A Post-Marketing Study of the Immunogenicity of Somatropin (Ribosomal Deoxyribo Nucleic Acid [rDNA] Origin) Injection (Nutropin AQ®) in Children With Growth Hormone Deficiency

A Phase IV, Multicenter, Open-Label Study of the Immunogenicity of Nutropin AQ® V1.1 [Somatropin (rDNA Origin) Injection] Administered Daily to Naïve Growth Hormone-Deficient Children (iSTUDY)

This is a Phase IV, multicenter, open-label, single-arm study of somatropin (rDNA origin) (Nutropin AQ v1.1) in pre-pubertal children with growth hormone deficiency (GHD) naïve to prior recombinant human growth hormone (rhGH) treatment. The study is designed to characterize the immunogenicity profile of somatropin (rDNA origin) injection when administered daily subcutaneously for 12 months. The clinical impact of immunogenicity will also be assessed.

Study Overview

• Status: Completed
• Conditions: Growth Hormone Deficiency
• Intervention / Treatment: Drug: Somatropin

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital Research Institute
  • California
    • Orange, California, United States, 92868-3874
      • Children's Hospital of Orange County
    • Sacramento, California, United States, 95821
      • Center of Excellence in Diabetes & Endocrinology
    • San Diego, California, United States, 92123
      • San Diego Medical Group; Pediatric Endocrinology
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Rocky Mountain Pediatric Endocrinology, PC
    • Greenwood Village, Colorado, United States, 80111
      • Pediatric Endocrine Associates
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic - of the Nemours Foundation
    • Miami, Florida, United States, 33155-3009
      • Miami Children's Hospital
    • Orlando, Florida, United States, 32801
      • Nemours Childrens Clinic
    • Tallahassee, Florida, United States, 32308
      • The Pediatric Endocrine Office of Larry C. Deeb
    • Tampa, Florida, United States, 33612
      • USF Diabetes Center
    • Tampa, Florida, United States, 33607
      • Pediatric Endrocine Assoc
  • Georgia
    • Atlanta, Georgia, United States, 20010
      • Emory Children's Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Barry J Reiner, MD, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Childrens Hospital
    • Springfield, Massachusetts, United States, 01199
      • Baystate Endocrinology and Diabetes; Baystate Children's Specialty Center, Pediatric Endocrinology
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0934
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Childrens' Hospital
    • Saint Paul, Minnesota, United States, 55102
      • Children's Healthcare d.b.a Children's Hospitals and Clinics of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospitals & Clinics; Pulmonology
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center PARTNER
  • New York
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC General Pediatrics Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Milton S Hershey Ped Sub Spclt
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina; MUSC Pediatric Endocrinology
  • Texas
    • Dallas, Texas, United States, 75231
      • Endocrine Associates of Dallas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Hospital
  • Washington
    • Tacoma, Washington, United States, 98405
      • Multicare Institute for Research and Innovation
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 14 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Bone age less than equal to (</=) 9 years (females) or </= 11 years (males) as determined by X-ray of the left hand and wrist using Greulich and Pyle method and obtained within the 12 months prior to enrollment
• Prepubertal (Tanner I) males and females by physical examination
• Diagnosis of GHD (stimulated GH less than [<] 10 nanograms per milliliter [ng/mL]) by two standard pharmacologic tests obtained up to 12 months prior to informed consent/assent
• Normal thyroid function test within the 12 months prior to informed consent/assent
• Normal complete blood counts within 12 months prior to informed consent/assent
• Documentation of prior height and weight measurements, with height standard deviation score (SDS) </= 5th percentile for idiopathic isolated GHD participants

Exclusion Criteria:

• Any previous rhGH treatment
• Short stature etiologies other than GHD
• Acute critical illness or uncontrolled chronic illness, which in the opinion of the investigator and medical monitor, would interfere with participation in this study, interpretation of the data, or pose a risk to participant safety
• Chronic illnesses such as inflammatory bowel disease, celiac disease, heart disease, and diabetes
• Bone diseases such as achondroplasia or hypochondroplasia, intracranial tumor, irradiation, and traumatic brain injury
• Participants receiving oral or inhaled chronic corticosteroid therapy (greater than [>] 3 months) for other medical conditions other than central adrenal insufficiency
• Participants who require higher (2 times or greater than maintenance) doses of corticosteroids for more than 5 days in the 6 months prior to enrollment in the study
• Participants with active malignancy or any other condition that the investigator believes would pose a significant hazard to the participant if rhGH were initiated
• Females with Turner syndrome regardless of their GH status
• Prader-Willi syndrome regardless of GH status
• Born small for gestational age regardless of GH status
• Presence of scoliosis requiring monitoring
• Previous participation in another clinical trial or investigation of GH, treatment for growth failure, or treatment with a biologic agent
• Participants with closed epiphyses
• Participants with a known hypersensitivity to somatropin, excipients, or diluent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Somatropin; Children will receive daily SC injections of somatropin at a dose of up to 0.043 milligrams per kilogram per day (mg/kg/day) for 1 year.	Drug: Somatropin; Somatropin will be administered as SC injections at a dose of up to 0.043 mg/kg/day. The dose may be adjusted for a change in body weight of at least (plus [+]/minus [-]) 2 kilograms (kg) from baseline at the Month 6 study visit or for a change in insulin-growth factor-1 (IGF-1), as per investigator assessment.; Other Names: Nutropin AQ v1.1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Develop Anti-GH Antibodies After Treatment With Nutropin AQ v1.1	Participants who were tested positive to anti-GH antibody after initiation of study treatment.	Baseline up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Exhibit Functional Growth Attenuation	Growth attenuation is defined as initial growth response greater than pretreatment velocity followed by reduction in growth response to below the pretreatment velocity in the subsequent 6- to 12-month treatment period or reaching ≤ 2 cm per year.	Baseline up to 1 year
Percentage of Participants With Neutralizing Antibodies	Among participants who developed positive anti-GH antibody post-baseline, participants who were tested positive to neutralizing anti-GH antibody during study participation.	Baseline up to 1 year
Annualized Growth Velocity at Months 6 and 12 (Change From Baseline)	Annualized growth velocity is defined as (height - baseline height) / (date of height assessment - date of baseline)*365.25. Results are presented according to anti-GH antibody status (positive included all participants that were anti-GH antibody positive at least once post-baseline visit and anti-GH antibody negative population included all participants that were anti-GH antibody negative at all post-baseline visits).	Months 6, 12
Height Standard Deviation Score (SDS) at Months 6 and 12 (Change From Baseline)	Height Standard Deviation Score (SDS) allows for the comparison of a participants height to that of others in the same age group. Therefore, the average height for that age group will have the SDS of 0. In this study, the starting Height SDS score was ≤ -1.5 (≤ 5th percentile). Results are presented according to anti-GH antibody status (positive included all participants that were anti-GH antibody positive at least once post-baseline visit and anti-GH antibody negative population included all participants that were anti-GH antibody negative at all post-baseline visits.	Months 6, 12
Percentage of Participants With Adverse Events	Among participants who received at least one dose of study drug, those who reported at least one adverse event during study participation.	Baseline up to 1 year

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 31, 2015
• Primary Completion (ACTUAL): November 8, 2017
• Study Completion (ACTUAL): November 8, 2017

Study Registration Dates

• First Submitted: December 4, 2014
• First Submitted That Met QC Criteria: December 8, 2014
• First Posted (ESTIMATE): December 9, 2014

Study Record Updates

• Last Update Posted (ACTUAL): January 8, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Dwarfism, Pituitary
• Other Study ID Numbers: ML29543