OR21-04 Long-term Efficacy And Safety Of Once-weekly Somatrogon In Pediatric Subjects With Growth Hormone Deficiency: Results From Up To 8 Years Of Somatrogon Treatment
Notice bibliographique
Résumé
Abstract Disclosure: Z. Zadik: None. N. Zelinska: Consulting Fee; Self; Novo Nordisk, Berlin-Chemie, Medtronic, Sanofi-Aventis. Research Investigator; Self; MacroGenics, Novo Nordisk, Pfizer, Inc., Merck, OPKO Health, Ferring Pharmaceuticals, Teva Pharmaceutical Industries Ltd., Parexel, Genexine. Speaker; Self; Medtronic, Berlin-Chemie, ACINO, Novo Nordisk, Pfizer, Inc., Sanofi-Aventis, Johnson &Johnson, Wörwag Pharma. V. Iotova: Grant Recipient; Self; Pfizer, Inc. Speaker; Self; Novo Nordisk, Pfizer, Inc., Swixx, Sandoz, Berlin-Chemie. Y. Skorodok: None. O.A. Malievskiy: None. N. Mauras: Consulting Fee; Self; Agios. Grant Recipient; Self; Novo Nordisk, Abbvie. Research Investigator; Self; OPKO Health, Abbvie, Beta Bionics. S.R. Valluri: Employee; Self; Pfizer, Inc. Stock Owner; Self; Pfizer, Inc. A. Pastrak: Employee; Self; OPKO Health. Stock Owner; Self; OPKO Health. R.G. Rosenfeld: Advisory Board Member; Self; Lumos, DNARx, BioMarin. Consulting Fee; Self; OPKO Health. C.T. Taylor: Employee; Self; Pfizer, Inc. Stock Owner; Self; Pfizer, Inc. M. Nijher: Employee; Self; Pfizer, Inc. Stock Owner; Self; Pfizer, Inc. C. Roland: Employee; Self; Pfizer, Inc. Stock Owner; Self; Pfizer, Inc. R. Wang: Employee; Self; Pfizer, Inc. Stock Owner; Self; Pfizer, Inc. M.P. Wajnrajch: Employee; Self; Pfizer, Inc. Stock Owner; Self; Pfizer, Inc. J.F. Cara: Employee; Self; Pfizer, Inc. Stock Owner; Self; Pfizer, Inc. Introduction: Somatrogon, a long-acting recombinant human growth hormone, is approved in multiple countries as a once-weekly treatment for pediatric growth hormone deficiency (pGHD). This abstract describes results from up to 8 y of study (main study + open label extension [OLE]) evaluating the efficacy and safety of somatrogon in pGHD. Methods: This randomized, open-label, dose-finding Phase 2 study comprised 5 treatment periods. Subjects were randomized 1:1:1:1 to once-weekly somatrogon (titrated up to 0.25, 0.48, or 0.66 mg/kg/wk) or once-daily Genotropin (0.24 mg/kg/wk) for 12 mo of the main study (periods I and II), after which they were eligible to enroll in the OLE (periods III-V). In period III, somatrogon recipients continued at their previous dose; Genotropin recipients were re-randomized to 1 of the 3 somatrogon doses. In period IV (OLE Year (Y)2–4), all subjects switched to somatrogon 0.66mg/kg/wk; in period V (OLE Y5 onward), all subjects switched from single-use somatrogon vials to prefilled pen devices (somatrogon 0.66 mg/kg/wk). Results: Of 53 subjects who completed the main study, 48 entered the OLE. At OLE entry, 66.7% were male, all but 1 were pubertal Tanner stage 1, and mean (SD) age was 7.7 (2.1) y. At OLE Y6 end, there were 30 subjects with a mean±SD height velocity (HV) of 6.47±2.07 cm/y and a mean±SD height SD score (HT SDS) of 0.43±0.94. At OLE Y7 end, 26 subjects had a mean±SD HV of 5.31±1.68 cm/y and a mean HT SDS of 0.44±0.96. Four subjects achieved final height (defined as HV <1 cm/y). Their HVs in the last 6-mo interval and last assessed heights were: subject 1: 0.54 cm/y, 174.5 cm; subject 2: 0.7 cm/y, 173.2 cm; subject 3: 0.56 cm/y, 179.5 cm; and subject 4: 0.19 cm/y, 168.7 cm. Somatrogon efficacy was not affected by positive test results for antidrug antibodies (ADA). HV and cumulative ΔHT SDS (cΔHT SDS) were similar between subjects who tested ADA+ vs ADA-: at OLE Y6 end, 15 who tested ADA+ had HV 6.47±1.69 cm/y and cΔHT SDS 3.09±1.04; and 15 who tested ADA- had HV 6.48±2.46 cm/y and cΔHT SDS 3.62±1.40. At OLE Y7 end, 14 subjects who tested ADA+ had HV 5.22±1.52 cm/y and cΔHT SDS 3.06±0.98; 12 who tested ADA- had HV 5.42±1.91 cm/y and cΔHT SDS 3.75±1.39. In OLE Y7, TEAEs were reported in 35.5% subjects, which was lower than the main study (69.0%) and OLE Y1–6 (range: 41.9–57.5%). No serious TEAEs or TEAEs leading to study drug withdrawal occurred in OLE Y7. Study drug–related TEAEs occurred in 2 subjects: keeled chest acquired and scoliosis in 1 and arthralgia in 1. No deaths were reported throughout the OLE. Conclusion: Following up to 8 y of somatrogon treatment, including 7 y of the OLE, subjects demonstrated continued growth, 4 achieved final height, and somatrogon maintained a favorable safety profile. Testing ADA+ did not appear to affect subject growth. Clinicaltrials.gov: NCT01592500. Acknowledgements: The authors wish to thank all the investigators involved in this study. Presentation: Saturday, June 17, 2023
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».