Safety and Efficacy of Pegvisomant in Children With Growth Hormone Excess

NCT03882034 | Completed Phase 3 FDA Drug

• 2 other identifiers: 19007119-CH-0071
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Background: For children with gigantism, too much growth hormone (GH) in the body causes abnormal growth and many other problems. Current treatments often don t work; no medical treatment is approved by FDA. Researchers want to see if the drug pegvisomant can help. Objective: To test the role of pegvisomant in children and adolescents with gigantism. Eligibility: People ages 2-18 with GH excess for whom usual treatments have not worked or who are not eliginle for them Design: Participants will be screened with a medical history. The study will last 60 weeks and include at least 3 visits: baseline, 6-month, and 12-month visits. For the baseline visit, participants will stay a few nights for testing. They may stay overnight for the other visits. All visits will include: Medical history Physical exam Questionnaires Heart and liver tests Participants may be photographed in their underwear if they agree. Blood tests: Participants will get a catheter: A small plastic tube will be placed in an arm vein. For some tests, the blood may be drawn every 30 minutes over 3 hours. For other tests, blood will be drawn every 20 minutes over 12 hours. Only clinically necessary tests will be done in each patient. At the baseline visit, participants will have the study drug injected under the skin. They will learn to take the injection at home. They will take the injection daily during the study. The baseline and 12-month visits will include: MRI: Participants will have a dye injected into a vein. They will lie in a machine that takes pictures of the body. Hand X-ray Participants must get their height and weight at their local doctor s office monthly. Participants must have blood and urine tests at their local lab monthly for the first 6 months then every 3 months until the study ends. ...

Conditions

Pituitary Disease

Keywords

Pediatric; Gigantism; Growth Hormone; Hormone; Pituitary Disease

Outcome Measures

Primary Outcomes (2)

• Percent change of IGF-1 z-score from baseline to end of study (12 month visit).

  The primary endpoint is decrease in IGF-1 z-score \>50% from baseline. This criterion will be used to determine efficacy.

  1 year

• Determine the safety and tolerability of pegvisomant in children with GH excess

  Safety will be determined by the periodical description of vital signs, laboratory and imaging studies, and other reported side effects.

  During 1 year

Secondary Outcomes (5)

• Normalization of IGF-1 for age and sex from baseline to end of study (12 month visit)

  1 year

• Normalization of growth velocity

  1 year

• Improvement in signs and symptoms of GH excess and quality of life from baseline to end of study (12 month visit)

  1 year

• Left ventricular ejection fraction change on echocardiogram from baseline to end of study (12 month visit).

  1 year

• Reduction of the left ventricular mass index (LVMi) on echocardiogram from baseline to end of study (12 month visit)

  1 year

Study Arms (1)

1

EXPERIMENTAL

Intervention arm, Patient received pegvisomant

Drug: Pegvisomant

Interventions

Pegvisomant DRUG

A fixed dose of pegvisomant 10-mg started on Day 1 of intervention and continued daily afterwards, will be administered subcutaneously according to manufacturer's recommendations. Adjustment of the dose will occur as per protocol.

1

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects who are eligible for enrollment must meet the following eligibility criteria:
• Cohort 1: Patients with GH excess
• Males and females 24 months to \<18 years at enrollment
• Active GH excess as demonstrated by the following:
• IGF-1 greater than the upper limit of normal for age and sex during screening (\>+2 SD) and
• Abnormal GH levels as demonstrated by inability to suppress to \<1 ng/mLwith older radioimmunoassays or \<0.4ng/ml with sensitive immunoradiometric or immunochemiluminescent assays within 2 hours during Oral Glucose Tolerance Test (OGTT) after the administration of 1.75gr/kg (max 75gr) of glucose or elevated GH secretion profile during overnight sampling.
• History of inadequate response to trans-sphenoidal surgery or radiation therapy for GH secreting pituitary tumor, or inability to tolerate surgery or radiation therapies or patient deemed inappropriate candidate for surgery and/or pituitary radiation therapy, as determined by review of the medical records by the PI. The evaluation of the patient should be performed at 3 months after the surgery date in order to ensure that there is persistent GH excess after the transsphenoidal resection of the tumor unless there are clear evidence of persistent disease, e.g. residual tumor, based on the PI s assessment. If the patient has received irradiation, there is no minimum time to be considered before enrolling in the study. The effects of radiation therapy take place over many years after receiving it (mean time to remission for stereotactic radiation therapy of 12-60 months), and, thus, a medical therapy is required during that period.
• Patient is either not receiving any other medication for GH excess or is receiving stable dose/frequency of other medications for the treatment of GH excess prior to initiation of pegvisomant and no further adjustment or addition of new medication is made for the duration of the study.
• Medications that may be co-administered for GH excess include but are not limited to: IM/SC/oral first- or second-generation somatostatin analogues (octreotide, lanreotide, pasireotide), oral dopamine agonist (cabergoline) and any other medication/formulation that may become available during this study. For each medication, its specific formulation and route of administration, patient will need to be on stable dose/frequency for a duration that is at least the minimum time recommended for adjusting the dose by the manufacturer which usually incorporates the time needed to reach plasma steady-state levels and a new plateau on the effect of the medication on IGF-1 (cabergoline: 4 weeks; SC octreotide/pasireotide administered twice or three times daily: 2 weeks; oral octreotide: 2 weeks; depot IM octreotide/SC lanreotide/IM pasireotide administered Q4 weeks: 3 months). The duration needed for the stable dose for patients on alternative schedules of administration of the above or other medications will be assessed based on available information and the longest estimated interval to achieve the full effect.
• If a patient has been receiving a medication for GH excess but is not interested to continue that medication a minimum period of 6-weeks of discontinuation of the medication will be required for washout. This period was defined in the prior version of the protocol and is designed to minimize the time the patient may not be receiving any treatment for GH excess.
• Able to provide consent/assent if developmentally appropriate
• Willing to use non-hormonal method of contraception in patients of reproductive potential from the start of the study until at least 28 days after they stop the medication. Females of reproductive age (Tanner 3 or more, and/or having menstrual cycle) will be educated on the risks of unknown potential fetal harm while using the investigational medication, and they will be educated on the alternative preventative methods for contraception (condoms). Females already receiving oral contraceptive pills (OCPs) will be evaluated by gynecology consult service to discuss effective non-hormonal contraception. Sexually active female subjects must agree to use an effective non-hormonal contraception for the duration of the study.
• Have a primary health care provider in home location who will perform regular height and weight measurements, vital signs, and safety labs.
• Height and weight will be requested to be performed according to the published methods included in the CDC-NHANES manual on anthropometry procedures manual (Supplementary Material). They will be plotted on the respective growth charts produced by the CDC for the US population (Supplementary Material).
• Cohort 2: Parents

You may not qualify if:

• Cohort 1: Patients
• An individual who meets any of the following criteria will be excluded from participation in this study:
• Liver function abnormalities (ALT, AST) greater than or equal to 3 x ULN
• Positive pregnancy test in females, current pregnancy and/or female patients who are breastfeeding.
• Patients with any medical, physical, psychiatric, or social condition, which, in the opinion of the investigators, would make participation in this protocol not in their best interest, will be excluded from the study. Patients who are critically ill, unstable, or with severe organ failure that may affect/limit the endocrine evaluation and place unsustainable demands on CC or NICHD resources will be excluded.
• Cohort 2: Patients Parents:

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, Dimaraki EV, Stewart PM, Friend KE, Vance ML, Besser GM, Scarlett JA, Thorner MO, Parkinson C, Klibanski A, Powell JS, Barkan AL, Sheppard MC, Malsonado M, Rose DR, Clemmons DR, Johannsson G, Bengtsson BA, Stavrou S, Kleinberg DL, Cook DM, Phillips LS, Bidlingmaier M, Strasburger CJ, Hackett S, Zib K, Bennett WF, Davis RJ. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med. 2000 Apr 20;342(16):1171-7. doi: 10.1056/NEJM200004203421604.

  PMID: 10770982 BACKGROUND

• Lodish MB, Trivellin G, Stratakis CA. Pituitary gigantism: update on molecular biology and management. Curr Opin Endocrinol Diabetes Obes. 2016 Feb;23(1):72-80. doi: 10.1097/MED.0000000000000212.

  PMID: 26574647 BACKGROUND

• Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA; Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Nov;99(11):3933-51. doi: 10.1210/jc.2014-2700. Epub 2014 Oct 30.

  PMID: 25356808 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pituitary Diseases; Gigantism

Interventions

pegvisomant

Condition Hierarchy (Ancestors)

Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hyperpituitarism

Study Officials

• Karim A Calis, Pharm.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: March 20, 2019
• Study Start: October 21, 2019
• Primary Completion: September 8, 2025
• Study Completion: September 30, 2025
• Last Updated: November 6, 2025

Record last verified: 2025-11-04

Locations

US (1)