OBJECTIVES:The objective of this study is to investigate the safety, biodistribution, and exploratory clinical outcomes of enekinragene inzadenovec (PCRX-201), a high-capacity, nonintegrating, nonreplicating adenovirus serotype 5 vector expressing interleukin-1 receptor antagonist under the control of an inflammation-inducible promoter, in patients with moderate-to-severe knee osteoarthritis. METHODS:This open-label phase 1 trial (NCT04119687) enrolled participants aged 30 to 80 years with symptomatic (Western Ontario and McMaster Universities Osteoarthritis [WOMAC] pain score ≥ 5 and ≤ 9 [0-10-point scale]) and radiographic (Kellgren-Lawrence grade 2-4) knee osteoarthritis. In part 1, participants received a single intra-articular injection of PCRX-201 at 1 of 3 doses (n = 36). In part 2, participants received intra-articular methylprednisolone acetate immediately before PCRX-201 at the same dose (n = 36). Outcomes at week 104 included safety (primary endpoint), biodistribution (secondary endpoint), clinical outcomes (exploratory patient-reported endpoint), and immunogenicity. Data were analysed as observed. RESULTS:Transient treatment-related knee effusion was the most common adverse event and occurred less frequently in participants receiving glucocorticoid pretreatment (13/36 [36.1%]) than in those who did not (22/36 [61.1%]). Very limited biodistribution was detected outside the knee; only 2 participants had detectable PCRX-201 in plasma on days 1 and 4 postinjection. By week 104, 33/72 (45.8%) of participants had discontinued the study; however, those remaining showed sustained improvements with PCRX-201 for the exploratory outcomes of pain, stiffness, and function across doses and groups, regardless of preexisting neutralising antibody levels, with greater improvements observed in the glucocorticoid-pretreated group. CONCLUSIONS:A single intra-articular injection of PCRX-201 demonstrated safety and localised distribution within the knee. Exploratory patient-reported clinical outcomes suggest promise and support further investigation of PCRX-201.
Abstract Background/Aims The SELECT clinical program aims to evaluate the long-term integrated safety profile of upadacitinib 15mg (UPA15) across rheumatological indications, in the context of active comparators. Methods Safety data (cutoff: 15/08/2024) from 11 phase 3 upadacitinib clinical trials were compiled for RA (6), PsA (2), AS (2; one phase 2/3), and nr-axSpA (1) for this integrated analysis. Treatment-emergent adverse events (TEAEs)(adverse events [AEs] onset on/after the first dose of drug and ≤30 days [UPA15 and MTX] or ≤ 70 days [ADA] after the last dose) are presented as exposure-adjusted event rates (EAERs; events/100 patient-years [E/100 PY] with 95% CIs). A subset of special interest TEAEs are also presented as exposure-adjusted incidence rates (EAIRs; n/100 PY) with 95% CIs. Deaths (including COVID-19), MACE, VTE, and gastrointestinal perforations were adjudicated by blinded, independent committees. Results 4998 patients (RA, n = 3209; PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received UPA15(16,683.5 PYs of exposure), with >12,000 PYs of exposure from RA studies. The rate of AEs leading to drug discontinuation was generally similar across treatment groups and indications (range: 4.1 to 5.8 E/100 PY). The most frequently reported AEs leading to UPA15 discontinuation varied by indication; RA: pneumonia (n = 22/575; 0.2 E/100 PY), PsA: COVID-19 (n = 7/151; 0.2 E/100 PY), AS: headache (n = 3/42; 0.3 E/100 PY), nr-axSpA: worsening axial spondyloarthritis, pulmonary embolism, and nasal polyps (each n = 2/20; 0.5 E/100 PY), and pooled axSpA: headache and pulmonary embolism (each n = 4/62; 0.3 E/100 PY). Serious and opportunistic infection rates were generally similar across treatment groups and indications, except for serious infection in PsA (predominately COVID-19/COVID-19 pneumonia), which was higher with UPA15 than ADA. The most common serious infection and serious AE with UPA15 across all indications was COVID-19 pneumonia. Herpes zoster rates were higher with UPA15 versus active comparators in RA (ADA and MTX) and PsA (ADA). Herpes zoster rates with UPA15 were similar across indications. Rates of malignancy excluding nonmelanoma skin cancer (NMSC) were generally similar across treatment groups and indications. Rates of NMSC were generally low and were higher with UPA15 than active comparators in RA and PsA. MACE and VTE rates were generally similar across treatment groups and indications. Rates of extra-musculoskeletal manifestations were generally low across PsA, AS, nr-axSpA, and pooled axSpA. COVID-19/COVID-19 pneumonia was the most common cause of death across all indications. Conclusion Except for serious infection (in PsA, predominately COVID-19/COVID-19 pneumonia), herpes zoster, elevated CPK, and NMSC, reported TEAE rates were generally similar with UPA15 treatment and active comparators (ADA and MTX) in RA and PsA. As reported previously, across RA, PsA, AS, nr-axSpA, and pooled axSpA, UPA15 demonstrated a consistent safety profile, with no new safety risks identified with long-term treatment. Real-world data are needed to further contextualize and confirm findings. Disclosure G.R. Burmester: Consultancies; Has received speaking or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, MSD, Pfizer, Roche, and UCB. Honoraria; Has received speaking or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, MSD, Pfizer, Roche and UCB. S.B. Cohen: Consultancies; Has received consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Gilead, Pfizer, Roche, and Sandoz. Grants/research support; Has received research grants from AbbVie, Amgen, Boehringer Ingelheim, Gilead, Pfizer, Roche, and Sandoz. A. Deodhar: Consultancies; Has received consultancy fees from Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, Janssen and MoonLake. Honoraria; Has received speaker fees from Novartis and Pfizer. Grants/research support; Has received research grants from Novartis, Pfizer, AbbVie, Eli Lilly, and UCB Pharma. Other; Has received other support (medical writing support) from Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, Janssen and MoonLake. E. Mysler: Consultancies; Has received consultancy fees from AbbVie, Alpine Immunology, AstraZeneca, BMS, Eli Lilly, GSK, Hi Bio, Janssen, Novartis, Pfizer, Roche, and Sandoz. Grants/research support; Has received grants/research support from AbbVie, Alpine Immunology, AstraZeneca, BMS, Eli Lilly, GSK, Hi Bio, Janssen, Novartis, Pfizer, Roche, and Sandoz. A. Rubbert-Roth: Consultancies; Has received consultancy fees from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB. Honoraria; Has received honoraria for lectures from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB. Y. Tanaka: Honoraria; Has received speaking fees and/or honoraria from AbbVie, Asahi-Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, and YL Biologics. Grants/research support; Has received research grants from AbbVie, Asahi-Kasei, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, and Takeda. K.L. Winthrop: Consultancies; Has received consultancy fees from AbbVie, Bristol- Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, and UCB Pharma. Grants/research support; Has received research grants from AbbVie, Bristol- Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, and UCB Pharma. A. Gara: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. D. Coombs: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. I. Lagunes: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. L. Larbi: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. S. Meerwein: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. T. Shaw: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. C. Hansell: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. J. Curtis: Consultancies; Has received consultancy fees from AbbVie, Amgen, Bristol Myers Squibb, CorEvitas, Janssen, Labcorp, Lilly, Novartis, Pfizer, Sanofi/Regeneron, and UCB. Grants/research support; Has received research grants from AbbVie, Amgen, Bristol Myers Squibb, CorEvitas, Janssen, Labcorp, Lilly, Novartis, Pfizer, Sanofi/Regeneron, and UCB.
Aim: Scope of this work aims to explore the effectiveness of AI-powered outbound dialer campaigns with legacy outbound dialer campaigns by evaluating their technological capabilities, operational efficiencies, compliance features, customer experience impact, cost-effectiveness, and scalability. Study Design: This is a comparative analysis study evaluating two types of outbound dialer systems used in customer engagement campaigns. Place and Duration of Study: This study is based on a review of industry practices and integration strategies in contact centers across various organizations, focusing on solutions implemented between 2018 and 2024. Methodology: This study employed a comparative analysis methodology to evaluate AI-powered and legacy outbound dialer campaigns. The research was conducted through secondary data collection from industry reports, case studies, and real-world deployment insights over a study period spanning 2018 to 2024. Key performance metrics assessed included call connection rates, compliance adherence, personalization capabilities, operational costs, and scalability. Data was synthesized using a structured comparative framework to highlight technological, operational, and customer experience differences. Qualitative evaluations of agent productivity and customer satisfaction were also incorporated to provide a holistic analysis. Results: AI-powered outbound dialers demonstrated superior efficiency with call connection rates increasing by up to 30% compared to legacy systems. Automated regulatory monitoring strengthened compliance adherence, cutting violation risks by 40%. Personalization capabilities drove a 25% increase in customer satisfaction scores, while automation initiatives reduced operational costs by 20%. In contrast, legacy dialers faced higher abandonment rates and lacked real-time adaptability. Scalability and omnichannel integration were also more seamless in AI-powered systems, supporting modern customer engagement strategies. Conclusion: AI-powered outbound dialers outperform legacy systems in nearly all critical aspects, including efficiency, compliance, personalization, and cost-effectiveness. They provide a scalable, adaptive solution for businesses aiming to optimize customer engagement. While legacy systems may still be viable in smaller or less dynamic operations, AI-driven technologies are emerging as the preferred choice for future-proof outbound campaigns. Further adoption of AI-powered systems will continue to redefine industry standards.
