scholarly journals 97. Tetravalent Dengue Vaccine (TAK-003) Development Program: A Bird’s Eye View

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S61-S61
Author(s):  
Vianney Tricou ◽  
Shibadas Biswal ◽  
Mengya Liu ◽  
Sanjay S Patel ◽  
Olaf Zent ◽  
...  
Keyword(s):  
Development Program ◽  
Hemorrhagic Fever ◽  
Viral Disease ◽  
Vaccination Schedule ◽  
Phase Iii ◽  
Effective Vaccine ◽  
Healthy Children ◽  
Dengue Vaccine ◽  
Pivotal Phase ◽  
Phase Iii Study

Abstract Background Dengue fever is a mosquito-borne viral disease endemic in 128 countries. An unmet clinical need remains for an effective vaccine that can be used more broadly than the vaccine presently available. A clinical development program has evaluated the long-term safety, immunogenicity, and vaccine efficacy (VE) of TAK-003, a live attenuated tetravalent dengue vaccine with a DENV-2 backbone engineered to elicit immune responses to all 4 dengue serotypes. Methods 18 clinical trials in 13 countries have involved 28,175 seropositive/seronegative participants aged from 1.5-60 years from endemic/non-endemic regions. In the ongoing pivotal phase III study, 4–16-year-old healthy children (N=20,099) were randomized 2:1 to receive two doses of TAK-003 or placebo, 3 months apart for an evaluation of VE and safety over a multi-year period stratified pre-vaccination dengue serostatus. Active surveillance throughout the trial detected symptomatic dengue. The trial will continue up to 4–4.5 years post 2nd dose, and for another 25 months after a booster dose. Data up to 3 years after the second vaccination are currently available. Results Safety and immunogenicity data from Phase I/II studies established the final formulation and dosing schedule. Overall VE in the pivotal phase III study was 80.2% [95% CI: 73.3–85.3] against virologically confirmed dengue (VCD) at 12 months post 2nd dose. At 18 months, VE was 66.2% (95% CI: 49.1–77.5) in dengue-naive and 76.1% (95% CI: 68.5–81.9) in dengue pre-exposed participants, with VE of 90.4% (95% CI: 82.6–94.7) and 85.9% (95% CI: 31.9–97.1) for prevention of hospitalized VCD and dengue hemorrhagic fever, respectively. Cumulative VE against VCD from first dose to 3 years post 2nd dose was 62.0% (95% CI: 56.6–66.7) and 83.6% (95% CI: 76.8–88.4) in prevention of hospitalized VCD. Some decline in VE was observed over time mainly driven by outpatient dengue. Two doses of TAK-003 3 months apart were well-tolerated with no important safety risks identified up to 3 years after completion of the vaccination schedule. Conclusion TAK-003 is immunogenic against all 4 dengue serotypes and continues to be efficacious, well-tolerated, and with no evidence of disease enhancement in seronegative population up to 3 years post-vaccination. Disclosures Vianney Tricou, D Phil, Takeda Pharmaceuticals International (Employee) Shibadas Biswal, MD, Takeda Vaccines, Inc (Employee) Sanjay S. Patel, PhD, Takeda Pharmaceuticals International AG (Employee) Olaf Zent, MD, Takeda Pharmaceuticals International AG (Employee) Martina Rauscher, PhD, Takeda Pharmaceuticals International AG (Employee) Gonzalo Perez, MD, Takeda group companies (Employee) Walid Kandeil, MD, Takeda Pharmaceuticals International AG (Employee) Nicolas Folschweiller, PhD, Takeda (Employee)

scholarly journals Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2–11 years in Malaysia: A randomized, placebo-controlled, Phase III study

Vaccine ◽  
2013 ◽  
Vol 31 (49) ◽  
pp. 5814-5821 ◽  
Author(s):  
Amar-Singh HSS ◽  
Mia-Tuang Koh ◽  
Kah Kee Tan ◽  
Lee Gaik Chan ◽  
Lynn Zhou ◽  
...  
Keyword(s):  
Phase Iii ◽  
Healthy Children ◽  
Dengue Vaccine ◽  
Phase Iii Study

scholarly journals Genetic epidemiology of dengue viruses in phase III trials of the CYD tetravalent dengue vaccine and implications for efficacy

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Maia A Rabaa ◽  
Yves Girerd-Chambaz ◽  
Kien Duong Thi Hue ◽  
Trung Vu Tuan ◽  
Bridget Wills ◽  
...  
Keyword(s):  
Genetic Epidemiology ◽  
Phase Iii ◽  
Envelope Gene ◽  
Dengue Vaccine ◽  
Virus Genotype ◽  
Pivotal Phase ◽  
Dengue Viruses ◽  
High Amino Acid ◽  
Phase Iii Trials ◽  
Trial Participants

This study defined the genetic epidemiology of dengue viruses (DENV) in two pivotal phase III trials of the tetravalent dengue vaccine, CYD-TDV, and thereby enabled virus genotype-specific estimates of vaccine efficacy (VE). Envelope gene sequences (n = 661) from 11 DENV genotypes in 10 endemic countries provided a contemporaneous global snapshot of DENV population genetics and revealed high amino acid identity between the E genes of vaccine strains and wild-type viruses from trial participants, including at epitope sites targeted by virus neutralising human monoclonal antibodies. Post-hoc analysis of all CYD14/15 trial participants revealed a statistically significant genotype-level VE association within DENV-4, where efficacy was lowest against genotype I. In subgroup analysis of trial participants age 9–16 years, VE estimates appeared more balanced within each serotype, suggesting that genotype-level heterogeneity may be limited in older children. Post-licensure surveillance is needed to monitor vaccine performance against the backdrop of DENV sequence diversity and evolution.

BIOBOARD

2015 ◽  
Vol 19 (07) ◽  
pp. 28-37
Keyword(s):  
United States ◽  
Progressive Multiple Sclerosis ◽  
Phase Iii ◽  
Pivotal Phase ◽  
Non Invasive ◽  
Prenatal Diagnostic ◽  
Test Version ◽  
Diagnostic Technology ◽  
Phase Iii Study ◽  
Technology Upgrade

AUSTRALASIA – Mighty River Honey: Saving the Bee Through Social Enterprise SINGAPORE – A*STAR’S IME AND INEX Innovations Exchange to Develop Non-invasive Prenatal Diagnostic Technology SINGAPORE – CellResearch Corporation receives new US patent approval for exclusive stem cell technology amidst new partnerships SINGAPORE – A Gel That Can Make Drugs Last Longer JAPAN – Japanese Biotech JCR Pharmaceuticals Selects Medidata’s Cloud-Based Platform to Power Rare Disease Clinical Research in Japan PARIS – MedDay Reports Additional Positive Data of its Pivotal Phase III Study With MD1003 in Patients with Progressive Multiple Sclerosis GERMANY – Merck Serono Introduces New Eeva Test Version Aiming for Optimized Assisted Reproductive Outcomes AFRICA – Ebola Genome Insights Indicate that Containment Worked UNITED STATES – TissueGene, Inc. Announces FDA Acceptance Of Invossa™ As Proprietary Name For TissueGene-C UNITED STATES – FDA Approves Technology Upgrade for Recipients of First Commercially Available Cochlear Implant

A randomized, multicenter, open-label, phase III study of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765) versus ofatumumab in patients (pts) with relapsed or refractory (RR) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): RESONATE.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS8619-TPS8619
Author(s):  
John C. Byrd ◽  
Jacqueline Claudia Barrientos ◽  
Stephen Devereux ◽  
Jennifer R. Brown ◽  
Neil E. Kay ◽  
...  
Keyword(s):  
Package Insert ◽  
Cell Receptor ◽  
Primary Objective ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Controlled Study ◽  
Open Label ◽  
Pivotal Phase ◽  
Phase Iii Study ◽  
Line Of Therapy

TPS8619 Background: Chemoimmunotherapy (CIT) treatment approaches such as FCR have markedly improved outcomes for CLL pts when administered as initial or second-line therapy. Despite this progress, virtually all pts relapse and effective salvage regimens that induce durable remissions or can be administered safely to elderly pts or those with comorbidities are lacking. BTK, an essential mediator of B-cell receptor signaling, is a novel target in CLL. Ibrutinib, a first-in class inhibitor of BTK, promotes apoptosis and inhibits proliferation, migration and adhesion in CLL cells. Phase II data of ibrutinib monotherapy in RR CLL demonstrated an estimated PFS and OS of 75% and 83% respectively at 26 months (Byrd Abst #189 ASH 2012). These findings confirmed BTK as an important target in CLL and supported initiation of a pivotal phase III study in pts with RR CLL/SLL. Methods: PCYC-1112-CA is an ongoing international Phase 3 randomized controlled study of ibrutinib versus ofatumumab for treatment of pts with RR CLL/SLL. The study is enrolling 350 planned pts in 9 countries. Pts are randomized 1:1 to receive ibrutinib 420 mg orally once daily or ofatumumab per the package insert at 300 mg for the first dose, then 2000 mg for a total of 12 doses over 24 weeks. Pts are stratified based on del 17p and disease refractory to purine analogs. Key inclusion criteria include RR CLL/SLL with >= 1 prior line of therapy including pts who experienced a short remission duration to purine analog based CIT, pts who are older or have comorbidities, and pts with del 17p. Pts must have active disease meeting criterion for requiring therapy and measurable nodal disease by CT. Key exclusion criteria include Richter’s transformation, stem cell transplantation within 6 months, GVHD or immunosuppression, platelet count <30,000 cells/ul or use of warfarin The primary objective of the study is PFS evaluated by an IRC. Other outcomes include ORR, OS, hematologic improvement, and safety. An independent DMC is monitoring the study. Clinical trial information: NCT01744691.

The efficacy and safety of sunitinib in patients with advanced well-differentiated pancreatic neuroendocrine tumors.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 380-380 ◽  
Author(s):  
Eric Raymond ◽  
Matthew H. Kulke ◽  
Shukui Qin ◽  
Michael Schenker ◽  
Antonio Cubillo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neuroendocrine Tumors ◽  
Phase Iii ◽  
Pancreatic Neuroendocrine Tumors ◽  
Pivotal Phase ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Well Differentiated

380 Background: Sunitinib was approved by the FDA in 2011 for treatment of progressive, well-differentiated, advanced pancreatic neuroendocrine tumors (pNETs) based on a pivotal phase III study (NCT00428597) that showed a significant increase in progression-free survival (PFS) over placebo following early study termination. Subsequently, the FDA requested a post-approval study to support these findings. Methods: In this open-label, phase IV clinical trial (NCT01525550), patients with progressive, well-differentiated, unresectable advanced/metastatic pNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study. Primary endpoint was investigator-assessed PFS per RECIST 1.0. This study is ongoing. Results: Sixty one treatment-naïve and 45 previously treated patients with progressive pNETs were treated with sunitinib: mean age, 54.6 years; males, 59.4%; white, 63.2%; ECOG PS 0, 65.1% or PS 1, 34.0%; and prior somatostatin analog, 48.1% (treatment-naïve, 39.3%; previously treated, 60.0%). At the data cutoff date, 82 (77%) patients discontinued treatment, mainly due to disease progression (46%). Median duration of treatment was ~11.9 months. Investigator-assessed median PFS (mPFS) was 13.2 months (95% CI, 10.9–16.7) in the overall population, with comparable mPFS in treatment-naïve and previously treated patients (13.2 vs 13.0 months). mPFS per independent radiologic review was 11.1 months (95% CI, 7.4–16.6). Objective response rate (ORR) per RECIST was 24.5%: 21.3% in treatment-naïve and 28.9% in previously treated patients. Median overall survival, although not yet mature, was 37.8 months. Treatment-emergent, all-causality adverse events (AEs) reported by ≥ 20% of all patients included neutropenia, diarrhea, leukopenia, fatigue, hand–foot syndrome, hypertension, abdominal pain, dysgeusia, and nausea. Most common grade 3/4 AEs were neutropenia (22%) and diarrhea (9%). Conclusions: The mPFS of 13.2 months and ORR of 24.5% observed in this study support the outcomes of the pivotal phase III study of sunitinib in pNETs and confirm its activity in this setting. AEs were consistent with known safety profile of sunitinib. Clinical trial information: NCT01525550.

Subgroup analysis by measurable metastatic lesion (ML) number and selected lesion locations (LL) at baseline (BL) in NAPOLI-1: A phase III study of liposomal irinotecan (nal-IRI)±5-fluorouracil/leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 460-460
Author(s):  
Jens T. Siveke ◽  
Richard Hubner ◽  
Teresa Mercade Macarulla ◽  
Andrea Wang-Gillam ◽  
Andrew Peter Dean ◽  
...  
Keyword(s):  
Metastatic Lesion ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Pivotal Phase ◽  
Clear Trend ◽  
Prognostic Effect ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Liposomal Irinotecan ◽  
Post Hoc

460 Background: We report a post hoc, exploratory analysis of pts with BL ML number and LL data who received nal-IRI+5-FU/LV, nal-IRI or 5-FU/LV in NAPOLI-1, a pivotal, phase 3 trial (NCT01494506). nal-IRI+5-FU/LV increased median OS (mOS) vs 5-FU/LV (6.1 vs 4.2 mo [HR=0.67; p=0.012]). Methods: ML (1, 2, 3, >3) and LL were recorded (local investigator) at BL. Pts with >1 LL were counted for each location. Results: 354 of 417 ITT pts had measurable BL ML and 1,080 LL were recorded. There was no clear trend in the percentage of pts with KPS ≥80 in 1- >3 ML (range 87%-95%) or LL (range 89%-94%) subgroups. ML 1 (n=81), 2 (n=65) and 3 (n=24) subgroups were small. nal-IRI+5-FU/LV significantly improved mOS vs. 5-FU/LV in pts with 2/>3 ML (n=184/24); nal-IRI+5-FU/LV had numerically higher mOS vs. 5-FU/LV for all LL (Table). nal-IRI+5-FU/LV had favourable median PFS (mPFS) vs. 5-FU/LV in pts with 1–>3 ML (range 2.0-4.2 vs. 1.4-1.9 mo; HR range 0.35-0.88) and for all LL (range 2.8-4.2 vs. 1.4-2.0 mo; HR range 0.39-0.55). Conclusions: Low pt numbers across groups and repeat counting of pts in LL subgroups preclude firm conclusions on treatment efficacy, pending further analyses. Allowing for these limitations, we detected no clear prognostic effect on outcomes of higher BL ML number or LL in NAPOLI-1 ITT pts. nal-IRI+5-FU/LV improved mOS vs. 5-FU/LV in some ML groups and across LL groups; improvement in mPFS vs. 5-FU/LV in the ITT population was maintained in all subgroups. Clinical trial information: NCT01494506. [Table: see text]

Xyntha®is effective and safe in previously treated patients with severe haemophilia A: Final results of a pivotal phase III study

Haemophilia ◽  
2009 ◽  
Vol 15 (2) ◽  
pp. 635-635
Author(s):  
KATIA EVANS ◽  
ROBERT JANCO ◽  
CHANDRASEKHAR UDATA ◽  
AMANDA O’BRIEN ◽  
BROOKE HAYWARD ◽  
...  
Keyword(s):  
Phase Iii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Pivotal Phase ◽  
Phase Iii Study ◽  
Previously Treated Patients ◽  
Previously Treated

Pemetrexed Therapy for Malignant Pleural Mesothelioma

2005 ◽  
Vol 39 (4) ◽  
pp. 678-683 ◽  
Author(s):  
Katarzyna Puto ◽  
Jody S Garey
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Data Extraction ◽  
Relevant Information ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Pivotal Phase ◽  
Pyrimidine Synthesis ◽  
Study Selection ◽  
Phase Iii Study ◽  
American Society

OBJECTIVE: To review pemetrexed, a novel multi-targeted antifolate agent. DATA SOURCES: A literature search was conducted (1985–September 2004) using MEDLINE and CANCERLIT. Recent abstracts from the American Society of Clinical Oncology were also included, along with the manufacturer's information. Key words were pemetrexed, LY-231514, Alimta, multi-targeted antifolate, malignant pleural mesothelioma. STUDY SELECTION AND DATA EXTRACTION: Relevant information on pharmacology, pharmacokinetics, and safety and efficacy of pemetrexed from clinical trials was selected. DATA SYNTHESIS: Pemetrexed inhibits folate metabolism and purine/pyrimidine synthesis. Based on Phase I and II trials, pemetrexed has antitumor activity in solid tumors such as lung, colorectal, and cervical. A pivotal Phase III study in patients with malignant pleural mesothelioma (MPM) demonstrated survival superiority of pemetrexed—cisplatin regimen versus cisplatin. CONCLUSIONS: Pemetrexed is a promising new drug for the treatment of solid malignancies, most notably MPM.

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