دورية أكاديمية
Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design.
| العنوان: | Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design. |
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| المؤلفون: | Groarke JD; Internal Medicine Research Unit, Pfizer Inc, Cambridge, MA, USA., Crawford J; Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA., Collins SM; Global Biometrics and Data Management, Pfizer R&D UK Ltd, Sandwich, Kent, UK., Lubaczewski SL; Early Clinical Development and Biomedicine Artificial Intelligence, Pfizer Inc, Collegeville, PA, USA., Breen DM; Internal Medicine Research Unit, Pfizer Inc, Cambridge, MA, USA., Harrington MA; Global Access and Value, Pfizer Inc, Cambridge, MA, USA., Jacobs I; Global Product Development, Pfizer Inc, New York, NY, USA., Qiu R; Clinical Pharmacology, Pfizer Inc, Cambridge, MA, USA., Revkin J; Internal Medicine Research Unit, Pfizer Inc, Cambridge, MA, USA., Rossulek MI; Internal Medicine Research Unit, Pfizer Inc, Cambridge, MA, USA., Saxena AR; Internal Medicine Research Unit, Pfizer Inc, Cambridge, MA, USA. |
| المصدر: | Journal of cachexia, sarcopenia and muscle [J Cachexia Sarcopenia Muscle] 2024 Jun; Vol. 15 (3), pp. 1054-1061. Date of Electronic Publication: 2024 Mar 18. |
| نوع المنشور: | Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders Country of Publication: Germany NLM ID: 101552883 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2190-6009 (Electronic) Linking ISSN: 21905991 NLM ISO Abbreviation: J Cachexia Sarcopenia Muscle Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2015- : Berlin : John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders Original Publication: Heidelburg : Springer-Verlag |
| مواضيع طبية MeSH: | Cachexia*/etiology , Cachexia*/drug therapy , Neoplasms*/complications, Adult ; Female ; Humans ; Male ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antibodies, Monoclonal, Humanized/pharmacology ; Growth Differentiation Factor 15/blood |
| مستخلص: | Background: Cancer cachexia is a multifactorial metabolic wasting syndrome characterized by anorexia, unintentional loss of weight involving both skeletal muscle and adipose tissues, progressive functional impairment and reduced survival. Therapeutic strategies for this serious condition are very limited. Growth differentiation factor 15 (GDF-15) is a cytokine that is implicated in cancer cachexia and may represent both a biomarker of cancer cachexia and a potential therapeutic target. Ponsegromab is a potent and selective humanized monoclonal antibody that inhibits GDF-15-mediated signalling. Preclinical and preliminary phase 1 data suggest that ponsegromab-mediated inactivation of circulating GDF-15 may lead to improvement in key characteristics of cachexia. The primary objective of this phase 2 study is to assess the effect of ponsegromab on body weight in patients with cancer, cachexia and elevated GDF-15 concentrations. Secondary objectives include assessing physical activity, physical function, actigraphy, appetite, nausea and vomiting, fatigue and safety. Exploratory objectives include evaluating pharmacokinetics, pharmacodynamics, immunogenicity, lumbar skeletal muscle index and Response Evaluation Criteria in Solid Tumors. Methods: Approximately 168 adults with non-small-cell lung, pancreatic or colorectal cancers who have cachexia and elevated GDF-15 concentrations will be randomized in a double-blind, placebo-controlled study (NCT05546476). Participants meeting eligibility criteria will be randomized 1:1:1:1 to one of three dose groups of ponsegromab (100, 200 or 400 mg) or matching placebo administered subcutaneously every 4 weeks for an initial 12-week treatment period. This is followed by optional open-label treatment with ponsegromab of 400 mg administered every 4 weeks for up to 1 year. The primary endpoint is mean change from baseline in body weight at Week 12. A mixed model for repeated measures followed by a Bayesian E Perspective: Cancer-related cachexia is an area of significant unmet medical need. This study will support the clinical development of ponsegromab as a novel inhibitor of GDF-15, which may ameliorate key pathologies of cancer cachexia to improve patient symptoms, functionality and quality of life. Trial Registration: ClinicalTrials.gov ID: NCT05546476. (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.) |
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| معلومات مُعتمدة: | Pfizer |
| فهرسة مساهمة: | Keywords: GDF‐15; cachexia; cancer; ponsegromab; weight loss |
| سلسلة جزيئية: | ClinicalTrials.gov NCT05546476 |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal, Humanized) 0 (Growth Differentiation Factor 15) |
| تواريخ الأحداث: | Date Created: 20240319 Date Completed: 20240606 Latest Revision: 20240820 |
| رمز التحديث: | 20240820 |
| مُعرف محوري في PubMed: | PMC11154777 |
| DOI: | 10.1002/jcsm.13435 |
| PMID: | 38500292 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2190-6009 |
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| DOI: | 10.1002/jcsm.13435 |