scholarly journals Correction to: Safety and efficacy of azilsartan in paediatric patients with hypertension: a phase 3, single-arm, open-label, prospective study

2022 ◽  
Author(s):  
Shuichi Ito ◽  
Yuya Nishiyama ◽  
Kenkichi Sugiura ◽  
Kazuaki Enya
Keyword(s):  
Prospective Study ◽  
Open Label ◽  
Phase 3 ◽  
Safety And Efficacy ◽  
Paediatric Patients

Safety and Efficacy of Elotuzumab with Lenalidomide/Dexamethasone for Multiple Myeloma in a Japanese Subpopulation Analysis of the Phase 3 Eloquent-2 Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3315-3315
Author(s):  
Kazuteru Ohashi ◽  
Kenshi Suzuki ◽  
Kazutaka Sunami ◽  
Shinsuke Iida ◽  
Shinichiro Okamoto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Nk Cells ◽  
Research Funding ◽  
Pharmaceutical Research ◽  
Incidence Rates ◽  
Open Label ◽  
Phase 3 ◽  
Safety And Efficacy ◽  
Infusion Reactions ◽  
Adjusted Incidence

Abstract Background: Elotuzumab is an immunostimulatory monoclonal antibody that binds to signaling lymphocytic activation molecule family member 7 (SLAMF7), which is expressed on myeloma and natural killer (NK) cells. Elotuzumab has a dual mode of action: directly activating NK cells and tagging myeloma cells, thereby initiating antibody-dependent cell-mediated cytotoxicity. In the phase 3 ELOQUENT-2 (NCT01239797) trial involving patients (pts) with relapsed/refractory multiple myeloma (RRMM), elotuzumab in combination with lenalidomide/dexamethasone (ELd) was compared with lenalidomide/dexamethasone alone (Ld) and demonstrated improved progression-free survival (PFS; hazard ratio [HR] 0.70, p<0.001) and overall response rate (ORR; 79% vs 66%, p<0.001) (Lonial S et al. N Engl J Med 2015;373:621-31). We assessed the safety and efficacy of elotuzumab in the ELOQUENT-2 Japanese subpopulation. Methods: ELOQUENT-2 was a phase 3, open-label, multicenter trial that enrolled pts with RRMM and 1-3 prior therapies. Pts were randomized 1:1 to elotuzumab (10 mg/kg) plus Ld or Ld in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. All pts received premedication before elotuzumab administration to mitigate infusion reactions. Coprimary endpoints were PFS and ORR. Secondary endpoints and exploratory objectives included overall survival (OS) and safety, respectively. Results: ELOQUENT-2 included 60 Japanese pts in the all-randomized population of 646: 31/321 ELd and 29/325 Ld. The median age was 69 years (range 45-80) in the ELd group and 66 years (range 47-84) in the Ld group. Forty percent (24/60) of pts were refractory to their most recent line of therapy. The median duration of therapy was 22 cycles (range 2-38) in ELd group and 16 cycles (range 3-36) in the Ld group. The data cut-off excluding OS was October 2014; OS was updated October 2015. PFS (ELd vs Ld) was 74% (95% confidence interval [CI]: 55-86) vs 66% (95% CI: 45-80) at 1 year, and 48% (95% CI: 29-65) vs 18% (95% CI: 7-34) at 2 years (Figure). HR for PFS (ELd vs Ld) was 0.51 (95% CI: 0.3-1.1), a 49% reduction in risk of progression/death. Median PFS was 22.2 months (95% CI: 17.5-not estimated [NE]) in the ELd group and 18.5 months (95% CI: 11.1-21.2) in the Ld group. ORR was similar in both groups: 84% (95% CI: 66-95) in the ELd group vs 86% (95% CI: 68-96) in the Ld group. The interim HR for OS between the ELd and Ld groups was 0.81 (95% CI: 0.35-1.87). Survival rates in ELd and Ld pts, respectively, at 1 year were 100% (95% CI: NE-NE) and 97% (95% CI: 78-100); at 2 years, 90% (95% CI: 73-97) and 86% (95% CI 67-94); and at 3 years, 68% (95% CI: 48-81) and 64% (95% CI: 44-79). Grade 3/4 adverse events (AEs) occurring in ≥10% in either groups were neutropenia (ELd 26%, Ld 31%), cataract (ELd 19%, Ld 14%), pneumonia (ELd 19%, Ld 3%), lymphocytopenia (ELd 19%, Ld 3%), decreased appetite (ELd 7%, Ld 14%), anemia (ELd 7%, Ld 10%), hyperglycemia (ELd 7%, Ld 10%), and thrombocytopenia (ELd 3%, Ld 14%). Infections were reported in 81% (25/31) and 79% (23/29) in the ELd and Ld groups, respectively, with exposure-adjusted incidence rates of infection (per 100 person-years) of 172.6 and 183.4, respectively. The incidence of pneumonia was 29% (9/31) vs 7% (2/29) in the ELd and Ld groups, respectively, with exposure-adjusted incidence rates of infection (per 100 person-years) of 16.7 and 4.5, respectively. All pneumonia AEs were reported as serious AEs and were resolved by elotuzumab omission or treatment with antibiotics. No pts discontinued elotuzumab due to pneumonia. Infusion reactions were observed in 4 pts (13%) in the ELd group; all were Grade 1. Conclusions: In the Japanese ELOQUENT-2 population, elotuzumab showed durable efficacy, with improved PFS and ORR, and with acceptable safety. Incidence of pneumonia tended to be higher with ELd vs Ld in the Japanese subanalysis. All cases were manageable, and none led to treatment discontinuation. Within the constraints of a small subgroup, results were consistent between Japanese pts and the overall pt population. Study support: Bristol-Myers Squib, Princeton, New Jersey, USA Disclosures Sunami: Ono Pharmaceutical: Research Funding; Daiichi Sankyo: Research Funding; Bristol-Myers Squibb K.K.: Research Funding; Novartis: Research Funding; Celgene: Honoraria, Research Funding; Takeda: Research Funding; Sanofi: Research Funding; Janssen Pharmaceutical: Research Funding. Iida:Celgene: Honoraria, Research Funding; Janssen Pharmaceuticals: Honoraria, Research Funding. Okamoto:Nippon Shinyaku Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Asahi Kasei Pharma Corp.: Research Funding; Alexion Pharmaceuticals, Inc.: Research Funding; Bristol-Myers Squibb K.K.: Honoraria, Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Teijin Pharma Limited: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Toyama Chemical Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Shionogi & Co., Ltd.: Research Funding; Pfizer Inc.: Honoraria, Research Funding; JCR Pharmaceuticals Co., Ltd.: Research Funding. Miyoshi:Bristol-Myers Squibb K.K.: Employment. Bleickardt:Bristol-Myers Squibb: Employment. Matsumoto:Celgene: Honoraria; Janssen Pharmaceutical: Honoraria.

scholarly journals Tamoxifen in Duchenne muscular dystrophy (TAMDMD): study protocol for a multicenter, randomized, placebo-controlled, double-blind phase 3 trial

2019 ◽  
Author(s):  
Sara Nagy ◽  
Patricia Hafner ◽  
Simone Schmidt ◽  
Daniela Rubino-Nacht ◽  
Sabine Schädelin ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Motor Function ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Open Label Extension ◽  
To Receive ◽  
Function Measure

Abstract BACKGROUND Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder of childhood with a devastating disease course. Several targeted gene therapies and molecular approaches have been or are currently tested in clinical trials; however, a causative therapy is still not available and best supportive care is limited to oral glucocorticoids with numerous long-term side effects. Tamoxifen is a selective estrogen receptor regulator, and shows besides its antitumor activity also antioxidant actions and regulatory roles in the calcium homeostasis. In a mouse model of DMD, oral tamoxifen significantly improved muscle strength and reduced muscle fatigue. This multicenter, randomized, double-blind, placebo controlled phase 3 trial aims to demonstrate safety and efficacy of tamoxifen over placebo in pediatric patients with DMD. After completion of the double-blind phase, an open label extension of the study will be offered to all participants. METHODS/DESIGN At least 71 ambulant and up to 20 non-ambulant patients with DMD are planned to be enrolled at multiple European sites. Patients will be randomly assigned to receive either tamoxifen 20mg or placebo daily over 48 weeks. In the open-label extension phase, all patients will be offered to receive tamoxifen for further 48 weeks. The primary endpoint of the double-blind phase is defined as the change of the D1 domain of the motor function measure in ambulant patients or a change of the D2 domain in non-ambulant patients under tamoxifen compared to placebo. Secondary outcome measures include change in timed function tests, quantitative muscle testing, and quantitative MRI of thigh muscles. Laboratory analyses including biomarkers of tamoxifen metabolism and muscle dystrophy will also be assessed. DISCUSSION The aim of the study is to investigate whether tamoxifen can reduce disease progression in ambulant and non-ambulant DMD patients over 48 weeks. Motor function measure comprises the primary endpoint, whereas further clinical and radiological assessments and laboratory biomarkers are performed to provide more data on safety and efficacy. An adjacent open label extension phase is planned to test if earlier initiation of the treatment with tamoxifen (verum arm of double blind phase) compared to a delayed start can reduce disease progression more efficiently.

scholarly journals Cell-free stem cell-derived extract formulation for treatment of knee osteoarthritis: study protocol for a preliminary non-randomized, open-label, multi-center feasibility and safety study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ashim Gupta ◽  
Nicola Maffulli ◽  
Hugo C. Rodriguez ◽  
R. Justin Mistovich ◽  
Kristin Delfino ◽  
...  
Keyword(s):  
Stem Cell ◽  
Magnetic Resonance ◽  
Prospective Study ◽  
Open Label ◽  
Safety And Efficacy ◽  
Knee Oa ◽  
Symptomatic Knee ◽  
Essential Components ◽  
Patient Reported ◽  
Grade Ii

Abstract Background Musculoskeletal conditions are highly prevalent, and knee OA is most common. Current treatment modalities have limitations and either fail to solve the underlying pathophysiology or are highly invasive. To address these limitations, attention has focused on the use of biologics. The efficacy of these devices is attributed to presence of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs). With this in mind, we formulated a novel cell-free stem cell-derived extract (CCM) from human progenitor endothelial stem cells (hPESCs). A preliminary study demonstrated the presence of essential components of regenerative medicine, namely GFs, CKs, and EVs, including exosomes, in CCM. The proposed study aims to evaluate the safety and efficacy of intraarticular injection of the novel cell-free stem cell-derived extract (CCM) for the treatment of knee OA. Methods and analysis This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular CCM in patients suffering from grade II/III knee OA will be evaluated. Up to 20 patients with grade II/III OA who meet the inclusion and exclusion criteria will be consented and screened to recruit 12 patients to receive treatment. The study will be conducted at up to 2 sites within the USA, and the 12 participants will be followed for 24 months. The study participants will be monitored for adverse reactions and assessed using Numeric Pain Rating Scale (NPRS), Patient-Reported Outcomes Measurement Information System (PROMIS) Score, Knee Injury and Osteoarthritis Outcome Score Jr. (KOOS Jr.), 36-ietm short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and magnetic resonance imaging (MRI) with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, function, satisfaction, and cartilage regeneration. Discussion This prospective study will provide valuable information into the safety and efficacy of intraarticular administration of cell-free stem cell-derived extract (CCM) in patients suffering with grade II/III knee OA. The outcomes from this initial study of novel CCM will lay the foundation for a larger randomized, placebo-controlled, multi-center clinical trial of intraarticular CCM for symptomatic knee OA. Trial registration Registered on July 21, 2021. ClinicalTrials.gov NCT04971798

scholarly journals Tamoxifen in Duchenne muscular dystrophy (TAMDMD): study protocol for a multicenter, randomized, placebo-controlled, double-blind phase 3 trial

2019 ◽  
Author(s):  
Sara Nagy ◽  
Patricia Hafner ◽  
Simone Schmidt ◽  
Daniela Rubino-Nacht ◽  
Sabine Schädelin ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Motor Function ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Open Label Extension ◽  
To Receive ◽  
Function Measure

Abstract BACKGROUND Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder of childhood with a devastating disease course. Several targeted gene therapies and molecular approaches have been or are currently tested in clinical trials; however, a causative therapy is still not available and best supportive care is limited to oral glucocorticoids with numerous long-term side effects. Tamoxifen is a selective estrogen receptor regulator, and shows besides its antitumor activity also antioxidant actions and regulatory roles in the calcium homeostasis. In a mouse model of DMD, oral tamoxifen significantly improved muscle strength and reduced muscle fatigue. This multicenter, randomized, double-blind, placebo controlled phase 3 trial aims to demonstrate safety and efficacy of tamoxifen over placebo in pediatric patients with DMD. After completion of the double-blind phase, an open label extension of the study will be offered to all participants. METHODS/DESIGN At least 71 ambulant and up to 20 non-ambulant patients with DMD are planned to be enrolled at multiple European sites. Patients will be randomly assigned to receive either tamoxifen 20mg or placebo daily over 48 weeks. In the open-label extension phase, all patients will be offered to receive tamoxifen for further 48 weeks. The primary endpoint of the double-blind phase is defined as the change of the D1 domain of the motor function measure in ambulant patients or a change of the D2 domain in non-ambulant patients under tamoxifen compared to placebo. Secondary outcome measures include change in timed function tests, quantitative muscle testing, and quantitative MRI of thigh muscles. Laboratory analyses including biomarkers of tamoxifen metabolism and muscle dystrophy will also be assessed. DISCUSSION The aim of the study is to investigate whether tamoxifen can reduce disease progression in ambulant and non-ambulant DMD patients over 48 weeks. Motor function measure comprises the primary endpoint, whereas further clinical and radiological assessments and laboratory biomarkers are performed to provide more data on safety and efficacy. An adjacent open label extension phase is planned to test if earlier initiation of the treatment with tamoxifen (verum arm of double blind phase) compared to a delayed start can reduce disease progression more efficiently.

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