A Study Comparing the Safety and Effectiveness of Lonapegsomatropin with Placebo and Somatropin in Adults with Growth Hormone Deficiency

Overview

About this study

The purpose of this study is to evaluate the efficacy of once-weekly lonapegsomatropin compared to placebo at 38 weeks in adults with growth hormone deficiency (GHD).

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:
1. Age between 23 and 80 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 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
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.

Note: GH secretagogue product used in connection with stimulation tests for diagnosis of GHD is permitted (eg, macimorelin).

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.Note: Short-term increases in glucocorticoid doses taken on an as -needed basis for adrenal insufficiency are permitted (“stress dose” allowance: duration up to 5 days up to 2 times in 6 weeks, the maximum dose may reach 3 times the stable dose). One-time dose increases for diagnostic or other medical procedures are allowed.

Note: For subjects receiving oral estrogen or estrogen-containing therapy, subjects must intend to maintain the same dose and route of estrogen administration throughout the trial. For subjects receiving non-oral estrogen or estrogen-containing therapy, the dose may be adjusted as required, however subjects must intend to maintain the same route of administration throughout the trial.

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 μg/dL (measured at central laboratory) and/or Adrenocorticotrophic Hormone (ACTH) stimulation test or ITT with serum cortisol >18.0 μg/dL at or within 90 days prior to screening. Stimulation test protocols and results are subject to review and approval by the Medical Monitor.
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. 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.
11. Able and willing to provide a written ICF and authorization for protected health information (PHI) disclosure in accordance with Good Clinical Practice (GCP).
12. Serum fT4 in the normal range at screening as measured by central laboratory.
 

Exclusion Criteria:
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, 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 for intracranial malignant tumors
4. Evidence of growth of pituitary adenoma or other benign intracranial tumor within the last 12 months before screening.

Note: Absence of tumor growth is determined by comparison of two MRI or Computed Tomography (CT) scans; the most recent MRI or CT scan must be performed within 6 months prior to screening, and the interval between the two assessments must be at least 9 months. If MRI/CT scan within 6 months prior to screening is not available, it can be performed during screening.

Note: In subjects with no evidence of residual tumor or no prior history of intracranial tumor, one MRI/CT scan performed within 6 months prior to screening or during screening will suffice to confirm tumor absence.

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.

Note: If the initial measurement is out of range, the assessment should be repeated 2 more times and the average QTcF value should be used to determine the subject’s eligibility.

12. Poorly controlled hypertension, defined as supine systolic blood pressure >159 mmHg and/or supine diastolic blood pressure >95 mmHg at screening

Note: if the initial measurement is out of range, may be repeated 2 more times after 15 min and exclusion will be based on the average of the three measurements.

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 Criterion No.5) within 90 days prior to or throughout screening.

Note: Stable doses of inhaled, intra-articular, or topical corticosteroids are permitted.

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), SGLT-2 inhibitors (eg, canagliflozin, dapagliflozin, empagliflozin, sotagliflozin).

Note: if it can be documented that no weight-loss occurred with these drugs, a 90-day withdrawal period prior to screening is sufficient.

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 postmenopausal unless permanently sterile) and not using adequate contraceptive methods
     • Acceptable highly effective methods of contraception include intrauterine device (IUD); intrauterine system (IUS); bilateral tubal occlusion (must be documented); combined or progestogen-only hormonal contraception associated with inhibition of ovulation;           vasectomized partner (must be documented); or sexual abstinence (only when it is the usual and preferred lifestyle of the subject).
     • Clinically acceptable methods of birth control include male or female condom with or without spermicide; progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action; or cap, diaphragm, or sponge with spermicide.
     • Permanent sterilization includes hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.

Note: Females of childbearing potential must accept to use the above-mentioned methods of contraception from the beginning of screening to the last trial visit.

Note: Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods)and withdrawal are not acceptable methods of contraception.

Note: For subjects using oral combined hormonal contraception (ie containing estrogen), the dose and route must be stable for ≥6 weeks prior to screening and throughout the trial

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 and Hepatitis C 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.

Note: For France, all categories of protected persons specified in the Public Health Code are excluded from participation.

Eligibility last updated 01/05/2022. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Irina Bancos, M.D.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Department of Medicine (DOM) Research Hub

(507) 266-1944

DOMRESEARCHHUB@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20513445

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