Study of TV-1106 in Growth Hormone-Deficient Adults

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

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.

Study Overview

• Status: Terminated
• Conditions: Growth Hormone Deficiency
• Intervention / Treatment: Drug: Placebo; Drug: TV-1106

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, A-4020
    • Teva Investigational Site 33030
• Czechia
  • Moravskoslezsky, Czechia, 708 00
    • Teva Investigational Site 54112
• Greece
  • Athens, Greece, 11527
    • Teva Investigational Site 63054
  • Chaidari, Greece, 12462
    • Teva Investigational Site 63053
• Hungary
  • Budapest, Hungary, 1088
    • Teva Investigational Site 51197
  • Pecs, Hungary, 7624
    • Teva Investigational Site 51195
• Italy
  • Brescia, Italy, 25018
    • Teva Investigational Site 30112
• Russian Federation
  • Saint-Petersburg, Russian Federation
    • Teva Investigational Site 50303
• United States
  • California
    • Artesia, California, United States, 90701
      • Teva Investigational Site 13102
    • Fountain Valley, California, United States, 33155-6541
      • Teva Investigational Site 13127
    • Fountain Valley, California, United States, 92708
      • Teva Investigational Site 13126
  • Florida
    • Miami, Florida, United States, 33126
      • Teva Investigational Site 13103
    • Miami, Florida, United States, 33130
      • Teva Investigational Site 13118
    • Miami, Florida, United States, 33145
      • Teva Investigational Site 13123
    • Miami, Florida, United States, 33155-6541
      • Teva Investigational Site 13492
    • Miami Lakes, Florida, United States, 33016
      • Teva Investigational Site 13114
    • Pembroke Pines, Florida, United States, 33024
      • Teva Investigational Site 13100
    • West Palm Beach, Florida, United States, 33401
      • Teva Investigational Site 13121
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Teva Investigational Site 13104
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Teva Investigational Site 13124
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Teva Investigational Site 13101
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Teva Investigational Site 13112
    • Las Vegas, Nevada, United States, 89148
      • Teva Investigational Site 13113
  • New York
    • Brooklyn, New York, United States, 11235
      • Teva Investigational Site 13109
    • New York, New York, United States, 10016
      • Teva Investigational Site 13494
    • New York, New York, United States, 10032
      • Teva Investigational Site 13106
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Teva Investigational Site 13096
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Teva Investigational Site 13108
  • Texas
    • Arlington, Texas, United States, 76014
      • Teva Investigational Site 13110
    • Dallas, Texas, United States, 75218
      • Teva Investigational Site 13125
    • Houston, Texas, United States, 77079
      • Teva Investigational Site 13097
    • Houston, Texas, United States, 77084
      • Teva Investigational Site 13107
    • Houston, Texas, United States, 77090
      • Teva Investigational Site 13120

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo was injected subcutaneously once weekly on the same day and time for 24 weeks. To maintain the blind, placebo could be titrated by an unblinded central reader on weeks 4, 8, 12 and 16 to match the effect of dose titration.	Drug: Placebo; Placebo treatment was administered in a blinded fashion and titrated on weeks 4, 8, 12 and 16 to mimic the active treatment.; Other Names: Matching placebo
Experimental: TV-1106; TV-1106 was injected subcutaneously once weekly on the same day and time for 24 weeks. A common starting dose was 5.0 mg. Doses 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.	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.; Other Names: long-acting growth hormone, albutropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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)
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)
Triiodothyronine (Total T3) at Baseline and Endpoint	One measure of changes in replacement hormones.	Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Glycated Hemoglobin (HbA1c) at Baseline and Endpoint	One measure of glucose homeostasis.	Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Fasting Blood Glucose at Baseline and Endpoint	One measure of glucose homeostasis.	Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Insulin at Baseline and Endpoint	One measure of glucose homeostasis.	Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Local Tolerability Assessed by Injection Site Reactions	Participants reporting at least one injection site reaction.	Daay 1 up to Week 24
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

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2015
• Primary Completion (Actual): December 31, 2015
• Study Completion (Actual): December 31, 2015

Study Registration Dates

• First Submitted: March 30, 2015
• First Submitted That Met QC Criteria: April 1, 2015
• First Posted (Estimate): April 7, 2015

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: long acting growth hormone
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: TV1106-IMM-30021; 2014-003796-32 (EudraCT Number)