A clinical study in adults with Growth Hormone Deficiency (GHD) to assess the safety and tolerability of weekly administered TV-1106 (experimental medicinal product) compared to daily administered growth hormone treatment (Genotropin®)

• Register: EUCTR
• Last refreshed on: 28 November 2016
• Main ID: EUCTR2014-002736-13-SI
• Date of registration: 12/05/2015
• Prospective Registration: Yes
• Primary sponsor: Teva Pharmaceutical Industries Ltd.
• Public title: A clinical study in adults with Growth Hormone Deficiency (GHD) to assess the safety and tolerability of weekly administered TV-1106 (experimental medicinal product) compared to daily administered growth hormone treatment (Genotropin®)
• Scientific title: A phase 3, multicenter, randomized, open-label, comparator-controlled study to assess safety and tolerability of weekly TV-1106 compared to daily rhGH (Genotropin®) in adults with growth hormone-deficiency
• Date of first enrolment: 15/10/2015
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002736-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Brazil, Bulgaria, Canada, Chile, Croatia, Czech Republic, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Lithuania, Mexico, Peru, Poland, Romania, Russian Federation, Serbia, Slovakia, Slovenia, Spain, Sweden, Turkey, Ukraine, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Teva Pharma GmbH

• Name: Clinical Trial Information Desk
• Affiliation: Teva Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
Patients may be included in the study if they meet all of the following criteria:
a. provision of written informed consent and agreement to comply with study requirements
b. males and females 18 years of age or over
c. body mass index (BMI) between 19 and 35 kg/m2 inclusive
d. diagnosis of adult GHD for at least 6 months, confirmed by medical record diagnostic testing specified by an accepted guidance (eg, Carroll 1998; Cook 2009; Ho 2007; Molitch 2011) in effect at the time of diagnosis or patients who have hypopituitarism from surgical resection
e. treated with a stable dose of daily rhGH for at least 3 months prior to screening
f. IGF-I SDS level between -0.5 and +1.5 at screening
g. stable, adequate doses of replacement hormones (adrenal, thyroid, estrogen, testosterone, vasopressin) for at least 3 months prior to screening as clinically judged by the investigator to be adequate patients who are not receiving glucocorticoid replacement therapy must have adequate adrenal function confirmed by adrenocorticotropic hormone (ACTH) stimulation test at screening
i. women of child-bearing potential must be willing to use a medically accepted method of contraception for the duration of the study and for 30 days after last study treatment. Acceptable methods of contraception include: double barrier method (condom or diaphragm with spermicide), intrauterine device (IUD), partner’s vasectomy, or steroidal contraceptive (oral, transdermal, implanted, injected). Patients who are gonadotropin deficient, surgically sterile, or at least 1 year post-menopausal are not required to use contraception.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 140
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients will be excluded from participating in this study if they meet 1 or more of the following criteria:
a. patients with acute or chronic conditions or diseases that could confound results of the study or put the patient at undue risk as determined by the investigator
b. patients who have participated in another clinical trial with a new chemical/biological entity within 3 months of screening
c. patients with known active malignancy (excluding surgically removed basal cell carcinoma or carcinoma in situ of cervix)
d. patients with a previously treated pituitary tumor with evidence of tumor progression in the past year (evidence will be established by magnetic resonance imaging [MRI] or computerized tomography [CT] obtained within 3 months of screening or at screening. Patients will be excluded if they show any progression from a prior scan taken at least 12 months prior to the current scan).
e. patients with a new diagnosis of pituitary adenoma or other intracranial tumor within 12 months of screening
f. presence of Prader-Willi syndrome, Turner’s syndrome, untreated adrenal insufficiency, active acromegaly in the past 5 years, or active Cushing’s syndrome in the past year.
g. patients with known allergy or hypersensitivity to rhGH, human serum albumin (HSA), yeast-derived products, or any other component of the formulation
h. patients with previous signs or history of increased intracranial pressure (ICP) with rhGH treatment, or documented ICP or signs of ICP on fundoscopic examination at the time of screening (may be performed by investigator or referred to an ophthalmologist) (patients with previous history of ICP due to treated tumors that have resolved can be included in the study.)
i. patients with severe, clinically significant, persistent or recurring migraines, edema, or history or presence of carpal tunnel syndrome, or other nerve compression symptoms assessed as clinically important by the investigator
j. patients with untreated or poorly controlled stage 2 hypertension (systolic blood pressure [SBP] =150 mmHg and/or diastolic blood pressure [DBP] =90 mmHg).
k. patients with clinically significant abnormalities on the screening laboratory assessments, electrocardiogram (ECG), or physical examination that would confound the interpretation of the study or put the patient at undue risk of participation in the study as determined by the investigator
l. patients with type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus as indicated by a glycated hemoglobin (HbA1c) =8%
m. patients who use anabolic steroids or corticosteroids, except for physiological maintenance doses used as treatment for patients with hormone deficiencies (limited use of low dose glucocorticoid preparations is allowed [eg, topical preparations]; inhaled budesonide will be permitted at a dose not to exceed 400 µg/day for 3 days [total <1200 µg/month] or equivalent.)
n. patients using weight reducing agents or appetite suppressants
o. women who are pregnant or nursing, or planning pregnancy during the study period
p. patients with active or known history of substance abuse that in the investigator’s opinion would affect compliance with the study
q. patients with known tendency to have injection site lipoatrophy


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Growth hormone deficiency
MedDRA version: 18.0 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disorders

Intervention(s)

Product Name: Albutropin
Product Code: TV-1106
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not available yet
Current Sponsor code: TV-1106; Albutropin
Other descriptive name: HUMAN SERUM ALBUMIN (HSA) FUSED TO RECOMBINANT HUMAN GROWTH HORMONE (HGH)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Trade Name: Genotropin
Product Name: Somatropin; Recombinant Human Gowth Hormone
Product Code: Not applicable
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Somatropin
CAS Number: 12629-01-5
Current Sponsor code: Not applicable
Other descriptive name: SOMATROPIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5.3-

Product Name: Albutropin
Product Code: TV-1106
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not available yet
Current Sponsor code: TV-1106; Albutropin
Other descriptive name: HUMAN SERUM ALBUMIN (HSA) FUSED TO RECOMBINANT HUMAN GROWTH HORMONE (HGH)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: The primary objective of this study is to compare the safety and tolerability of weekly TV-1106 with daily Genotropin.

Timepoint(s) of evaluation of this end point: Throughout the study.

Primary end point(s): Safety Variables and Endpoints:
- adverse event reports throughout the study
- clinical laboratory test results
- vital sign measurements
- ECG findings and physical examination findings
- concomitant medication usage throughout the study
- changes in replacement hormones (thyroid-stimulating hormones [TSH], free T4, total T3)
- glucose homeostasis (HbA1c, fasting blood glucose, and insulin)

Tolerability Variables and Endpoints:
- proportion of patients who prematurely discontinue treatment
- proportion of patients who prematurely discontinue treatment due to adverse events
- time to premature treatment discontinuation
- time to premature treatment discontinuation due to adverse events
- proportions of patients with injection site reactions
- proportion of patients with occurrence of lipoatrophy

Secondary Objective: Secondary Objectives: The secondary objective of this study is to assess and compare weekly TV-1106 with daily Genotropin with regard to pharmacodynamic (IGF-I SDS) and exploratory efficacy variables and endpoints.

Exploratory Objectives: To assess and compare quality of life (QOL), injection experience satisfaction, and compliance of weekly TV-1106 with daily Genotropin. To explore potential correlation between genetic polymorphisms and response to TV-1106 (eg, pharmacokinetic, tolerability, and safety features) compared with Genotropin. To explore potential pharmacodynamic markers (as well as those in the secondary objective).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Throughout the study.

Secondary end point(s): Efficacy Variables and Endpoints:
- IGF-I SDS
- QOL: QOL in Adult Growth hormone-deficiency Assessment (QOL-AGHDA) and
EuroQol 5D (EQ5D-5L) questionnaires
- patient satisfaction/experience with injections
- adherence/compliance
- lipid profile

Secondary ID(s)

TV1106-IMM-30022

2014-002736-13-DE

Source(s) of Monetary Support

Teva Pharmaceutical Industries Ltd.