NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

19-CH-0071

Sponsoring Institute

National Institute of Child Health and Human Development (NICHD)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 2 Years
Max Age: 18 Years

Referral Letter Required

No

Population Exclusion(s)

None

Special Instructions

Currently Not Provided

Keywords

Pediatric;
Gigantism;
Growth Hormone

Recruitment Keyword(s)

None

Condition(s)

Pituitary Disease

Investigational Drug(s)

Pegvisomant

Investigational Device(s)

None

Intervention(s)

Drug: Pegvisomant

Supporting Site

National Institute of Child Health and Human Development

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.

--Back to Top--

Eligibility

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 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 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.

-Willingness to discontinue other medications for the treatment of GH excess for a 6-week washout period prior to initiating pegvisomant

-Able to provide consent/assent if developmentally appropriate

-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.

-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).

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 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.


--Back to Top--

Citations:

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.

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.

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.

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Christina Tatsi, M.D.
National Institute of Child Health and Human Development (NICHD)



Christina Tatsi, M.D.
National Institute of Child Health and Human Development (NICHD)
NIHBC 10 - CRC BG RM 1-3216
10 CENTER DR
BETHESDA MD 20892
(301) 451-7170
christina.tatsi3@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT03882034

--Back to Top--