Back to resultsA Post-Marketing Study of the Immunogenicity of Somatropin (Ribosomal Deoxyribo Nucleic Acid [rDNA] Origin) Injection (Nutropin AQ®) in Children With Growth Hormone Deficiency
Primary Purpose
Growth Hormone Deficiency
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Somatropin
Sponsored by
About this trial
This is an interventional treatment trial for Growth Hormone Deficiency
Eligibility Criteria
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
Sites / Locations
- Arkansas Children's Hospital Research Institute
- Children'S Hospital of Orange County
- Center of Excellence in Diabetes & Endocrinology
- San Diego Medical Group; Pediatric Endocrinology
- Rocky Mountain Pediatric Endocrinology, PC
- Pediatric Endocrine Associates
- Nemours Children's Clinic - of the Nemours Foundation
- Miami Children's Hospital
- Nemours Childrens Clinic
- The Pediatric Endocrine Office of Larry C. Deeb
- Pediatric Endrocine Assoc
- USF Diabetes Center
- Emory Children's Center
- University of Louisville
- Barry J Reiner, MD, LLC
- Boston Childrens Hospital
- Baystate Endocrinology and Diabetes; Baystate Children's Specialty Center, Pediatric Endocrinology
- University of Michigan
- University of Minnesota Childrens' Hospital
- Children's Healthcare d.b.a Children's Hospitals and Clinics of Minnesota
- Children's Mercy Hospitals & Clinics; Pulmonology
- Hackensack University Medical Center PARTNER
- New York Presbyterian Hospital
- UNC General Pediatrics Clinic
- University of Oklahoma Health Sciences Center
- Oregon Health and Science University
- Milton S Hershey Ped Sub Spclt
- Thomas Jefferson University Hospital
- Medical University of South Carolina; MUSC Pediatric Endocrinology
- Endocrine Associates of Dallas
- Cook Children's Hospital
- MultiCare Health System Institute for Research and Innovation
- MultiCare Institute for Research and Innovation
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Somatropin
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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).
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02311894
Brief Title
A Post-Marketing Study of the Immunogenicity of Somatropin (Ribosomal Deoxyribo Nucleic Acid [rDNA] Origin) Injection (Nutropin AQ®) in Children With Growth Hormone Deficiency
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)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
March 31, 2015 (Actual)
Primary Completion Date
November 8, 2017 (Actual)
Study Completion Date
November 8, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Growth Hormone Deficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Somatropin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Somatropin
Other Intervention Name(s)
Nutropin AQ v1.1
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Develop Anti-GH Antibodies After Treatment With Nutropin AQ v1.1
Description
Participants who were tested positive to anti-GH antibody after initiation of study treatment.
Time Frame
Baseline up to 1 year
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Exhibit Functional Growth Attenuation
Description
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.
Time Frame
Baseline up to 1 year
Title
Percentage of Participants With Neutralizing Antibodies
Description
Among participants who developed positive anti-GH antibody post-baseline, participants who were tested positive to neutralizing anti-GH antibody during study participation.
Time Frame
Baseline up to 1 year
Title
Annualized Growth Velocity at Months 6 and 12 (Change From Baseline)
Description
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).
Time Frame
Months 6, 12
Title
Height Standard Deviation Score (SDS) at Months 6 and 12 (Change From Baseline)
Description
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.
Time Frame
Months 6, 12
Title
Percentage of Participants With Adverse Events
Description
Among participants who received at least one dose of study drug, those who reported at least one adverse event during study participation.
Time Frame
Baseline up to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Arkansas Children's Hospital Research Institute
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Children'S Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868-3874
Country
United States
Facility Name
Center of Excellence in Diabetes & Endocrinology
City
Sacramento
State/Province
California
ZIP/Postal Code
95821
Country
United States
Facility Name
San Diego Medical Group; Pediatric Endocrinology
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Rocky Mountain Pediatric Endocrinology, PC
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Pediatric Endocrine Associates
City
Greenwood Village
State/Province
Colorado
ZIP/Postal Code
80111
Country
United States
Facility Name
Nemours Children's Clinic - of the Nemours Foundation
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Miami Children's Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155-3009
Country
United States
Facility Name
Nemours Childrens Clinic
City
Orlando
State/Province
Florida
ZIP/Postal Code
32801
Country
United States
Facility Name
The Pediatric Endocrine Office of Larry C. Deeb
City
Tallahassee
State/Province
Florida
ZIP/Postal Code
32308
Country
United States
Facility Name
Pediatric Endrocine Assoc
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
USF Diabetes Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory Children's Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Barry J Reiner, MD, LLC
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
Boston Childrens Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Baystate Endocrinology and Diabetes; Baystate Children's Specialty Center, Pediatric Endocrinology
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0934
Country
United States
Facility Name
University of Minnesota Childrens' Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Children's Healthcare d.b.a Children's Hospitals and Clinics of Minnesota
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Children's Mercy Hospitals & Clinics; Pulmonology
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Hackensack University Medical Center PARTNER
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
UNC General Pediatrics Clinic
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Milton S Hershey Ped Sub Spclt
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Medical University of South Carolina; MUSC Pediatric Endocrinology
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Endocrine Associates of Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Cook Children's Hospital
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
MultiCare Health System Institute for Research and Innovation
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
MultiCare Institute for Research and Innovation
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Post-Marketing Study of the Immunogenicity of Somatropin (Ribosomal Deoxyribo Nucleic Acid [rDNA] Origin) Injection (Nutropin AQ®) in Children With Growth Hormone Deficiency
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