Results From an Open-Label Extension of the Phase 2 Dose Finding Study of Once Weekly Somatrogon vs Daily Genotropin in Pediatric Patients With Growth Hormone Deficiency (GHD)
Notice bibliographique
Résumé
Abstract Background: Somatrogon, a long-acting recombinant human growth hormone, is being developed as a once weekly treatment for pediatric patients (pts) with GHD. A phase 2, 12 month study (NCT01592500) in pts with GHD showed that weekly somatrogon at 0.66 mg/kg/week had similar efficacy and safety to daily Genotropin. Pts who completed 12 months of treatment could be enrolled into an open-label extension (OLE). Aims: Evaluate the safety and efficacy of long-term exposure to somatrogon in pediatric pts with GHD who continued in the OLE for up to an additional 5 years. Methods: Methods for the main phase 2 study were published previously (Zelinska et al, 2017), in which 53 pts were randomized to 1 of 3 weekly somatrogon dose cohorts (0.25, 0.48, and 0.66 mg/kg/week) or the daily Genotropin cohort (0.24 mg/kg/week) for 12 months. After the main study (Periods I/II), 48 pts who consented to participate continued in the OLE, consisting of 3 periods: Period III=12 additional months at original somatrogon dose (Genotropin recipients randomized to 1 of the 3 somatrogon dose regimens); Period IV=subsequent years 2-4 with all pts receiving somatrogon at 0.66 mg/kg/week; Period V=ongoing, with pts transitioned from the vial to a pre-filled pen device at the same somatrogon dose (0.66 mg/kg/week). Data up to 1 year of Period V are reported. Results: Overall subject retention in different periods of this long-term study ranged from 87.5% to 97.7%. 39 pts (81.3%) reported at least one treatment-emergent adverse event (TEAE). Most TEAEs were mild or moderate in intensity and most were classified as unrelated to study treatment. 3 pts (6.3%) reported at least 1 serious adverse event (SAE); most SAEs were considered unrelated to study treatment, except for 1 instance of scoliosis. At the end of Period III, the mean annual height velocity (HV) was similar for the 0.25 and 0.48 mg/kg/week dose cohorts (7.73±1.89 and 7.54±1.28 cm/year, respectively) but was higher in the 0.66 mg/kg/week dose cohort (8.81±1.12 cm/year), consistent with the results of the main study. The HV at Periods IV and V showed sustained growth response. Height SDS showed consistent improvement and near normalization of height for age and gender after up to 6 years on somatrogon, irrespective of initial cohort assignment; height SDS at baseline of the main study was -3.98±1.22 and was well within the normal range at -0.69±0.87 at the end of Year 1 in Period V. IGF-1 SDS values remained above baseline and were maintained within the therapeutic target range with weekly somatrogon treatment at all time points in all OLE periods. Anti-drug antibodies (ADAs) were reported in 18 pts, of which 10 pts had ADAs in the main study. The presence of ADAs did not impact efficacy or safety. Conclusions: Somatrogon administered once weekly for up to 5 years after the main study was generally well tolerated and participants showed sustained improvement in annual HV, height SDS, and delta height SDS.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
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 tête enseignante, 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 ».