Adult Growth Hormone Deficiency
Conditions
Brief summary
This will be a randomized, double-blind, placebo-controlled, parallel-group, multicenter study in adult subjects with GHD to assess the safety and efficacy of a long-acting, once weekly injection of modified hGH (MOD-4023).
Interventions
DRUGMOD-4023
Individualized once weekly dose of MOD-4023
OTHERPlacebo
Once weekly administration of placebo
Sponsors
OPKO Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
23 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Men and women between the age of 23 to 70 years old at screening, inclusive * GHD subjects as defined in the Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II (2007). * No r-hGH replacement therapy or use of GH secretagogues for at least 9 months with any registered or investigational r-hGH or GH secretagogue product. * The IGF-I level at screening ≤-1 SDS of the age and sex normal ranges according to the central laboratory measurements * Subjects who are on a stable diet and exercise regime and do not have plans to modify their diet or exercise for at least 12 months * Subject had a DXA screening and the results are interpretable according to the study plan.
Exclusion criteria
* Women who are pregnant or breast-feeding (at least 6 months delay from childbirth or lactation) * Evidence of growth benign intracranial tumor within the last 12 months (determined by comparing a previous MRI to a new one obtained no more than 6 months prior to study entry to clarify dynamics of growth). * History of any cancer. Exceptions to this exclusion criterion include resected in situ carcinoma of the cervix and squamous cell or basal cell carcinoma of the skin with complete local excision. Patients with GHD attributed to treatment of intracranial malignant lesions in childhood or adulthood (or, tumors) or leukemia may also be enrolled into the study provided that a recurrence-free survival period of at least 5 years is well documented in the study record. * Signs of intracranial hypertension at screening * Heart insufficiency, NYHA class \> 2 (Appendix B) * History of overt diabetes mellitus (including currently treated, well-controlled DM) defined according to the American Diabetes Association (ADA) Criteriaa. A history of gestational diabetes, resolved after childbirth, is not exclusionary. * History of Acromegaly
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Trunk Fat Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26 | Baseline to 26 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in Lean Body Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26 | Baseline to 26 weeks |
| Change in Trunk Fat Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to 52 Weeks | Baseline to 52 weeks |
| Change in Total Fat Mass, Expressed in Kilograms, Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26 | Baseline to 26 weeks |
| Trunk Fat Mass as Percentage of Total Fat Mass From Baseline to Week 26 | Baseline to 26 weeks |
| Change in Biochemical Marker IGF-1 | Baseline to 26 weeks |
| Change in Trunk Fat Mass, Expressed as % Change From Baseline, Measured With Dual-energy X-ray Absorptiometry, From Baseline to 26 and 52 Weeks | 26 weeks to 52 weeks |
Countries
Israel
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MOD-4023 MOD-4023: Individualized once weekly dose of MOD-4023 | 133 |
| Placebo Placebo: Once weekly administration of placebo | 65 |
| Total | 198 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 26 - 52 Weeks | Adverse Event | 0 | 1 |
| 26 - 52 Weeks | Lost to Follow-up | 1 | 0 |
| 26 - 52 Weeks | Withdrawal by Subject | 2 | 1 |
| 52 Weeks to End of Study | Adverse Event | 2 | 1 |
| 52 Weeks to End of Study | Death | 0 | 1 |
| 52 Weeks to End of Study | Diabetes not controlled | 0 | 1 |
| 52 Weeks to End of Study | Lack of contact | 1 | 0 |
| 52 Weeks to End of Study | Lost to Follow-up | 1 | 0 |
| 52 Weeks to End of Study | Occurrence of malignancy | 1 | 0 |
| 52 Weeks to End of Study | Personal reasons | 2 | 1 |
| 52 Weeks to End of Study | Progressive disease | 1 | 1 |
| 52 Weeks to End of Study | Protocol Violation | 1 | 0 |
| 52 Weeks to End of Study | Sponsor's decision | 1 | 1 |
| 52 Weeks to End of Study | Study termination by sponsor | 0 | 1 |
| 52 Weeks to End of Study | Withdrawal by Subject | 18 | 8 |
| From Baseline to Week 26 | Adverse Event | 3 | 2 |
| From Baseline to Week 26 | Site and study closed by PI | 0 | 1 |
| From Baseline to Week 26 | Withdrawal by Subject | 3 | 6 |
Baseline characteristics
| Characteristic | MOD-4023 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.9 Year STANDARD_DEVIATION 12.6 | 43.1 Year STANDARD_DEVIATION 12.9 | 43.9 Year STANDARD_DEVIATION 12.6 |
| BMI | 27.0 Kilogram/meter^2 STANDARD_DEVIATION 3.2 | 27.7 Kilogram/meter^2 STANDARD_DEVIATION 3.5 | 27.0 Kilogram/meter^2 STANDARD_DEVIATION 3.2 |
| Race/Ethnicity, Customized Asian | 15 Participants | 8 Participants | 23 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Reported | 5 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 110 Participants | 53 Participants | 163 Participants |
| Region of Enrollment East Asia | 14 participants | 7 participants | 21 participants |
| Region of Enrollment Europe | 88 participants | 43 participants | 131 participants |
| Region of Enrollment United States | 31 participants | 15 participants | 46 participants |
| Sex: Female, Male Female | 57 Participants | 25 Participants | 82 Participants |
| Sex: Female, Male Male | 76 Participants | 40 Participants | 116 Participants |
| Weight | 75.2 Kilogram STANDARD_DEVIATION 15 | 77.8 Kilogram STANDARD_DEVIATION 17.9 | 75.2 Kilogram STANDARD_DEVIATION 15 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 133 | 0 / 65 | 0 / 133 | 0 / 65 | 0 / 111 | 1 / 50 |
| other Total, other adverse events | 36 / 133 | 27 / 65 | 28 / 133 | 16 / 65 | 46 / 111 | 30 / 50 |
| serious Total, serious adverse events | 4 / 133 | 5 / 65 | 5 / 133 | 3 / 65 | 10 / 111 | 8 / 50 |
Outcome results
Primary
Change in Trunk Fat Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26
Time frame: Baseline to 26 weeks
Population: 198 of the 202 randomized subjects received treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOD-4023 | Change in Trunk Fat Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26 | -0.3 kg | Standard Deviation 1.2 |
| Placebo | Change in Trunk Fat Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26 | 0.1 kg | Standard Deviation 1.6 |
Secondary
Change in Biochemical Marker IGF-1
Time frame: Baseline to 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOD-4023 | Change in Biochemical Marker IGF-1 | 134.1 ug/L | Standard Deviation 42.4 |
| Placebo | Change in Biochemical Marker IGF-1 | 54.5 ug/L | Standard Deviation 29.2 |
Secondary
Change in Lean Body Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26
Time frame: Baseline to 26 weeks
Population: 3 subjects discontinued MOD-4023 due to consent withdrawn or lost to follow-up. 2 subjects discontinued placebo due to consent withdrawn or adverse event.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOD-4023 | Change in Lean Body Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26 | 1.3 kg | Standard Deviation 2.4 |
| Placebo | Change in Lean Body Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26 | 0.0 kg | Standard Deviation 1.6 |
Secondary
Change in Total Fat Mass, Expressed in Kilograms, Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26
Time frame: Baseline to 26 weeks
Population: 3 subjects discontinued MOD-4023 due to consent withdrawn or lost to follow-up. 2 subjects discontinued placebo due to consent withdrawn or adverse event.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOD-4023 | Change in Total Fat Mass, Expressed in Kilograms, Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26 | -0.18 kg | Standard Deviation 2.21 |
| Placebo | Change in Total Fat Mass, Expressed in Kilograms, Measured With Dual-energy X-ray Absorptiometry, From Baseline to Week 26 | 0.00 kg | Standard Deviation 2.64 |
Secondary
Change in Trunk Fat Mass, Expressed as % Change From Baseline, Measured With Dual-energy X-ray Absorptiometry, From Baseline to 26 and 52 Weeks
Time frame: 26 weeks to 52 weeks
Population: 3 subjects discontinued MOD-4023 due to consent withdrawn or lost to follow-up. 2 subjects discontinued placebo due to consent withdrawn or adverse event.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOD-4023 | Change in Trunk Fat Mass, Expressed as % Change From Baseline, Measured With Dual-energy X-ray Absorptiometry, From Baseline to 26 and 52 Weeks | % Change from baseline in week 26 | -2.4 percentage of change from baseline | Standard Deviation 8.5 |
| MOD-4023 | Change in Trunk Fat Mass, Expressed as % Change From Baseline, Measured With Dual-energy X-ray Absorptiometry, From Baseline to 26 and 52 Weeks | % Change from baseline in week 52 | -1.6 percentage of change from baseline | Standard Deviation 3.1 |
| Placebo | Change in Trunk Fat Mass, Expressed as % Change From Baseline, Measured With Dual-energy X-ray Absorptiometry, From Baseline to 26 and 52 Weeks | % Change from baseline in week 26 | 0.8 percentage of change from baseline | Standard Deviation 10 |
| Placebo | Change in Trunk Fat Mass, Expressed as % Change From Baseline, Measured With Dual-energy X-ray Absorptiometry, From Baseline to 26 and 52 Weeks | % Change from baseline in week 52 | -1.2 percentage of change from baseline | Standard Deviation 2.8 |
Secondary
Change in Trunk Fat Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to 52 Weeks
Time frame: Baseline to 52 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOD-4023 | Change in Trunk Fat Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to 52 Weeks | -0.2 kg | Standard Deviation 1.6 |
| Placebo | Change in Trunk Fat Mass, Expressed in Kilograms Measured With Dual-energy X-ray Absorptiometry, From Baseline to 52 Weeks | -0.3 kg | Standard Deviation 2.1 |
Secondary
Trunk Fat Mass as Percentage of Total Fat Mass From Baseline to Week 26
Time frame: Baseline to 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOD-4023 | Trunk Fat Mass as Percentage of Total Fat Mass From Baseline to Week 26 | -1.8 percentage of change from baseline | Standard Deviation 3 |
| Placebo | Trunk Fat Mass as Percentage of Total Fat Mass From Baseline to Week 26 | 0.6 percentage of change from baseline | Standard Deviation 2.7 |