Safety and Efficacy of Pegvisomant in Children With Growth Hormone Excess

Eligibility Criteria

• * Subjects who are eligible for enrollment must meet the following eligibility criteria:
• * 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 Principal Investigator. 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.
• * Stable dose/frequency of other medications for the treatment of GH excess for at least 3 months prior to initiation of pegvisomant and no further adjustment or addition of new medication for the duration of the study.
• * 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.
• * 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 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.