Primary: To evaluate the efficacy of once-weekly lonapegsomatropin compared to placebo at 38 weeks in adults with growth hormone deficiency (GHD). Secondary: 1. To evaluate the safety and tolerability of once-weekly lonapegsomatropin in adults with…
ID
Source
Brief title
Condition
- Hypothalamus and pituitary gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy Endpoint:
Change from baseline in trunk percent fat (as assessed by dual-energy x-ray
absorptiometry [DXA]) at Week 38.
Secondary outcome
Secondary Efficacy Endpoints:
• Change from baseline in trunk fat mass at Week 38 (as assessed by DXA)
• Change from baseline in total body lean mass at Week 38 (as assessed by DXA)
Background summary
Although there are various causes of AGHD, current standard treatment aims for
growth hormone replacement by daily injections of recombinant human growth
hormone (rhGH). Recombinant human growth hormone was first approved in the
1980*s and hassince been on the market from
different manufacturers for various indications.Lonapegsomatropin contains the
same active substance (rhGH) as currently marketed daily growth
hormone products but being a long-acting growth hormone product (LAGH) with the
advantage of only requiring one injection per week, hence reducing the number
of injections per week from seven to one.
Study objective
Primary:
To evaluate the efficacy of once-weekly lonapegsomatropin compared to placebo
at 38 weeks in adults with growth hormone deficiency (GHD).
Secondary:
1. To evaluate the safety and tolerability of once-weekly lonapegsomatropin in
adults with GHD
2. To evaluate the pharmacokinetics (PK) of once-weekly lonapegsomatropin in
adults with GHD
3. To evaluate the pharmacodynamics (PD) of once-weekly lonapegsomatropin in
adults with GHD
Study design
This is a randomized, parallel-arm, placebo-controlled, active-controlled trial
and designed to evaluate efficacy of lonapegsomatropin versus placebo. The
daily somatropin product arm is included as a calibration arm to assist
clinical judgement on the trial results.
The trial will consist of:
• Screening Period - up to approx. 4 weeks to establish eligibility (approx. 2
weeks may be added between randomization and the first dose to allow for
logistics and shipments)
• Treatment Period - (38 weeks in total), consisting of: * Dose Titration
Period - 12 weeks of dose titration, scheduled dose titration visits will occur
at Week 4, Week 8, and Week 12
* Dose Maintenance Period - 26 weeks of maintenance treatment, trial visits
will occur at Week 17, Week 28, and Week 38
• Follow-up Period - (4 weeks in total), treatment free period, AEs/SAEs will
be collected via phone 2 weeks after Week 38 (Week 40), an ADA sample will be
taken 4 weeks after Week 38 (Week 42)
Intervention
Randomized subjects will receive the study drug as assigned according to
randomization and dosing group.
Lonapegsomatropin will be provided as a lyophilized powder in single-use glass
vials requiring reconstitution with 1 mL sterile water for injection (sWFI) and
administered by subcutaneous (SC) injection via syringe and needle The placebo
for lonapegsomatropin drug product will contain the same excipients as
lonapegsomatropin drug product but does not contain lonapegsomatropin
itself.Norditropin FlexPro or NordiFlex (somatropin) 5 mg/1.5 mL will be
provided as a commercially approved solution for injection in a pre-filled pen
for SC administration.
Study burden and risks
For decades, hGH has been used all over the world for different types of growth
problems in children, and for controlling metabolism and body composition in
adults, and has been shown to be safe and effective. Lonapegsomatropin has been
investigated in healthy volunteers and patients with GHD (both in children and
in adults) and no major concerns have been observed. It has been shown to be
safe and well tolerated at the dose used for this study. However, like with all
medications, lonapegsomatropin, placebo and Norditropin may exert side effect.
The side effects that have been seen with growth hormone medications are the
following: local injection site reactions, lipoatrophy and scarring, reduced
insulin sensitivity and increased blood sugar levels, development of
anti-growth hormone antibodies, impaired thyroid and adrenal function,
intracranial hypertension, water retention, allergic reaction, pancreatitis,
and headache. Lonapegsomatropin has not been studied in pregnant or nursing
women. Therefore, administration of lonapegsomatropin may involve unknown risks
to an embryo, foetus or nursing infant.
The following assessments will be performed during the study: blood drawing (9
times), MRI and CT assessments (once during the study, if needed), ECG (3-4
times), DXA scan (4 times), fundoscopy (2 times). A total of approximately 50
mL of blood will be taken during Screening Period, a total of approximately 60
mL will be taken during Dose Titration Period and a total of approximately 45
mL will be taken during dose maintenance period. Most visits will take up to
approximately 2 - 3 hours.
Tuborg Boulevard 12
Hellerup DK-2900
DK
Tuborg Boulevard 12
Hellerup DK-2900
DK
Listed location countries
Age
Inclusion criteria
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 at screening (without signs/symptoms of intracranial
hypertension or diabetic retinopathy stage 2 / moderate or above). For subjects
with a diagnosis of diabetes mellitus at screening, this must be documented
with a fundus photograph.
11. Able and willing to provide a written Informed Consent Form (ICF) and
authorization for protected health information (PHI) disclosure in accordance
with Good Clinical Practice (GCP).
Exclusion criteria
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-000929-42-NL |
| ClinicalTrials.gov | NCT04615273 |
| CCMO | NL75768.029.21 |