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

Growth Hormone Deficiency Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02311894
• Other study ID #: ML29543
• Status: Completed
• Phase: Phase 4
• Start date: March 31, 2015
• Est. completion date: November 8, 2017

Study information

• Verified date: December 2018
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: November 8, 2017
• Est. primary completion date: November 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 14 Years

Eligibility

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

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency

Intervention

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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory Children's Center	Atlanta	Georgia
United States	Barry J Reiner, MD, LLC	Baltimore	Maryland
United States	Boston Childrens Hospital	Boston	Massachusetts
United States	Rocky Mountain Pediatric Endocrinology, PC	Centennial	Colorado
United States	UNC General Pediatrics Clinic	Chapel Hill	North Carolina
United States	Medical University of South Carolina; MUSC Pediatric Endocrinology	Charleston	South Carolina
United States	Endocrine Associates of Dallas	Dallas	Texas
United States	Cook Children's Hospital	Fort Worth	Texas
United States	Pediatric Endocrine Associates	Greenwood Village	Colorado
United States	Hackensack University Medical Center PARTNER	Hackensack	New Jersey
United States	Milton S Hershey Ped Sub Spclt	Hershey	Pennsylvania
United States	Nemours Children's Clinic - of the Nemours Foundation	Jacksonville	Florida
United States	Children's Mercy Hospitals & Clinics; Pulmonology	Kansas City	Missouri
United States	Arkansas Children's Hospital Research Institute	Little Rock	Arkansas
United States	University of Louisville	Louisville	Kentucky
United States	Miami Children's Hospital	Miami	Florida
United States	University of Minnesota Childrens' Hospital	Minneapolis	Minnesota
United States	New York Presbyterian Hospital	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children'S Hospital of Orange County	Orange	California
United States	Nemours Childrens Clinic	Orlando	Florida
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Center of Excellence in Diabetes & Endocrinology	Sacramento	California
United States	Children's Healthcare d.b.a Children's Hospitals and Clinics of Minnesota	Saint Paul	Minnesota
United States	San Diego Medical Group; Pediatric Endocrinology	San Diego	California
United States	Baystate Endocrinology and Diabetes; Baystate Children's Specialty Center, Pediatric Endocrinology	Springfield	Massachusetts
United States	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington
United States	MultiCare Institute for Research and Innovation	Tacoma	Washington
United States	The Pediatric Endocrine Office of Larry C. Deeb	Tallahassee	Florida
United States	Pediatric Endrocine Assoc	Tampa	Florida
United States	USF Diabetes Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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