OR29-5 Phase 3 PaTHway Trial: Participants Treated With TransCon PTH Achieved Independence From Conventional Therapy While Maintaining Normal Serum Calcium
Notice bibliographique
Résumé
Abstract Background Adults with chronic hypoparathyroidism managed with conventional therapy (calcitriol, alfacalcidol, and oral calcium) generally report a reduced quality of life (QoL) and remain at risk for long-term complications from abnormal calcium and phosphate metabolism. The PaTHway trial assessed the efficacy and safety of TransCon PTH at Week 26. Methods PaTHway was a double-blind, placebo-controlled 26-week trial with 3: 1 randomization to TransCon PTH 18 mcg/d or placebo, co-administered with conventional therapy. The composite primary efficacy endpoint was the proportion of participants at Week 26 who achieved: serum calcium levels in the normal range (8.3–10.6 mg/dL), independence from conventional therapy defined as requiring no active vitamin D and ≤600 mg/day of calcium supplementation, and no increase in prescribed study drug over 4 weeks prior to Week 26. Key secondary endpoints included Hypoparathyroidism Patient Experience Scale (HPES) domain scores and 36-Item Short Form Survey (SF-36) subscale scores. Results 82 participants were dosed (78% female, mean age 49 years). 79 completed treatment through Week 26. 79% (48/61) of participants randomized to TransCon PTH met the composite primary efficacy endpoint, compared to 5% (1/21) in the placebo group (p <0.0001). 93% (57/61) participants treated with TransCon PTH achieved independence from conventional therapy. At baseline, mean serum calcium was 8.8 and 8.7 mg/dL for TransCon PTH and placebo respectively; 8.9 mg/dL and 8.2 mg/dL at Week 26, respectively. For TransCon PTH, mean urine calcium decreased significantly from 390 mg/24-hour at baseline to 220 mg/24-hour (normal range <250 mg/24-hour) at Week 26 compared to 329 mg/24-hour at baseline to 292 mg/24-hour at Week 26 for placebo. TransCon PTH therapy demonstrated a significant improvement in HPES-Symptom domain scores − Physical (p = 0.0038) and Cognitive (p = 0.0055), HPES-Impact domain scores − Physical Functioning (p = 0.0046) and Daily Life (p = 0.0061), and SF-36 Physical Functioning subscale score (p = 0.0347) compared to placebo. Overall, TransCon PTH was well-tolerated. The majority of adverse events (AE) were mild or moderate in severity. The most commonly reported study drug-related AEs were injection site reactions, hypercalcemia, and headaches. No study drug-related AEs led to withdrawal from the study. Conclusions In the PaTHway phase 3 trial, 79% of participants on TransCon PTH therapy (versus 5% on placebo) were able to achieve independence from conventional therapy while maintaining normocalcemia at Week 26. Uniquely, TransCon PTH therapy decreased and normalized 24-hour urine calcium excretion and significantly improved QoL (symptom burden and impact) from baseline compared to placebo. These data suggest the potential for TransCon PTH to improve clinical outcomes and QoL compared to current conventional therapy. Presentation: Tuesday, June 14, 2022 10:45 a.m. - 11:00 a.m.
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Comment cette classification a été obtenuedéplier
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 | 0,001 | 0,000 |
| 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 | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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.
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