Study of TV-1106 in Growth Hormone-Deficient Adults

Growth Hormone Deficiency Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Efficacy, Safety and Tolerability Study of TV-1106 in Growth Hormone-Deficient Adults Who Are Not Current Users of rhGH Treatment

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02410343
• Other study ID #: TV1106-IMM-30021
• Secondary ID: 2014-003796-32
• Status: Terminated
• Phase: Phase 3
• Start date: April 30, 2015
• Est. completion date: December 31, 2015

Study information

• Verified date: January 2022
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the efficacy of 6 months of treatment with TV-1106 compared with placebo on body fat composition.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: December 31, 2015
• Est. primary completion date: December 31, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion:

• males and females 18 years of age or over

• diagnosis of adult growth hormone deficiency (GHD) for at least 6 months, or patients who have hypopituitarism from surgical resection

• no history of exposure to any rhGH within the past 12 months prior to screening

• stable, adequate doses of replacement hormones (adrenal, thyroid, estrogen, testosterone, vasopressin) for at least 3 months prior to screening

• Other criteria apply, please contact the investigator for more information

Exclusion:

• 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

• Presence of contraindications to rhGH treatment

• patients who have participated in another clinical trial with a new chemical/biological entity within 3 months of screening

• patients with known active malignancy (excluding surgically removed basal cell carcinoma or carcinoma in situ of cervix)

• patients with a previously treated pituitary tumor with evidence of tumor progression in the past year patients with a new diagnosis of pituitary adenoma or other intracranial tumor within 12 months of screening

• 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 1 year

• patients with type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus as indicated by a glycated hemoglobin (HBA1c) of =8%

• patients using weight reducing agents or appetite suppressants

• women who are pregnant or nursing, or planning pregnancy during the study period

• Other criteria apply, please contact the investigator for more information

Related Conditions & MeSH terms

• Growth Hormone Deficiency

Intervention

Drug:
• TV-1106
A starting dose of 5.0 mg was expected to be appropriate for most patients because the daily recommended starting dose of recombinant human growth hormone (rhGH) treatments (e.g. somatropin) is 0.2 mg/day, and the conversion factor was 28. Dosage could be titrated by an unblinded central reader on weeks 4, 8, 12 and 16 until the participant's insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) was within the range of -0.5 to +1.5.
• Placebo
Placebo treatment was administered in a blinded fashion and titrated on weeks 4, 8, 12 and 16 to mimic the active treatment.

Locations

Country	Name	City	State
Austria	Teva Investigational Site 33030	Linz
Czechia	Teva Investigational Site 54112	Moravskoslezsky
Greece	Teva Investigational Site 63054	Athens
Greece	Teva Investigational Site 63053	Chaidari
Hungary	Teva Investigational Site 51197	Budapest
Hungary	Teva Investigational Site 51195	Pecs
Italy	Teva Investigational Site 30112	Brescia
Russian Federation	Teva Investigational Site 50303	Saint-Petersburg
United States	Teva Investigational Site 13110	Arlington	Texas
United States	Teva Investigational Site 13102	Artesia	California
United States	Teva Investigational Site 13096	Asheville	North Carolina
United States	Teva Investigational Site 13109	Brooklyn	New York
United States	Teva Investigational Site 13104	Chicago	Illinois
United States	Teva Investigational Site 13125	Dallas	Texas
United States	Teva Investigational Site 13101	Detroit	Michigan
United States	Teva Investigational Site 13124	Evansville	Indiana
United States	Teva Investigational Site 13126	Fountain Valley	California
United States	Teva Investigational Site 13127	Fountain Valley	California
United States	Teva Investigational Site 13112	Henderson	Nevada
United States	Teva Investigational Site 13097	Houston	Texas
United States	Teva Investigational Site 13107	Houston	Texas
United States	Teva Investigational Site 13120	Houston	Texas
United States	Teva Investigational Site 13113	Las Vegas	Nevada
United States	Teva Investigational Site 13103	Miami	Florida
United States	Teva Investigational Site 13118	Miami	Florida
United States	Teva Investigational Site 13123	Miami	Florida
United States	Teva Investigational Site 13492	Miami	Florida
United States	Teva Investigational Site 13114	Miami Lakes	Florida
United States	Teva Investigational Site 13106	New York	New York
United States	Teva Investigational Site 13494	New York	New York
United States	Teva Investigational Site 13100	Pembroke Pines	Florida
United States	Teva Investigational Site 13108	Pittsburgh	Pennsylvania
United States	Teva Investigational Site 13121	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Czechia,  Greece,  Hungary,  Italy,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period	The primary efficacy measure for the study was body fat mass (kg) measured by DXA imaging. The primary outcome as defined in the protocol was the change from baseline to week 24 in body fat mass. Due to the early termination of the study, observed values including endpoint values are reported. Endpoint is the last observed value.	Baseline (Day 1, pre-dose), Week 24, Endpoint in Core period
Secondary	Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period	Trunk fat (kg) was assessed based on DXA results. Trunk fat was defined as fat mass - (total arm fat + total leg fat + total head fat). The outcome as defined in the protocol was the within-patient change from baseline to week 24 in trunk fat. Due to the early termination of the study, observed values including endpoint values are reported. Endpoint is the last observed value.	Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period
Secondary	Insulin-Like Growth Factor 1 Standard Deviation Score (IGF-I SDS) at Baseline, Week 24 and Endpoint in Core Period	IGF-I SDS, as reported by the central laboratory, was a key secondary variable. The week 24 value is a trough value as it was taken 7 days after the last TV-1106 or placebo injection. The outcome as defined in the protocol was the within-patient change from baseline to week 24. Due to the early termination of the study, observed values including endpoint values are reported. Endpoint is the last observed value and is of variable length of time since last TV-1106 or placebo injection.	Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period
Secondary	Scored Analysis of Quality of Life Assessment of GH Deficiency in Adults (QoL-AGHDA) at Baseline, Week 24 and Endpoint in Core Period	The AGHDA instrument is comprised of 25 questions, with yes or no answers. To each of the 25 questions comprising QOL AGHDA, a score of 1 was assigned if the answer was affirmative and 0 if the answer was negative. Data reported is the total score across the 25 questions for a total range of 0-25 with higher scores representing a poorer quality of life. The outcome as defined in the protocol was the within-patient change from baseline to week 24. Due to the early termination of the study, observed values including endpoint values are reported. Endpoint is the last observed value.	Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period
Secondary	Participants With Adverse Events During the Core Period	An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents usual activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.	Day 1 up to 24 Weeks
Secondary	Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results	Parameters with potentially clinically significant abnormal test results include - Serum chemistry: blood urea nitrogen, creatinine and bilirubin - Hematology: leukocytes, hemoglobin, hematocrit, platelets and neutrophils - Urinalysis: none Significance criteria are listed below with the test.	Day 1 up to 24 Weeks
Secondary	Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings	Shifts represented as baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicates an abnormal but not clinically significant finding. Abnormal CS indicates an abnormal and clinically significant finding.	Day 1 up to Week 24
Secondary	Thyroid Stimulating Hormone (TSH) at Baseline and Endpoint	One measure of changes in replacement hormones.	Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Secondary	Free Thyroxin (Free T4) at Baseline and Endpoint	One measure of changes in replacement hormones.	Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Secondary	Triiodothyronine (Total T3) at Baseline and Endpoint	One measure of changes in replacement hormones.	Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Secondary	Glycated Hemoglobin (HbA1c) at Baseline and Endpoint	One measure of glucose homeostasis.	Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Secondary	Fasting Blood Glucose at Baseline and Endpoint	One measure of glucose homeostasis.	Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Secondary	Insulin at Baseline and Endpoint	One measure of glucose homeostasis.	Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Secondary	Local Tolerability Assessed by Injection Site Reactions	Participants reporting at least one injection site reaction.	Daay 1 up to Week 24
Secondary	Pharmacokinetic Serum Concentration of TV1106 by Nominal Sampling Timepoints	Weeks 4 and 8 serum samples obtained 2 days after TV1106 administration. Weeks 12 and 24 serum samples obtained 7 days after TV1106 administration. Week 16 serum samples obtained 1 day after TV1106 administration.	Baseline (Day 1, pre-dose), Weeks 4, 8, 12, 16, 24