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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 (foresiGHt)

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ClinicalTrials.gov Identifier: NCT04615273
Recruitment Status : Recruiting
First Posted : November 4, 2020
Last Update Posted : February 23, 2021
Sponsor:
Information provided by (Responsible Party):
Ascendis Pharma A/S ( Ascendis Pharma Endocrinology Division A/S )

Brief Summary:
A 38 week dosing trial of lonapegsomatropin, a long-acting growth hormone product, administered once-a-week versus placebo-control. A daily somatropin product arm is also included to assist clinical judgement on the trial results. Approximately 240 adults (males and females) with growth hormone deficiency will be included. Randomization will occur in a 1:1:1 ratio (lonapegsomatropin : placebo). This is a global trial that will be conducted in, but not limited to, the United States, Europe, and Asia.

Condition or disease Intervention/treatment Phase
Growth Hormone Deficiency Endocrine System Diseases Hormone Deficiency Drug: Lonapegsomatropin Other: Placebo Drug: Somatropin Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, placebo-controlled, parallel group with subjects randomized into 3 treatment groups (1:1:1); lonapegsomatropin once-weekly, placebo for lonapegsomatropin once-weekly, somatropin daily.
Masking: Double (Participant, Investigator)
Masking Description: Once-weekly lonapegsomatropin and once-weekly placebo treatment arms will be double-blinded, daily somatropin product will be open-label.
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 3, 2020
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2024


Arm Intervention/treatment
Experimental: Lonapegsomatropin
Lonapegsomatropin administered once-weekly by subcutaneous injection
Drug: Lonapegsomatropin
Due to the different hGH dose requirements, depending on subject's age and concomitant use of oral estrogen, this trial has 3 dosing groups per arm, followed by gradual increasing dose titration to a target maintenance dose.

Placebo Comparator: Placebo
Placebo for Lonapegsomatropin administered once-weekly by subcutaneous injection
Other: Placebo
The placebo for lonapegsomatropin drug product will contain the same excipients as lonapegsomatropin drug product but does not contain lonapegsomatropin itself. The placebo solution will be administered by SC injection via syringe and needle. Due to the different hGH dose requirements, depending on subject's age and concomitant use of oral estrogen, this trial has 3 dosing groups and the placebo will receive the same dose volume as if they would have been randomized to once-weekly lonapegsomatropin.

Active Comparator: Somatropin
Somatropin administered once-daily by subcutaneous injection
Drug: Somatropin
Somatropin solution is provided in a pre-filled pen intended for daily subcutaneous injection. Due to the different hGH dose requirements, depending on subject's age and concomitant use of oral estrogen, this trial has 3 dosing groups per arm, followed by gradual increasing dose titration to a target maintenance dose.




Primary Outcome Measures :
  1. Change from Baseline in Trunk Percent Fat [ Time Frame: 38 weeks ]
    Change from baseline in trunk percent fat (as assessed by dual-energy x ray absorptiometry [DXA]) at Week 38


Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 38 weeks ]
    To evaluate the safety and tolerability of once-weekly lonapegsomatropin in adults with GHD

  2. Evaluate serum hGH, lonapegsomatropin, and mPEG levels [ Time Frame: 38 weeks ]
    To evaluate the pharmacokinetics (PK) of once-weekly lonapegsomatropin in adults with GHD

  3. Evaluate serum IGF-1 and IGFBP-3 and IGF-1 SDS and IGFBP-3 SDS [ Time Frame: 38 weeks ]
    To evaluate the pharmacodynamics (PD) of once-weekly lonapegsomatropin in adults with GHD

  4. Change from Baseline in Trunk Fat Mass [ Time Frame: 38 weeks ]
    Change from baseline in trunk percent fat (as assessed by dual-energy x ray absorptiometry [DXA]) compared to daily Somatropin at Week 38

  5. Change from Baseline in Total Body Lean Mass [ Time Frame: 38 weeks ]
    Change from baseline in total body lean mass (as assessed by dual-energy x ray absorptiometry [DXA]) compared to daily Somatropin at Week 38



Information from the National Library of Medicine

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Ages Eligible for Study:   23 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

    A. For all countries except Japan: Subjects must satisfy at least one of the following criteria:

    1. Insulin tolerance test: peak GH ≤5 ng/mL
    2. 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
    3. Three or four pituitary axis deficiencies (i.e., adrenal, thyroid, gonadal, and/or vasopressin; not including GH) with IGF-1 SDS ≤ -2.0 at screening
    4. Macimorelin test: peak GH ≤2.8 ng/mL
    5. 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:

    1. Insulin tolerance test: peak GH ≤1.8 ng/mL
    2. Glucagon test: peak GH ≤1.8 ng/mL
    3. 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 (e.g., 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.
  7. For males not on testosterone replacement therapy: morning (6:00 - 10:00AM) total testosterone within normal limits for age.
  8. 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.
  9. No plans to undergo bariatric surgery during the trial.
  10. Normal fundoscopy at screening (without signs/symptoms of intracranial hypertension or diabetic retinopathy above stage 2 / moderate). 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 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.
  2. Diabetes mellitus at screening if any of the following criteria are met:

    1. Poorly controlled diabetes, defined as HbA1c >7.5% at screening.
    2. 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
    3. Change in diabetes regimen (includes dose adjustment) within <90 days prior and throughout screening
    4. 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
    5. Diabetes-related complications at screening (i.e., 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:

    1. Resection of in situ carcinoma of the cervix uteri
    2. Complete eradication of squamous cell or basal cell carcinoma of the skin
    3. 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. eGFR <60 mL/min/1.73m2 determined based on Modification of Diet in Renal Disease (MDRD) equation.
  9. Hepatic transaminases (i.e., AST or ALT) >3 times the upper limit of normal.
  10. Heart failure NYHA class 3 or greater (NYHA 1994).
  11. QTcF ≥ 451 milliseconds on 12-lead ECG at screening.
  12. Poorly controlled hypertension.
  13. Cerebrovascular accident within 5 years prior to screening.
  14. Anabolic steroids (other than gonadal steroid replacement therapy) or oral/intravenous/intramuscular corticosteroids 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.
  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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04615273


Contacts
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Contact: Michael Beckert, MD +49 172-155-2596 mb@ascendispharma.com
Contact: Aimee D Shu, MD +1 650-461-4835 ads@ascendispharma.com

Locations
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United States, California
Ascendis Pharma Investigational Site Recruiting
Fresno, California, United States, 93720
Ascendis Pharma Investigational Site Recruiting
Los Angeles, California, United States, 90095
United States, Indiana
Ascendis Pharma Investigational Site Recruiting
Indianapolis, Indiana, United States, 46202
United States, Michigan
Ascendis Pharma Investigational Site Recruiting
Dearborn, Michigan, United States, 48126
United States, Nevada
Ascendis Pharma Investigational Site Recruiting
Las Vegas, Nevada, United States, 89148
Ascendis Pharma Investigational Site Recruiting
Reno, Nevada, United States, 89511
United States, New York
Ascendis Pharma Investigational Site Recruiting
New York, New York, United States, 10016
United States, North Carolina
Ascendis Pharma Investigational Site Not yet recruiting
Morehead City, North Carolina, United States, 28557
United States, Oregon
Ascendis Pharma Investigational Site Not yet recruiting
Portland, Oregon, United States, 92739
United States, Pennsylvania
Ascendis Pharma Investigational Site Recruiting
Pittsburgh, Pennsylvania, United States, 15212
United States, Texas
Ascendis Pharma Investigational Site Recruiting
Dallas, Texas, United States, 75390
Ascendis Pharma Investigational Site Recruiting
Houston, Texas, United States, 77074
Ascendis Pharma Investigational Site Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Ascendis Pharma Endocrinology Division A/S
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Responsible Party: Ascendis Pharma Endocrinology Division A/S
ClinicalTrials.gov Identifier: NCT04615273    
Other Study ID Numbers: TCH-306
2020-000929-42 ( EudraCT Number )
First Posted: November 4, 2020    Key Record Dates
Last Update Posted: February 23, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ascendis Pharma A/S ( Ascendis Pharma Endocrinology Division A/S ):
Lonapegsomatropin
Human Growth Hormone
hGH
rhGH
GHD
Adult Growth Hormone Deficiency
Long Acting Growth Hormone
Prodrug
Growth Failure
Growth Hormone Replacement Therapy
Sustained Release Growth Hormone
Growth Hormone Deficiency
TransCon hGH
Additional relevant MeSH terms:
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Dwarfism, Pituitary
Endocrine System Diseases
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases