GH) treatment-naïve or who had prior GH treatment for adult growth hormone deficiency (AGHD) which was stopped at least 3 months prior to Screening.


Condition Intervention Phase
Growth Hormone Deficiency
Drug: Saizen® solution for injection (referred as Saizen®)
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Single-arm, Phase IV, Multicenter Trial to Explore the Immunogenicity of the Liquid Formulation of Saizen® in Subjects With Growth Hormone Deficiency (GHD) of Adult Onset

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Percentage of subjects developing Binding Antibodies (BAbs) to Saizen® [ Time Frame: Baseline up to Week 39 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of subjects with BAbs who become positive for Neutralizing Antibody (NAbs) [ Time Frame: Baseline up to 2 weeks after last dose of study treatment ] [ Designated as safety issue: Yes ]
  • Insulin-like growth Factor-I (IGF-I) levels [ Time Frame: Baseline, and Week 2, 8, 16, 29, 39 and 41 ] [ Designated as safety issue: Yes ]
  • Insulin-like growth factor binding Protein-3 (IGFBP-3) levels [ Time Frame: Baseline, and Week 2, 8, 16, 29, 39 and 41 ] [ Designated as safety issue: Yes ]
  • Insulin-like Growth Factor-I Standard Deviation Score (IGF-I SDS) levels [ Time Frame: Baseline, and Week 2, 8, 16, 29, 39 and 41 ] [ Designated as safety issue: Yes ]
  • Treatment adherence rate for each subject as documented using EasypodTM connect [ Time Frame: Week 2, 8, 16, 29 and 39 ] [ Designated as safety issue: No ]
  • Number of subjects with treatment-emergent adverse events [ Time Frame: Week 2, 8, 16, 29 and 39 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 77
Study Start Date: June 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Saizen® Drug: Saizen® solution for injection (referred as Saizen®)
Saizen® solution for injection will be administered subcutaneously daily for 39 weeks according to the local product label instructions on locally approved product labeling.
Other Names:
  • Somatropin
  • Recombinant human growth hormone (r-hGH)

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects, 18-65 years of age, inclusive, at the time of signature of informed consent
  • Documented adult-onset adult growth hormone deficiency (AO-AGHD), either by a stimulation test as described in the GH Research Society's 2007 guidelines for the diagnosis and treatment of adult GHD, 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/m2) indicates a peak GH less than 11 ng/mL microgram per liter [µg/L]).
      • BMI 25-30 kg/m2 indicates a peak GH less than 8 ng/mL (µg/L).
      • BMI greater than 30 kg/m2 indicates a peak GH less than 4 ng/mL (µg/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 3 months 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/m2)
  • 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
  • History or presence of any malignant tumor
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01806298

Contacts
Contact: Merck KGaA Communication Center +49 6151 72 5200 service@merckgroup.com

Locations
Germany
Please contact the Merck KgaA Communications Service located in Recruiting
Darmstadt, Germany
Contact    +49-6151-72-5200    service@merckgroup.com   
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Medical Director Merck KGaA
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01806298     History of Changes
Other Study ID Numbers: EMR 200104-011, 2012-004263-47
Study First Received: March 5, 2013
Last Updated: July 18, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Czech Republic: Ethics Committee
Czech Republic: State Institute for Drug Control
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Institute for Health Research

Keywords provided by Merck KGaA:
Growth hormone deficiency
Saizen®
Recombinant human growth hormone (r-hGH)
Somatropin

Additional relevant MeSH terms:
Dwarfism, Pituitary
Endocrine System Diseases
Bone Diseases
Bone Diseases, Developmental
Bone Diseases, Endocrine
Brain Diseases
Central Nervous System Diseases
Dwarfism
Hypopituitarism
Hypothalamic Diseases
Musculoskeletal Diseases
Nervous System Diseases
Pituitary Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014