A clinical study in children with Growth Hormone Deficiency for dose-finding and assessment of safety of TV-1106 (experimental drug).

Phase 1

Conditions: Therapeutic area: Diseases [C] - Hormonal diseases [C19]
Growth hormone deficiency
MedDRA version: 17.0Level: PTClassification code 10056438Term: Growth hormone deficiencySystem Organ Class: 10014698 - Endocrine disorders

Registration Number: EUCTR2013-004468-69-RO

Lead Sponsor: Teva Pharmaceutical Industries, Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: A

Sex: All

Target Recruitment: 60

Inclusion Criteria

a. Pre-pubertal (Tanner 1/1/1) boys = 3 years to = 11 years and pre-pubertal girls = 3 years to = 10 years at time of informed consent signing with isolated idiopathic growth hormone (GH) insufficiency, GH insufficiency as part of multiple pituitary hormone deficiencies, or organic GH insufficiency (e.g., due to pituitary tumor, pituitary or brain surgery, intracranial radiation therapy);
b. Diagnosis confirmed by 2 different GH provocation tests for GH secretion (e.g., insulin tolerance test and arginine test) as described in consensus guidelines (GH Research Society 2000, Gharib et al 2003, Rose 2007). The peak GH concentration must be below 10 ng/mL for inclusion in the study;
c. All patients must have at least one cranial imaging study [magnetic resonance imaging (MRI) or computed tomography (CT)] prior to randomization:
- To exclude intracranial causes of GHD in patients without a history of pituitary tumor [obtained within 6 months prior to informed consent signing (Visit 1-SCR)], or
- Patients with a previously treated pituitary tumor must have no tumor progression for at least the past year [obtained within 3 months prior to informed consent signing (Visit 1), compared with a previous MRI or CT performed at least 12 months earlier].
If not performed within these specified time frames prior to informed consent signing, may be performed as part of the screening procedures.
d. H-SDS = -2.0;
e. HV-SDS <0 (minimum time between 2 standard height measurements should be at least 6 months prior to study entry; one of the measurements can be taken during the screening visit. The data should be determined from medical records and include dates and method of height measurement);
f. IGF-I SDS < -1.0;
g. Body Mass Index (BMI) within the 95th percentile of BMI for CA and sex according to the 2000 Centers for Disease Control (CDC) standards;
h. For girls, normal karyotype;
i. Written Informed Consent of the parent(s) or legal guardian of the patient and a verbal or written assent from the patients, where possible;
j. Parent or legal guardian who is capable and willing to administer the study drug.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

a. Any clinically significant abnormality as determined by the investigator, that is likely to affect growth or ability to grow (e.g., chronic diseases such as renal insufficiency or advanced diseases such as acquired immunodeficiency syndrome [AIDS] or tuberculosis; intracranial, cranio-spinal, or spinal cord irradiation; malnutrition);
b. Contraindications to rhGH treatment;
c. History of or currently active malignancy, including malignant intra-cranial tumors;
d. Children with new diagnosis of pituitary/hypothalamic tumor or of intracranial tumor as confirmed by MRI or CT within 12 months prior to baseline (Visit 2-BL);
e. Bone age, determined by the standard method (Greulich and Pyle, 1959), greater than CA or greater than 9 for girls or greater than 10 for boys within 3 months of screening. If not done within 3 months of screening, may be performed as part of screening procedures;
f. Patients with known diagnosis of diabetes or pre-diabetes (impaired fasting glucose) as defined in the American Diabetes Association position statement (American Diabetes Association, 2013);
g. Chromosomal abnormalities and medical syndromes” (e.g., Noonan syndrome, Turner’s syndrome, Prader-Willi syndrome, Russell-Silver syndrome, short stature homeobox [SHOX], mutations/deletions);
h. Skeletal dysplasias;
i. Children born small for gestational age (SGA, defined as birth weight and/or birth length < -2 standard deviations [SDs] for gestational age);
j. Evidence of closed epiphyses;
k. Growth altering medications such as anabolic steroids or methylphenidate, except for pituitary replacement hormone therapy (thyroxine, hydrocortisone, desmopressin);
l. Children requiring glucocorticoid therapy (e.g., for asthma) in excess of 400 µg/day of inhaled budesonide (or equivalents) inhaled for longer than 1 month during the last calendar year;
m. Poorly controlled or uncontrolled pituitary hormone insufficiencies (i.e., stable therapy less than 6 months for thyroid replacement and 3 months for other hormone replacements);
n. Hypersensitivity to the study medication components;
o. Participation in another investigational agent trial within 30 days prior to screening;
p. Other causes of short stature, such as celiac disease, malabsorption syndromes, untreated hypothyroidism, rickets, psychosocial dwarfism;
q. Any medical condition as judged by the investigator to interfere with patient participation or the objectives of the study;
r. Patients with signs and/or symptoms of increased intracranial pressure at screening.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to determine the safety and tolerability of 3 different weekly doses of TV-1106 and a daily dose of Genotropin® in paediatric patients.;Secondary Objective: The secondary objectives of the study is to evaluate the efficacy of 3 different weekly doses of TV-1106 and a daily dose of Genotropin® as demonstrated by height velocity (HV), height velocity standard deviation score (HV-SDS), and height standard deviation score (H-SDS).;Primary end point(s): The primary efficacy variable and endpoint for this study is<br>HV after 6 months of treatment.;Timepoint(s) of evaluation of this end point: after 6 months of treatment.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary efficacy variables and endpoints for this study are as follows:<br>- HV at 12 months of treatment;<br>- HV-SDS at 6 months and at 12 months of treatment;<br>- Change in H-SDS from baseline to 6 months and 12 months of treatment.;Timepoint(s) of evaluation of this end point: - HV at 12 months of treatment;<br>- HV-SDS at 6 months and at 12 months of treatment;<br>- Change in H-SDS from baseline to 6 months and 12 months of treatment.

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