The Remittive Effects of Alefacept

2004 ◽  
Vol 8 (2_suppl) ◽  
pp. 10-13 ◽  
Author(s):  
Gerald G. Krueger
Keyword(s):  
Objective Measure ◽  
Severity Index ◽  
Response To Treatment ◽  
Physician Global Assessment ◽  
Phase 2 ◽  
Trial Duration ◽  
Phase 3 ◽  
Two Phase ◽  
Phase 2 Trial ◽  
Duration Of Response

The duration of response to treatment with alefacept has been assessed in patients with moderate to severe chronic plaque psoriasis who responded to alefacept therapy in phase 2 and phase 3 clinical studies. In a phase 2 trial, duration of response was based on time to retreatment with alefacept. In two phase 3 studies, the more objective measure of maintenance of a ≥50% reduction from baseline Psoriasis Area and Severity Index (PASI 50) was used. Two patient subsets were analyzed: (1) those who achieved a PASI 75 at any time during the trials and (2) those who achieved a Physician Global Assessment of “clear” or “almost clear” at any time during the trials. Regardless of the criterion used or the route of alefacept administration (intravenous or intramuscular), the median duration of response to alefacept therapy ranged from 7 to 10 months across the three studies. Alefacept is a remittive therapy for psoriasis.

Nivolumab plus cabozantinib in patients with non-clear cell renal cell carcinoma: Results of a phase 2 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4509-4509
Author(s):  
Chung-Han Lee ◽  
Martin H Voss ◽  
Maria Isabel Carlo ◽  
Ying-Bei Chen ◽  
Eduard Reznik ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Clear Cell ◽  
Phase 2 ◽  
Phase 3 ◽  
Cell Renal Cell Carcinoma ◽  
Stage Design ◽  
Phase 2 Trial ◽  
Clear Cell Rcc ◽  
Grade 3

4509 Background: Cabozantinib plus nivolumab (CaboNivo) improved objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) over sunitinib in a phase 3 trial for metastatic clear cell renal cell carcinoma (RCC). (Choueiri, abstract 6960, ESMO 2020) We report the results of a phase 2 trial of CaboNivo in patients (pts) with non-clear cell RCC. Methods: Pts had advanced non-clear cell RCC, 0 or 1 prior systemic therapies excluding prior immune checkpoint inhibitors, and measurable disease by RECIST. Cabo 40 mg/day plus Nivo 240 mg every 2 weeks or 480 mg every 4 weeks was given across two cohorts. Cohort 1: papillary, unclassified, or translocation associated RCC; Cohort 2: chromophobe RCC. The primary endpoint was ORR by RECIST; secondary endpoints included PFS, OS, and safety. Cohort 1 was a single stage design that met its primary endpoint and was expanded to produce more precise estimates of ORR. Cohort 2 was a Simon two-stage design that closed early for lack of efficacy. Correlative analyses by next generation sequencing were performed and to be presented. Results: A total of 40 pts were treated in Cohort 1, and 7 pts were treated in Cohort 2 (data cutoff: Jan 20, 2021). Median follow up time was 13.1 months (range 2.2 – 28.6). In Cohort 1, 26 (65%) pts were previously untreated, and 14 (35%) pts had 1 prior line: 10 (25%) received prior VEGF-targeted therapy and 8 (20%) received prior mTOR-targeted therapy. ORR for Cohort 1 was 48% (95% CI 31.5–63.9; Table). Median PFS was 12.5 months (95% CI 6.3–16.4) and median OS was 28 months (95% CI 16.3–NE). No responses were seen among 7 patients in Cohort 2 with chromophobe histology (Table). Grade 3/4 treatment emergent adverse events were consistent with that reported in the phase 3 trial; Grade 3/4 AST and ALT were 9% and 15%, respectively. Cabozantinib and nivolumab were discontinued due to toxicity in 17% and 19% of pts, respectively. Conclusions: CaboNivo had an acceptable safety profile and showed promising efficacy in metastatic non-clear cell RCC pts with papillary, unclassified, or translocation associated histologies whereas activity in patients with chromophobe RCC was limited. Clinical trial information: NCT03635892. [Table: see text]

Effects of Trial Duration on Intrasession Reliability of Single Leg Balance Testing on Stable and Unstable Surfaces

2017 ◽  
Vol 26 (6) ◽  
Author(s):  
Bryan L. Riemann ◽  
Kelsey Piersol ◽  
George J. Davies
Keyword(s):  
Center Of Pressure ◽  
Phase 1 ◽  
Intraclass Correlation ◽  
Correlation Coefficients ◽  
Phase 2 ◽  
Single Trial ◽  
Trial Duration ◽  
Phase 3 ◽  
Intraclass Correlation Coefficients ◽  
Balance Testing

Context: Single leg balance testing is a commonly used tool in sports medicine; however, there has been no consensus on trial duration needed to obtain reliable measures. Objective: This investigation sought to determine the minimum trial duration required to obtain the highest intrasession single and average trial reliability for single leg balance testing on stable and unstable surfaces using dominant and nondominant limbs. Design: Intrasession reliability.Setting:Biomechanics laboratory. Participants: 70 healthy (35 men, 35 women), physically active young adults aged 22.8 ± 2.8 y divided into 3 subgroups (n = 10, 30, 30) across a 3-phase study. Methods:3 phases of single leg balance testing were performed. For phase 1, the duration of time each participant could maintain posture on each limb/surface were computed. Phase 2 considered performance for 6 cumulative time intervals (5s, 10s, 15s, 20s, 25s, 30s). Phase 3 served to solidify results of phase 2 by computing reliability of 15s trials. Main outcome measures: Overall stability index of the center of pressure and platform tilt. Results: Intraclass correlation coefficients for phase 2 ranged from .74 (5s interval for nondominant limb on unstable surface) to .94 (20s interval for nondominant limb on stable surface). Phase 3 intraclass correlation coefficients ranged from .66 to .78 for single trial and .85 to .92 for 3 trial average with coefficients of variation ranging from 23.9% to 40.4% for single trial and 13.8% to 23.0% for 3 trial average. Conclusions:These results ultimately suggest 15s as the optimal trial duration to provide reliable measures while reducing compensatory event occurrence.

Are There Circumstances in Which Phase 2 Study Results Should Be Practice-Changing?

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 489-492 ◽  
Author(s):  
Marcie R. Tomblyn ◽  
J. Douglas Rizzo
Keyword(s):  
Clinical Trials ◽  
Treatment Modalities ◽  
Phase 2 ◽  
Phase 3 ◽  
Randomized Controlled Clinical Trials ◽  
Phase 2 Trial ◽  
Treatment Indications ◽  
Study Results ◽  
Patient Resources ◽  
Large Phase

Abstract New pharmaceuticals, innovative combinations of approved agents, and novel treatment modalities have resulted in a marked increase in the need for clinical trials. Evidence for treatment efficacy is best derived from large phase 3 randomized, controlled clinical trials. However, phase 3 investigations are lengthy and expensive, and consume patient resources. Furthermore, some diseases and treatment indications are rare, and adequate numbers of patients for a definitive phase 3 trial do not exist. Consequently, it is imperative for clinicians to understand phase 2 trial design, since their interpretation is required to apply the findings in clinical practice appropriately. The complexity of phase 2 studies is explored, including unique designs, possible use of randomization, and other key elements necessary for interpretation of phase 2 trials. Specific examples and application of these concepts are discussed in this review.

The Brigham Scalp Nail Inverse Palmoplantar Psoriasis Composite Index (B-SNIPI): A Novel Index to Measure All Non-plaque Psoriasis Subsets

2014 ◽  
Vol 41 (6) ◽  
pp. 1230-1232 ◽  
Author(s):  
Mital Patel ◽  
Stephanie W. Liu ◽  
Abrar Qureshi ◽  
Joseph F. Merola
Keyword(s):  
Plaque Psoriasis ◽  
Composite Index ◽  
Objective Measure ◽  
Severity Index ◽  
Chronic Inflammatory Disease ◽  
Response To Treatment ◽  
Psoriatic Skin ◽  
Patient Reported ◽  
Significant Impairment

Psoriasis is a chronic inflammatory disease that encompasses a large spectrum of clinically distinct subtypes. Although chronic plaque psoriasis is reported as the most common form of psoriatic skin disease, there is growing evidence that other variants including scalp, nail, inverse, and palmoplantar psoriasis are prevalent, undertreated, and associated with significant impairment in quality of life. Currently, the Psoriasis Area and Severity Index (PASI) is the standard to assess psoriasis severity as well as response to treatment; however, the PASI has several limitations. In response to this need and as a complementary objective measure to the PASI, we created the Brigham Scalp Nail Inverse Palmoplantar Psoriasis Composite Index (B-SNIPI), based on patient-surveyed, patient-reported outcomes equally weighted with physician assessment of disease activity. Herein we summarize the B-SNIPI as presented at the 2013 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

scholarly journals Exposure-Response Relationships for Efficacy and Safety of Filgotinib and its metabolite GS-829845 in Subjects with Rheumatoid Arthritis Based on Phase 2 and Phase 3 Studies

2021 ◽  
Author(s):  
Amy Meng ◽  
Kacey Anderson ◽  
Cara Nelson ◽  
Liyun Ni ◽  
Shu-Min Chuang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Therapeutic Effects ◽  
Phase 2 ◽  
Phase 3 ◽  
Two Phase ◽  
Once Daily ◽  
Exposure Response ◽  
Daily Dose

Aims:Filgotinib is a potent, oral, JAK1-preferential inhibitor for the treatment of rheumatoid arthritis (RA). This report describes exposure-response (ER) analyses of filgotinib for dose confirmation based on three Phase 3 and two Phase 2 studies in moderate to severe RA patients. Methods:The PK exposures used in ER analyses were derived from population pharmacokinetic analysis. The relationship between filgotinib exposures and various efficacy endpoints (ACR20/50/70 and DAS28) was assessed over octile groups of exposures by using combined exposures of filgotinib and GS-829845 (major, active metabolite). For the ER analyses of safety, exposures were examined between subjects who experienced and who did not experience the evaluated safety events, which was conducted separately for filgotinib and GS-829845. Results:Exposure efficacy relationships consistently revealed high response rates across the exposure range for filgotinib 200 mg once daily dose. A trend of increasing response with increasing exposure was observed over the exposure range for the primary and multiple secondary efficacy endpoints, with exposures associated with the 200 mg dose primarily residing on the curve plateau. For exposure-safety analyses, filgotinib and GS-829845 exposures were similar irrespective of presence/absence of the evaluated safety endpoints, indicating no exposure-safety relationship for common TEAEs, common laboratory abnormalities, serious TEAEs, or serious infections. Conclusions:ER analyses confirmed that filgotinib produced more robust therapeutic effects across the exposure range observed at 200 mg once daily compared to lower doses. The positive exposure-efficacy relationship and a lack of exposure-safety relationship on the evaluated safety endpoints supported the 200 mg once daily dose for commercialization.

scholarly journals Impact of age on the efficacy and safety of peficitinib (ASP015K) for the treatment of rheumatoid arthritis

2021 ◽  
Author(s):  
Yoshiya Tanaka ◽  
Tsutomu Takeuchi ◽  
Daisuke Kato ◽  
Yuichiro Kaneko ◽  
Musashi Fukuda ◽  
...  
Keyword(s):  
Herpes Zoster ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Incidence Rates ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Two Phase ◽  
Related Disease ◽  
Serious Infections

ABSTRACT Objectives To evaluate peficitinib efficacy and safety in Asian patients with rheumatoid arthritis (RA), stratified by age (≥20–<50, ≥50–<65, and ≥65 years). Methods Efficacy data from two Phase 3 studies were analysed. Safety data from one Phase 2, two Phase 3, and one open-label extension study were pooled. Incidence rates per 100 patient-years of adverse events of special interest were calculated, and Cox proportional hazard analysis was conducted. Results 1052 patients received peficitinib for 2 years (median). Peficitinib demonstrated efficacy improvements versus placebo across all age categories. Incidence rates (95% confidence interval) per 100 patient-years for ≥20–<50, ≥50–<65, and ≥65 years were 0.8 (0.4, 1.9), 2.6 (1.8, 3.7), and 4.7 (3.1, 7.0) for serious infections and 3.7 (2.5, 5.4), 6.4 (5.0, 8.2), and 11.2 (8.5, 14.7) for herpes zoster–related disease, respectively. Twenty patients reported malignancies in pooled Phase 2/3 studies. Incidences of serious infections and herpes zoster–related disease increased significantly with age, but there was no association with baseline estimated glomerular filtration rate. Conclusions Peficitinib was efficacious in adult Asian RA patients of all ages. Age, but not estimated glomerular filtration rate, was associated with serious infections and herpes zoster–related disease, demonstrating the importance of an appropriate RA treatment strategy in older patients.

The transition from phase II to phase III studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6514-6514 ◽  
Author(s):  
I. Tannock ◽  
A. Gulamhusein ◽  
D. R. Berthold
Keyword(s):  
Phase Ii ◽  
Phase Iii ◽  
Phase 2 ◽  
Phase Ii Trials ◽  
Phase 3 ◽  
Phase 2 Trial ◽  
Time Period ◽  
Phase 2 Study ◽  
New Treatment ◽  
Background Phase

6514 Background: Phase II trials are performed to detect potential anti-tumor effects of a new treatment and should be used to decide whether to proceed to a phase 3 trial or not. However, many phase 2 trials never lead to a phase 3 trial despite encouraging results. Here we sought to determine how often (i) positive phase 2 trials have led to phase 3 trials, and (ii) how often phase 2 trials were designed to lead to a phase 3 trial. Methods: We reviewed 200 phase 2 trials, presented at ASCO meetings in 1995–1996, and 2006, selecting randomly 20 abstracts with encouraging results for 5 cancer sites (breast, lung, GI, GU, Gyn) in each time period. For those presented in 1995–1996, we searched systematically for subsequent randomized studies where one treatment arm was similar to that in the phase 2 study. For those presented in 2006, a questionnaire was sent to authors asking whether they recommend evaluating the regimen in a phase 3 trial, whether a phase 3 trial is planned and whether resources (budget, patients, drugs) are available to conduct a phase 3 trial. Results: Ten years after presenting phase 2 trials with positive results, only 13 regimens have been evaluated in a phase 3 trial. Of 100 investigators who presented a phase 2 trial in 2006, 42 returned the questionnaire, 36 confirmed that the results met criteria of efficacy and 25 thought the regimen should be evaluated in a phase 3 trial. Only 10 investigators plan to undertake a phase 3 trial, and 8 stated they had resources to do so. Reasons for not planning a phase 3 study included insufficient efficacy (7), insufficient access to patients (5) or financial support (5), lack of interest from colleagues (6), and lack of support from the company (8). Conclusions: Few (∼13%) phase 2 trials with promising activity are followed by phase 3 trials and this is not increasing with time. Reasons include lack of resources such as money, drugs and patients. Many of these limitations are known when planning the phase 2 study, implying that many phase 2 trials are not planned as precursors of phase 3 trials. Resources spent on such trials would be better applied to practice-changing phase 3 trials. No significant financial relationships to disclose.

A retrospective analysis of data from two trials of sunitinib in patients with advanced renal cell carcinoma (RCC): Pitfalls of efficacy subgroup analyses based on dose-reduction status.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 363-363 ◽  
Author(s):  
Reza Khosravan ◽  
Xin Huang ◽  
Robin Wiltshire ◽  
Mariajose Lechuga ◽  
Robert John Motzer
Keyword(s):  
Dose Reduction ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Cancer Center ◽  
Phase 2 ◽  
Phase 3 ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Trough Concentrations ◽  
Require Dose

363 Background: Patients requiring sunitinib dose reduction who received a novel dose/schedule modification scheme had longer progression-free survival (PFS) than patients who did not require dose reduction and remained on 50 mg Schedule 4/2 (4 weeks on, 2 weeks off) (Bjarnason 2011). Our analysis compared sunitinib efficacy in advanced RCC patients with/without dose reduction using the label-approved, dose-reduction scheme (ie, 50 mg/37.5 mg/25 mg) and schedule (Schedule 4/2) and explored potential causes of any differences. Methods: Data from a Phase 3 and a Phase 2 trial, sunitinib Schedule 4/2 arms only (N=375 and 146, respectively), were retrospectively analyzed, and pharmacokinetics and baseline characteristics of patients with/without dose reduction compared. Results: In the Phase 3 trial, median (95% CI) PFS was 14.0 (13.1–16.2) months (mos) and 8.1 (6.3–10.6) mos with (n=194) and without (n=181) dose reduction, respectively. In the Phase 2 trial, corresponding PFS values were 13.4 (9.8–19.8) mos and 5.8 (3.9–8.5) mos (n=51 and 95, respectively). In the Phase 2 trial, steady-state mean (SD) total drug trough concentrations were 96.0 (42.2) ng/mL and 85.8 (43.4) ng/mL on Day 29 of Cycle 1 in patients with/without dose reduction, respectively. In both studies, the percent of patients with baseline Memorial Sloan-Kettering Cancer Center risk factors of 0 (favorable), 1–2 (intermediate), and 3 (poor) were 37–47%, 53–57% and 0–6% with dose reduction vs. 25–28%, 65–72%, and 0–10% without dose reduction. The mean (range) time to dose reduction was 7.2 (0.03–40.4) mos in the Phase 3 trial and 4.5 (0.4–22.6) mos in the Phase 2 trial. Conclusions: Patients with dose reduction remaining on Schedule 4/2 appeared to have longer PFS than patients with no dose reduction. The differences were not caused by differences in plasma drug exposures; they appeared to be due, at least in part, to 1) differences in patients’ baseline prognostic factors and 2) patients’ PFS or longevity affecting their dose-reduction status. Thus, efficacy subgroup analysis based on patients’ dose-reduction status appears to be confounded, leading to biased results.

Response to treatment with denosumab in patients with giant cell tumor of bone (GCTB): FDG PET results from two phase 2 trials.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 10505-10505 ◽  
Author(s):  
Keith M. Skubitz ◽  
David Morgan Thomas ◽  
Sant P. Chawla ◽  
Arthur P. Staddon ◽  
Jacob Engellau ◽  
...  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Fdg Pet ◽  
Cell Tumor ◽  
Response To Treatment ◽  
Phase 2 ◽  
Two Phase
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