foresiGHt: A multicenter, randomized, parallel-arm, placebo- controlled (double- blind) and active-controlled (open-label) trial to compare the efficacy and safety of once-weekly lonapegsomatropin with placebo and a daily somatropin product in adults with growth hormone deficiency
- Conditions
- Lack of growth hormone in the bodyAdult Growth hormone deficiency10021112
- Registration Number
- NL-OMON52023
- Lead Sponsor
- Ascendis Pharma Endocrinology Division A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 32
1. Age between 23 and 75 years, inclusive, at screening.
2. AGHD Diagnosis Criteria
For adult-onset AGHD: documented history of structural hypothalamic-pituitary
disease, hypothalamic-pituitary surgery, cranial irradiation, 1-4 non-GH
pituitary hormone deficiencies, a proven genetic cause of GHD, or traumatic
brain injury (TBI).
Subjects with childhood-onset GHD must have had GH axis re assessed at final
height.
In subjects with TBI as a cause of GHD, GHD must be confirmed by GH stimulation
testing performed at least 12 months after the injury.
For all subjects, documentation of test results must be available before
randomization. Stimulation test protocols and results are subject to review and
approval by the Medical Monitor.
A. For all countries except Japan: Subjects must satisfy at least one of the
following criteria:
a. Insulin tolerance test: peak GH <=5 ng/mL
b. Glucagon stimulation test according to body mass index (BMI)
i. BMI <=30 kg/m2: peak GH <=3 ng/mL
ii. BMI >30 kg/m2: peak GH <=1 ng/mL
c. Three or four pituitary axis deficiencies (ie, adrenal, thyroid, gonadal,
and/or vasopressin; not including GH) with IGF-1 SDS <= -2.0 at screening as
measured by central laboratory,
d. Macimorelin test: peak GH <=2.8 ng/mL
e. Growth hormone-releasing hormone (GHRH) + arginine test according to BMI:
i. BMI <25 kg/m2, peak GH <11 ng/mL
ii. BMI >=25-<=30 kg/m2, peak GH <8 ng/mL
iii. BMI >30 kg/m2, peak GH <4 ng/mL
B. For Japan only: Subjects with adult-onset AGHD and deficiency of one or more
other pituitary hormones need to satisfy at least one of the following
criteria, while subjects with isolated GHD and no evidence of intracranial
structure disorder (structural hypothalamic-pituitary disease) or with
adult-onset AGHD without deficiency of other pituitary hormones need to satisfy
at least 2 of the following criteria:
a. Insulin tolerance test: peak GH <=1.8 ng/mL
b. Glucagon test: peak GH <=1.8 ng/mL
c. Growth Hormone-Releasing Peptide-2 (GHRP-2) tolerance test: peak GH <=9 ng/mL
3. IGF-1 SDS <= -1.0 at screening as measured by central laboratory.
4. hGH treatment-naïve or no exposure to hGH therapy or GH secretagogue for at
least 12 months prior to screening.
5. For subjects on hormone replacement therapies for any hormone deficiencies
other than GH (eg, adrenal, thyroid, estrogen, testosterone) must be on
adequate and stable doses for >=6 weeks prior to and throughout screening.
6. For subjects not on glucocorticoid replacement therapy, documentation of
adequate adrenal function at screening defined as: morning (6:00-10:00AM) serum
cortisol >15.0 ng/mL (measured at central laboratory) and/or
Adrenocorticotrophic Hormone (ACTH) stimulation test or ITT with serum cortisol
>18.0 ng/mL at or within 26 weeks prior to screening.
7. For males not on testosterone replacement therapy: morning (6:00 10:00AM)
total testosterone within normal limits for age as measured by the central
laboratory at screening.
8. On a stable diet and exercise regime at screening with no intention to
modify diet or exercise pattern during the trial, ie, no weight reduction
program intended during the trial or within the last 90 days prior to or
through screening.
9. No plans to undergo bariatric surgery during the trial.
10. Normal fundoscopy
1. Known Prader-Willi Syndrome and/or other genetic diseases that may have an
impact on an endpoint; individual cases to be discussed by the Investigator
with the Medical Monitor.
2. Diabetes mellitus at screening if any of the following criteria are met:
a. Poorly controlled diabetes, defined as HbA1c >7.5% at screening according
to central laboratory
b. Diabetes mellitus (defined as HbA1c >=6.5% and/or fasting plasma glucose >=126
mg/dL and/or plasma glucose >=200 mg/dL two hours after oral glucose tolerance
test) diagnosed <26 weeks prior to screening
c. Change in diabetes regimen (includes dose adjustment) within <90 days
prior and throughout screening
d. Use of any diabetes drugs other than metformin and/or DPP 4 inhibitors for a
cumulative duration of greater than 4 weeks within 12 months prior to screening
e. Diabetes-related complications at screening (ie, nephropathy as judged by
the investigator, neuropathy requiring pharmacological treatment, retinopathy
stage 2 / moderate and above within 90 days prior to screening or during
screening)
3. Active malignant disease or history of malignancy. Exceptions to this
exclusion criterion:
a. Resection of in situ carcinoma of the cervix uteri
b. Complete eradication of squamous cell or basal cell carcinoma of the skin
c. Subjects with GHD attributed to treatment of intracranial malignant tumors
or leukemia, provided that a recurrence-free survival period of at least 5
years prior to screening is documented in the subject*s file based on a
Magnetic Resonance Imaging (MRI) result
4. Evidence of growth of pituitary adenoma or other benign intracranial tumor
within the last 12 months before screening.
5. Subjects with acromegaly without remission / with documented remission less
than 24 months prior to screening.
6. Subjects with Cushing*s disease without remission / with documented
remission less than 24 months prior to screening.
7. Subjects with prior cranial irradiation or hypothalamic-pituitary surgery:
the procedure took place less than 12 months prior to screening.
8. Any disease or condition that, in the judgement of the investigator, may
make the subject unlikely to comply with the requirements of the trial or any
condition that presents undue risk from the investigational product or
procedures.
9. Participation in another interventional clinical trial involving an
investigational compound within 26 weeks prior to screening or in parallel to
this trial.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy Endpoint:<br /><br>Change from baseline in trunk percent fat (as assessed by dual-energy x-ray<br /><br>absorptiometry [DXA]) at Week 38. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Efficacy Endpoints:<br /><br>• Change from baseline in trunk fat mass at Week 38 (as assessed by DXA)<br /><br>• Change from baseline in total body lean mass at Week 38 (as assessed by DXA) </p><br>