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Record W3159903976 · doi:10.1210/jendso/bvab048.1391

Phase 3 Study Evaluating Once Weekly Somatrogon Compared to Daily Genotropin in Japanese Patients With Pediatric Growth Hormone Deficiency (pGHD)

2021· article· en· W3159903976 on OpenAlexaff
Reiko Horikawa, Toshiaki Tanaka, Yukihiro Hasegawa, Tohru Yorifuji, David Ng, Ron G. Rosenfeld, Yuko Hoshino, Akifumi Okayama, Daisuke Shima, Roy Gomez, Aleksandra Pastrak, Orlando Castellanos

Bibliographic record

VenueJournal of the Endocrine Society · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSexual Differentiation and Disorders
Canadian institutionsOPKO Health (Canada)
Fundersnot available
KeywordsConfidence intervalMedicineClinical endpointHuman growth hormoneRandomized controlled trialAdverse effectGrowth hormone deficiencyInternal medicineHormoneGrowth hormonePediatrics

Abstract

fetched live from OpenAlex

Abstract Objectives: Somatrogon is a long-acting recombinant human growth hormone consisting of the amino acid sequence of human growth hormone and three copies of the carboxy-terminal peptide of human chorionic gonadotropin. Somatrogon is being developed as a once weekly treatment for children with pGHD. A Phase 3 trial was designed to compare the efficacy and safety of somatrogon administered once weekly with Genotropin administered once daily in Japanese patients with pGHD (ClinicalTrials. gov: NCT03874013). Methods: 44 Japanese pGHD patients (age 3-11 years) were randomized in a 1:1 ratio to receive either once weekly somatrogon (0.66 mg/kg/week) or once daily Genotropin (0.025 mg/kg/day) subcutaneously for 12 months. Somatrogon-treated patients had a pharmacokinetic assessment in the first 6 weeks with dose escalation occurring in 3 steps, at 0.25, 0.48, and 0.66 mg/kg/week, for 2 weeks at each dose. For the remaining 46 weeks, patients in the somatrogon treatment group continued to receive somatrogon at a dose of 0.66 mg/kg/week. The primary endpoint of the study was annualized height velocity (HV) at 12 months. Results: Baseline characteristics were balanced and comparable between the two treatment groups. The least square means of HV at month 12 were 9.65 cm/year in the somatrogon group (n=22) and 7.87 cm/year in the Genotropin group (n=22), with a point estimate treatment difference of 1.79 cm/year (95% confidence interval: 0.97, 2.60) in favour of somatrogon. The point estimate was greater than the pre-established mean treatment difference of -1.8 cm/year, which was the non-inferiority margin met in the global Phase 3 study (n=224) with somatrogon (0.66 mg/kg/week) and Genotropin (0.034mg/kg/day) (ClinicalTrials. gov: NCT02968004). Most of the adverse events were mild to moderate in severity and somatrogon was generally well-tolerated with no notable difference in safety between the two treatment groups. Injection site pain was more common in the somatrogon group (somatrogon: 72.7%, Genotropin: 13.6%). Conclusions: The Japanese Phase 3 trial in patients with pGHD demonstrated that once weekly somatrogon was comparable to daily Genotropin. The annual HV after 12 months of treatment was higher in the somatrogon group than the Genotropin group. Somatrogon administration was generally well tolerated in patients with pGHD. The results of this Japanese Phase 3 study are consistent with the results previously reported from the global Phase 3 study that met its primary endpoint of noninferiority to daily Genotropin.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.136
Threshold uncertainty score0.373

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.016
GPT teacher head0.304
Teacher spread0.288 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2021
Admission routes1
Has abstractyes

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