A Trial to Compare the Efficacy and Safety of Once-weekly Lonapegsomatropin With Placebo and a Daily Somatropin Product in Adults With Growth Hormone Deficiency

Inclusion Criteria

• Age between 23 and 80 years, inclusive, at screening.
• Adult Growth Hormone Deficiency (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).
• Participants with childhood-onset GHD must have had GH axis re-assessed at final height.
• In participants with TBI as a cause of GHD, GHD must be confirmed by GH -stimulation testing performed at least 12 months after the injury.

A. For all countries except Japan: participants must have satisfied at least one of the following criteria:

• Insulin tolerance test: peak growth hormone (GH) 30 kg/m^2: peak GH =25- 30 kg/m^2, peak GH =6 weeks prior to and throughout screening.
• For participants not on glucocorticoid replacement therapy, documentation of adequate adrenal function at screening defined as: morning (6:00-10:00 AM) serum cortisol >15.0 mcg/dL (measured at central laboratory) and/or adrenocorticotropic hormone (ACTH) stimulation test or insulin tolerance test with serum cortisol >18.0 mcg/dL at or within 90 days prior to screening.
• For males not on testosterone replacement therapy: morning (6:00 - 10:00AM) total testosterone within normal limits for age.
• On a stable diet and exercise regime at screening with no intention to modify diet or exercise pattern during the trial, i.e., no weight reduction program intended during the trial or within the last 90 days prior to or through screening.
• No plans to undergo bariatric surgery during the trial.
• Fundoscopy at screening without signs/symptoms of intracranial hypertension or diabetic retinopathy above stage 2 / moderate or above or any other retinal disease contraindicated to growth hormone therapy. For participants with a diagnosis of diabetes mellitus at screening, this must be documented with a fundus photograph.
• Able and willing to provide a written informed consent and authorization for protected health information (PHI) disclosure in accordance with Good Clinical Practice (GCP).
• Serum free thyroxine (fT4) in the normal range at screening as measured by central laboratory.

Exclusion Criteria

• Known Prader-Willi Syndrome and/or other genetic diseases that may have an impact on an endpoint.
• Diabetes mellitus at screening if any of the following criteria are met:
• Poorly controlled diabetes, defined as HbA1c >7.5% at screening.
• 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 3 times the upper limit of normal.
• Heart failure New York Heart Association (NYHA) class 3 or greater (NYHA 1994).
• Q-T interval, corrected by Fridericia's method (QTcF) >= 451 milliseconds on 12-lead electrocardiogram (ECG) at screening.
• Poorly controlled hypertension, defined as supine systolic blood pressure >159 mmHg and/or supine diastolic blood pressure >95 mmHg at screening.
• Cerebrovascular accident within 5 years prior to screening.
• Anabolic steroids (other than gonadal steroid replacement therapy) or oral/intravenous/intramuscular corticosteroids within 90 days prior to or throughout screening.
• 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, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-dependent glucose cotransporters (SGLT-2) inhibitors or medications that affects IGF-1 or GH measurements including cabergoline at doses above 0.5 mg weekly or bromocriptine at doses above 20 mg weekly.
• Known history of hypersensitivity and/or idiosyncrasy to any of the test compounds (somatropin) or excipients employed in this trial.
• Known history of neutralizing anti