NCT02311894

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

Completed Phase 4 Results posted Last updated 8 January 2019

What this trial tests

Phase 4 trial testing Somatropin in Growth Hormone Deficiency in 82 participants. Completed in 8 November 2017.

Timeline

31 March 2015

Primary endpoint
8 November 2017

8 November 2017

Quick facts

Lead sponsor	Genentech, Inc.
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	82
Start date	31 March 2015
Primary completion	8 November 2017
Estimated completion	8 November 2017
Sites	33 locations across United States

Drugs / interventions tested

• Somatropin (Somatropin) — full drug profile →

Conditions studied

• Growth Hormone Deficiency — all drugs for Growth Hormone Deficiency →

Sponsor

Genentech, Inc. — full company profile →

Who can join

Adults 3 to 14, any sex, with Growth Hormone Deficiency. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Develop Anti-GH Antibodies After Treatment With Nutropin AQ v1.1 Primary · Baseline up to 1 year

Participants who were tested positive to anti-GH antibody after initiation of study treatment.

Group	Value	95% CI
Somatropin	3.7	0.77 – 10.44

Percentage of Participants Who Exhibit Functional Growth Attenuation Secondary · Baseline up to 1 year

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.

Group	Value	95% CI
Somatropin	2.6	0.31 – 8.96

Percentage of Participants With Neutralizing Antibodies Secondary · Baseline up to 1 year

Among participants who developed positive anti-GH antibody post-baseline, participants who were tested positive to neutralizing anti-GH antibody during study participation.

Group	Value	95% CI
Somatropin	0

Annualized Growth Velocity at Months 6 and 12 (Change From Baseline) Secondary · Months 6, 12

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).

6 months (Anti-GH Antibody Positive)

Group	Value	95% CI
Somatropin	5.3	± 2.89

6 months (Anti-GH Antibody Negative)

Group	Value	95% CI
Somatropin	5.5	± 2.64

12 months (Anti-GH Antibody Positive)

Group	Value	95% CI
Somatropin	5.2	± 3.61

12 months (Anti-GH Antibody Negative)

Group	Value	95% CI
Somatropin	4.9	± 2.40

Height Standard Deviation Score (SDS) at Months 6 and 12 (Change From Baseline) Secondary · Months 6, 12

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.

6 months (Anti-GH Antibody Positive)

Group	Value	95% CI
Somatropin	0.3	± 0.11

6 months (Anti-GH Antibody Negative)

Group	Value	95% CI
Somatropin	0.4	± 0.17

12 months (Anti-GH Antibody Positive)

Group	Value	95% CI
Somatropin	0.8	± 0.15

12 months (Anti-GH Antibody Negative)

Group	Value	95% CI
Somatropin	0.7	± 0.25

Percentage of Participants With Adverse Events Secondary · Baseline up to 1 year

Among participants who received at least one dose of study drug, those who reported at least one adverse event during study participation.

Group	Value	95% CI
Somatropin	69.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) were reported from Day 1 until 28 days after last dose of study medication for up to 12 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Somatropin

Serious: 0/82 (0%)

Deaths: 0/82

Other adverse events (8 terms — click to expand)

Reaction	System	Somatropin
Headache	Nervous system disorders	—
Vomiting	Gastrointestinal disorders	—
Upper respiratory tract infection	Infections and infestations	—
Injection site bruising	General disorders	—
Pharyngitis streptococcal	Infections and infestations	—
Rash	Skin and subcutaneous tissue disorders	—
Pyrexia	General disorders	—
Nasopharyngitis	Infections and infestations	—

Data from ClinicalTrials.gov NCT02311894 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Changes in Manufacturing Processes of Biologic Therapies Can Alter the Immunogenicity Profile of the Product.
   Vanderlaan M, Maniatis A, Olney R, Rahmaoui A, et al · · 2020 · cited 7× · PMID 31628764 · DOI 10.1002/cpt.1694