An Open-Label Phase 3 Study of the Safety and Efficacy of Pegvisomant in Children With Growth Hormone Excess

  • End date
    Jan 1, 2024
  • participants needed
  • sponsor
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Updated on 12 October 2022
medical therapy
growth hormone
pituitary tumor
hand x-ray



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.


To test the role of pegvisomant in children and adolescents with gigantism.


People ages 2-18 with GH excess for whom usual treatments have not worked or who are not eliginle for them


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


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.



Study Description:

Growth hormone excess is a rare and potentially lethal condition associated with hypersecretion of growth hormone (GH), usually by a pituitary tumor or hyperplasia. When it occurs prior to the complete fusion of growth plates, it leads to pathological tall stature, and it is called gigantism. After the fusion of the growth plates, it is called acromegaly. It may be associated with debilitating cardiovascular disease and/or diabetes. Children and adolescents with gigantism are currently treated with surgery, radiation therapy, and medications, such as octreotide, to reduce hypersecretion of GH; however, these treatments may lack efficacy and have significant side effects. Pegvisomant is a genetically engineered GH-receptor (GHR) antagonist that blocks the action of GH. In adults with acromegaly, pegvisomant has been shown to effectively reduce serum insulin-like growth factor type 1 (IGF-1) concentrations and lead to clinical improvement. However, experience in children and adolescents is limited to a small number of case series.,We propose the initiation of a new protocol at the NICHD, NIH, to treat children and adolescents with GH excess that is refractory to surgical therapy and/or radiation therapy, or in children and adolescents where the above therapies are contraindicated.



  • Percent change of IGF-1 z-score from baseline to end of study (12 month visit).
  • Determine the safety and tolerability of pegvisomant in children and adolescents with GH excess.


Normalization of the IGF-1 for age and sex from baseline to end of study (normal value defined as +/- 2 SD from the mean). Change in growth velocity to a near-normal range (+/- 1 SD) according to the Tanner and Davies growth velocity curves for age, sex, and stage of puberty, when comparing the 6-month period prior to the study drug initiation to the growth velocity between 6 and 12 months on the study drug.

  • Improvement in signs and symptoms of GH excess that are common in the pediatric population (headaches, excessive perspiration, fatigue, increased appetite) and the quality of life of the patients from baseline to the end of the study (12 month visit).
  • Improvement of the cardiac structure and function: reduction of

the left ventricular mass index (LVMi), and change of the left

ventricular ejection fraction (EF) on echocardiogram from

baseline to the end of the study (12 month visit).

The objectives of the proposed study are to characterize the efficacy of pegvisomant as indicated by adequate control of the IGF-1 levels, the safety profile of the medication in children with GH excess, and to obtain pharmacodynamic data on the effect of pegvisomant on the GH-IGF axis in children. Because pegvisomant does not inhibit GH secretion, serum IGF-1 is the best marker of treatment efficacy. Pharmacokinetic (PK) studies will be performed in a subset of patients. This study will enroll patients younger than 18 years.

Endpoints: Safety

Patients who have received at least 1 dose of pegvisomant will be included in the safety evaluations.

Safety will be evaluated by:

  • Spontaneously reported adverse events
  • Vital signs and periodic physical examinations (performed at the Clinical Center at baseline, 6 months (if possible unless telehealth visit performed) and 12 months after the study enrollment, and at local provider s office at regular intervals between those visits)
  • Laboratory tests (performed periodically as indicated by previous studies and according to the timeline at page 10-11) including:
  • Hematology
  • Chemistry
  • Lipids
  • Liver function panel
  • Thyroid function tests
  • IGF-1
  • Glucose and insulin
  • MRI of the pituitary to check for tumor growth at baseline and 1 year
  • Annual liver ultrasound
  • ECG and echocardiogram at baseline, 6 months (EKG) and 1-year to monitor for the presence of cardiac arrhythmias and growth hormone related cardiomyopathy
  • Care providers will complete the Gigantism Symptoms Assessment Questionnaire (GSAQ) and Child Health Questionnaire by Landgraf & Wade for assessment of quality of life.
  • Patients with gigantism and diabetes mellitus may require careful monitoring and dose reductions of insulin and/or oral hypoglycemic agents as pegvisomant usually has beneficial effects on glucose metabolism.7 Patients with pre-existing diabetes will continue to monitor their daily blood glucose levels, as previously instructed, and communicate with the investigational team for persistent elevation or decrease of the glucose levels. The changes of the dose of the anti-diabetic drugs and/or insulin will be done with communication of the research team with the local endocrinologist. Patients without pre-existing diabetes will be educated on the signs of hyperglycemia and will get monthly fasting blood glucose level measurements for the first 6 months along with the screening of the liver enzyme levels.

We propose a 60-week (+/-2 weeks) study of once daily dosing of pegvisomant in children and adolescents ages 24 months to <18 years of age with gigantism. We propose the recruitment of up to 40 patients over the 3 years of the study.

Condition Pituitary Disease
Treatment pegvisomant
Clinical Study IdentifierNCT03882034
SponsorEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Last Modified on12 October 2022


Yes No Not Sure

Inclusion Criteria

Males and females 24 months to <18 years at informed consent
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/mL 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
Willingness to discontinue other medications for the treatment of GH excess for a 6-week washout period prior to initiating pegvisomant
secreting pituitary tumor, or inability to tolerate surgery or radiation
Able to provide consent/assent if developmentally appropriate
therapies or patient deemed inappropriate candidate for surgery and/or
Willing to use non-hormonal method of contraception in patients of reproductive potential. 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
pituitary radiation therapy, as determined by review of the medical records by
the Principal Investigator. The evaluation of the patient should be performed
Have a primary health care provider in home location who will perform regular height and weight measurements, vital signs, and safety labs
at least 3 months after the surgery date in order to ensure that there is
persistent GH excess after the transsphenoidal resection of the tumor. If the
patient has received irradiation, there is no minimium 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
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)

Exclusion Criteria

Liver function abnormalities (ALT, AST) greater than or equal to 3 times ULN
Positive pregnancy test in females, current pregnancy and/or female patients who are
Patients currently using opioids. Opioids induce altered metabolism of pegvisomant
Since this is a phase 3 study, opioids may affect the PK studies to be performed and
thus, chronic use of opioids (>2 weeks) will be an exclusion criterion
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
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