A Multicenter, Open-Label, Extension Trial to Investigate Long Term Efficacy and Safety of Lonapegsomatropin in Adults with Growth Hormone Deficiency

JRCT ID: jRCT2041210156

Registered date:05/03/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Adult Growth Hormone Deficiency (AGHD)
• Date of first enrollment: 08/03/2022
• Target sample size: 24
• Countries of recruitment: USA,Japan,Armenia,Japan,Canada,Japan,France,Japan,Georgia,Japan,Germany,Japan,Greece,Japan,Israel,Japan,Italy,Japan,Republic of Korea,Japan,Malaysia,Japan,Poland,Japan,Romania,Japan,Serbia,Japan,Slovakia,Japan,Spain,Japan,Turkey,Japan,Ukraine,Japan,United Kingdom,Japan,Australia,Japan
• Study type: Interventional

Intervention(s)

Lonapegsomatropin will be provided as a lyophilized powder in single-use glass vials requiring reconstitution with 1 mL sWFI and administered by SC injection via syringe and needle or via the auto-injector.
Due to the different hGH dose requirements, depending on participants' age and receipt of concomitant oral estrogen, this trial will have three dosing groups.
Participants will be initiated on a low dose, and the dose will slowly be increased to avoid adverse reactions as much as possible (Dose Titration Period) until the target maintenance dose is reached (Dose Maintenance Period).
Dose Group 1 [Oral estrogen intake (any age) or below 30 years old]
Week 1-4: 2.1 mg hGH/week, Week 5-8: 3.6 mg hGH/week, Week 9-12: 5.2 mg hGH/week, Week 13-52 (Dose Maintenance Period): 6.3 mg hGH/week
Dose Group 2 [30 to 60 years old (both included) and no oral estrogen intake]
Week 1-4: 1.4 mg hGH/week, Week 5-8: 2.1 mg hGH/week, Week 9-12: 3.0 mg hGH/week, Week 13-52 (Dose Maintenance Period): 4.3 mg hGH/week
Dose Group 3 (Over 60 years old and no oral estrogen intake)
Week 1-4: 0.7 mg hGH/week, Week 5-8: 1.4 mg hGH/week, Week 9-12: 2.1 mg hGH/week, Week 13-52 (Dose Maintenance Period): 3.0 mg hGH/week

Outcome(s)

Primary Outcome

Safety endpoints:
- AEs
- Laboratory values
- Vital signs
- Immunogenicity
- 12-lead ECGs
- Fundoscopy

Key inclusion & exclusion criteria

• Age minimum: >= 23age old
• Age maximum: <= 81age old
• Gender: Both

Include criteria

A.For Subjects who completed TCH-306
1. Signing of the trial specific informed consent
2. Completion of the treatment period and Visit 7 assessments of trial TCH-306, including collection and upload of Visit 7 DXA scan
3. Fundoscopy at Visit 7 in trial TCH-306 without signs/symptoms of intracranial hypertension or diabetic retinopathy stage 2 / moderate or above
B.For Subjects who are switching from commercially available daily somatropin treatment (Japan only)
1.Signing of Informed Consent Form and authorization for protected health information (PHI) disclosure in accordance with Good Clinical Practice (GCP)
2.Age between 23 and 80 years, inclusive, at screening
3.Diagnosis of adult GHD >=6 months prior to screening
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 enrollment. Growth hormone stimulation test results are subject to review by the Medical Monitor.
Subjects with GHD and deficiency of at least one non-GH pituitary hormone need to satisfy one of the following GH stimulation tests. Subjects with GHD and without additional non-GH pituitary hormone deficiencies with or without evidence of intracranial structure disorder need to satisfy at least 2 of the following stimulation tests:
a.Insulin tolerance test: peak GH <=1.8 ng/mL
b.Glucagon test: peak GH <=1.8 ng/mL
c.GHRP-2 tolerance test: peak GH <=9 ng/mL
4.IGF-1 SDS >= -2.0 and <= +2.0 at screening as measured by central laboratory
5.Treatment with commercially available daily somatropin consecutively for >=6 months prior to screening. It is acceptable to have been discontinued within 30 days prior to screening.
6.For subjects on hormone replacement therapies for any hormone deficiencies other than GH (e.g., adrenal, thyroid, estrogen, testosterone), must be on adequate and stable doses for >=6 weeks prior to and throughout screening
7.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 mcg/dL (measured at central laboratory) and/or Adrenocorticotrophic Hormone (ACTH) stimulation test or ITT with serum cortisol >18.0 mcg/dL at or within 90 days prior to screening. Stimulation test protocols and results are subject to review and approval by the Medical Monitor
8.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
9.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
10.No plans to undergo bariatric surgery during the trial
11.Fundoscopy at screening without signs/symptoms of intracranial hypertension or diabetic retinopathy stage 2 / moderate or above or any other retinal disease contraindicated to growth hormone therapy. For subjects with a diagnosis of diabetes mellitus at screening, this must be documented with a fundus photograph
12.Serum fT4 in the normal range at screening as measured by central laboratory

Exclude criteria

A.For Subjects who participated in TCH-306
1. Diabetes mellitus if any of the following are met:
a. Poorly controlled diabetes, defined as HbA1C higher than 7.5% according to central laboratory at Visit 6 in trial TCH-306
b. Use of diabetes mellitus drugs other than metformin and/or dipeptidyl peptidase-4 (DPP-4) inhibitors
2. Active malignant disease
3. Known history of hypersensitivity and/or idiosyncrasy to the investigational product (somatropin or excipients)
4. Female who is pregnant, plans to become pregnant, or is breastfeeding
5. Female participant of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) not willing throughout the trial to use contraceptives as required by local law or practice.
6. Male participant not willing throughout the trial to use contraceptives as required by local law or practice.
7. Any disease or condition that, in the judgement of the investigator, may make the participant unlikely to comply with the requirements of the protocol or any condition that presents undue risk from the investigational product or trial procedures
8.eGFR <60 mL/min/1.73m2 determined based on Modification of Diet in Renal Disease (MDRD) equation using serum creatinine from the central laboratory at screening
9.Hepatic transaminases (ie, AST or ALT) >3 times the upper limit of normal according to the central laboratory at screening
B.For Subjects who are switching from commercially available daily somatropin treatment (Japan only)
1.Known Prader-Willi Syndrome and/or other genetic diseases that may have an impact on an endpoint.
2.Diabetes mellitus at screening if any of the following criteria are met:
a.Poorly controlled diabetes mellitus, 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 mellitus regimen (includes dose adjustment) within <90 days prior and throughout screening
d.Use of any diabetes mellitus 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 mellitus-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 for intracranial malignant tumors
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.eGFR <60 mL/min/1.73m2 determined based on Modification of Diet in Renal Disease (MDRD) equation using serum creatinine from the central laboratory at screening.
9.Hepatic transaminases (ie, AST or ALT) >3 times the upper limit of normal according to the central laboratory at screening.
10.Heart failure NYHA class 3 or greater (NYHA 1994).
11.QTcF >=451 milliseconds on 12-lead ECG at screening.
12.Poorly controlled hypertension, defined as supine systolic blood pressure >159 mmHg and/or supine diastolic blood pressure >95 mmHg at screening
13.Cerebrovascular accident within 5 years prior to screening.
14.Anabolic steroids (other than gonadal steroid replacement therapy) or oral/intravenous/intramuscular corticosteroids (other than in replacement or stress doses as described in Inclusion Criteria, part B, inclusion No.6) within 90 days prior to or throughout screening.
15.Currently using or have used within 26 weeks prior to screening any weight-loss or appetite-suppressive medications including orlistat, zonisamide, lorcaserin, bupropion, topiramate, sibutramine, stimulants (eg, phentermine or ADHD medications such as methylphenidate or amphetamines), GLP-1 receptor agonists (eg, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide), SGLT2 inhibitors (eg, canagliflozin, dapagliflozin, empagliflozin, sotagliflozin).
16.Known history of hypersensitivity and/or idiosyncrasy to any of the test compounds (somatropin) or excipients employed in this trial.
17.Known history of neutralizing anti-hGH antibodies.
18.Inability to undergo scanning by DXA or a non-interpretable DXA scan at screening.
19.Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) and not using adequate contraceptive methods
20.Male subjects must use a condom, or his female partner of childbearing potential must use an effective form of contraception as described above, from the beginning of screening to the last trial visit.
21.Known substance abuse or known (or previous) eating disorders, including anorexia nervosa, bulimia and severe gastrointestinal disease affecting normal eating (as judged by the investigator).
22.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.
23.Participation in another interventional clinical trial involving an investigational compound within 26 weeks prior to screening or in parallel to this trial.
24.Currently using or have used within the last 3 days prior to screening: biotin >0.03 mg/day from supplements
25.Known history of positive results of tests for human immunodeficiency virus (HIV) antibodies or hepatitis B and/or C (exceptions if vaccinated towards Hepatitis B virus)
26.Any of the following: acute critical illness, and complications following open heart surgery, abdominal surgery, multiple accidental traumas, acute respiratory failure, or similar conditions within 180 days prior to screening.

Related Information

• Primary Sponsor: Beckert Michael
• Secondary ID(s): NCT05171855