scholarly journals Correction to: Providing Patients with Critical or Life-Threatening Illnesses Access to Experimental Drug Therapy: A Guide to Clinical Trials and the US FDA Expanded Access Program

2020 ◽  
Vol 34 (4) ◽  
pp. 295-295
Author(s):  
Marjorie A. Speers
Keyword(s):  
Clinical Trials ◽  
Drug Therapy ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Experimental Drug ◽  
The Us ◽  
Life Threatening ◽  
Us Fda ◽  
Access Program

scholarly journals Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients

2020 ◽  
Author(s):  
Michael Joyner ◽  
R. Scott Wright ◽  
DeLisa Fairweather ◽  
Jonathon Senefeld ◽  
Katelyn Bruno ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Large Population ◽  
Serious Adverse Events ◽  
Expanded Access Program ◽  
The Us ◽  
Circulatory Overload ◽  
Life Threatening ◽  
Us Fda ◽  
Safety Metrics ◽  
Access Program

Background: Convalescent plasma is the only antibody based therapy currently available for COVID-19 patients. It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19. Methods: Thus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5,000 hospitalized adults with severe or life threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA Expanded Access Program for COVID-19 convalescent plasma. Results: The incidence of all serious adverse events (SAEs) in the first four hours after transfusion was <1%, including mortality rate (0.3%). Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n=4), transfusion-associated circulatory overload (TACO; n=7), transfusion-related acute lung injury (TRALI; n=11), and severe allergic transfusion reactions (n=3). However, only 2 (of 36) SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The seven-day mortality rate was 14.9%. Conclusion: Given the deadly nature of COVID-19 and the large population of critically-ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.

Expanded Access Program (EAP) for Lenalidomide (Revlimid®) Plus Dexamethasone in over 1400 Subjects with Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3556-3556 ◽  
Author(s):  
Christine Chen ◽  
Donna E. Reece ◽  
David Siegel ◽  
Ruben Niesvizky ◽  
Ralph Vincent Boccia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase Iii ◽  
Advocacy Groups ◽  
Refractory Multiple Myeloma ◽  
Expanded Access ◽  
Prior Therapy ◽  
Expanded Access Program ◽  
The Us ◽  
Grade 3 ◽  
Access Program

Abstract Background: Lenalidomide (Revlimid®) in combination with dexamethasone was approved in the US on June 29, 2006 for the treatment of subjects with multiple myeloma who had received at least one prior therapy. On February 28, 2005 based upon a positive interim analysis of two pivotal placebo-controlled Phase III studies, an independent Data Safety Monitoring Board recommended the studies be unblinded and all subjects in both studies be given access to lenalidomide. In April 2005, the FDA in association with myeloma patient advocacy groups requested Celgene establish an expanded access program to make lenalidomide plus dexamethasone available to subjects with relapsed or refractory multiple myeloma while the treatment was awaiting approval. Aim: To provide lenalidomide to multiple myeloma subjects with a high likelihood of benefit and to obtain additional safety data. Methods: Subjects with relapsed or refractory multiple myeloma that received at least 1 prior therapy were eligible. Subjects received 25 mg lenalidomide plus high-dose dexamethasone in 4-week cycles until disease progression was documented, study drug was discontinued, or lenalidomide became commercially available for this indication. Results: Between September 8, 2005 and July 25, 2006, approximately 1400 subjects in the US and Canada were enrolled into the study. A data snapshot taken March 17, 2006 demonstrated that 746 subjects had been enrolled, median age was 63 years, 60% were male, and 66.5% had Stage III disease. Median time on study was 7.1 weeks (0.1–24.4) and median daily dose was 20.5 mg. At least one Grade 3 or 4 adverse event was reported in 261 (35%) of the 746 subjects. Most commonly reported Grade 3–4 events were neutropenia (7.9% of subjects), thrombocytopenia (6.0%), fatigue (3.6%), anemia (3.5%), pneumonia (3.1%) and hyperglycemia (2.0%). These most commonly reported Grade 3–4 adverse events were the same as those found in the previous pivotal studies, however, their frequencies of occurrence were lower in the current study probably due to ongoing data collection and differences in study maturity. Likewise, the most commonly reported adverse events (all grades) were the same as those reported in the two previous pivotal studies. Conclusion: Preliminary data from this expanded access program in over 1400 subjects with multiple myeloma are consistent with results from two earlier Phase III pivotal studies. The EAP of lenalidomide plus dexamethasone in multiple myeloma represents a model of how government, advocacy groups, healthcare providers and industry can work together to quickly provide treatment to subjects in need while a clearly active treatment regimen is awaiting approval.

Atezolizumab (atezo) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): Safety analysis from an expanded access study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4532-4532
Author(s):  
Joaquim Bellmunt ◽  
Sumanta K. Pal ◽  
Hanzhe Zheng ◽  
Darren Tayama ◽  
Dannis Chang ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Clinical Activity ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Fda Approval ◽  
The Us ◽  
Metastatic Urothelial Carcinoma ◽  
Access Program ◽  
Clinical Trial Information ◽  
Efficacy Population

4532 Background: A majority of mUC pts progress on standard platinum-based chemo regimens. Atezo (anti–PD-L1) was approved in the US for mUC in the post-platinum setting. Here we report the preliminary safety results from an expanded access program conducted to grant access to atezo, prior to commercial availability, to a broader range of mUC pts than are typically eligible for Phase I-III studies. Methods: From Nov 2015-Aug 2016, this study (NCT02589717) enrolled mUC pts who progressed during or following platinum. Atezo was given 1200 mg IV q3w, and pts could be treated post RECIST v1.1 PD until lack of clinical benefit (per investigator). Safety and clinical activity were key endpoints. PD-L1 expression on immune cells (IC) was assessed with the VENTANA SP142 IHC assay on the first 73 pts prior to protocol amendment omitting this requirement. This study was ended early following FDA approval of atezo. Results: 218 pts were enrolled at 36 sites in the US, with 214 treated pts comprising the safety/efficacy population (Table). Median treatment duration was 9 wks (range 3-26), corresponding to a median of 3 doses of atezo (range 1-8). Overall, 89% of pts had an AE. Treatment-related AEs (TRAEs) occurred in 46% (any Gr) and 7% (Gr3-4) of pts; 2 treatment-related Gr 5 AEs were seen (ileus; acute respiratory failure). TRAEs ≥ 5% were fatigue, decreased appetite and anemia. TRAEs leading to dose interruption or discontinuation occurred in 11% and 6% of pts, respectively. Investigator-assessed RECIST v1.1 ORR was 15% (95% CI: 9, 23), and disease control rate (ORR + SD) was 49% (95% CI: 40, 59). Additional clinical data will be reported. Conclusions: In this expanded access study, atezo was administered to > 200 mUC pts. Overall, atezo was safe and tolerable, supporting its use in a wider platinum-based population. Clinical trial information: NCT02589717. [Table: see text]

Ipilimumab (Ipi) expanded access program (EAP) for patients (pts) with stage III/IV melanoma: 10 mg/kg cohort interim results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8508-8508 ◽  
Author(s):  
Omid Hamid ◽  
Wen-Jen Hwu ◽  
Jon M. Richards ◽  
Jeffrey S. Weber ◽  
Jedd D. Wolchok ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Stage Iii ◽  
Controlled Clinical Trials ◽  
Serious Adverse Events ◽  
Safety Database ◽  
Expanded Access Program ◽  
Unresectable Stage ◽  
The Us ◽  
Access Program

8508 Background: The EAP (CA184-045), begun in 8/07, currently provides the largest safety database for Ipi outside of controlled clinical trials (CCTs) and included pts with brain metastases (BM) and primary ocular (OM) and mucosal (MM) melanoma. The EAP was amended in 10/08 to administer a 3 mg/kg dose based on the current label (Hodi et al. NEJM 2010). We now report interim data from pts treated in the US at 10 mg/kg from 8/07-10/08. Methods: Pts with unresectable Stage III or IV melanoma who progressed on at least 1 systemic therapy or had no alternate treatment options were eligible. Pts received 10 mg/kg Ipi i.v. q 3 wks up to 4 doses (induction) followed by 10 mg/kg q 12 wks (maintenance) until no longer clinically benefiting or unacceptable/unmanageable toxicity occurred. All serious adverse events (SAEs) and on-study deaths were collected; overall survival (OS) was assessed retrospectively. Results: Of 906 treated pts, 830 were included in the analysis; 39 from prior Ipi trials + 37 from sites whose IRB did not agree to collect OS were excluded. Pts got a median of 4 doses; 31% got ≥5 doses. ECOG 0/1/2 was 53%/39%/8% (1 pt was ECOG 3); 27% had BM, 5% had OM, and 4% MM. Primary reasons for discontinuation were disease progression (67%) and drug toxicity (11%). Incidence of drug-related SAEs was 27% with diarrhea 10%, colitis 8%, endocrinopathies 4%, and dermatitis 0.8%. 2 pts (0.24%) had on-study hepatitis SAEs, both considered drug-related and resulted in discontinuation. There were 3 (0.36%) drug-related intestinal perforations. 2 deaths (0.24%) were the outcome of drug-related SAEs; 1 multi-organ failure and 1 acute respiratory distress syndrome (both ≤70 days from last induction dose). 72 (9%) pts currently remain on treatment (i.e. >3 years). Available OS data showed that 138 pts (17%) were still at risk after 3 years. For 27% of pts the last known alive date was >30 days before data cutoff (with most >2 yrs). Conclusions: Data from the US EAP must be interpreted with caution compared to CCTs. To date, incidence of SAEs for hepatitis and intestinal perforation, and drug-related death at 10 mg/kg Ipi monotherapy is consistent with that seen in BMS clinical trials. Durable OS (>3 yrs) was observed in at least 17% of pts.

Access to innovation through the French Expanded-Access Program and clinical trials in patients with malignant melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22030-e22030
Author(s):  
Claire Christen ◽  
Laetitia Belgodere ◽  
Bernard Guillot ◽  
Ghania Kerouani-Lafaye ◽  
Liora Brunel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Malignant Melanoma ◽  
Early Stage ◽  
Objective Response ◽  
Time Data ◽  
National Agency ◽  
Innovative Drug ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Access Program

e22030 Access to innovation through the French Expanded-Access Program and clinical trials in patients with malignant melanoma Background: The arrival of immunotherapy (IT) and targeted therapy (TT) has constituted a revolution in the treatment of metastatic melanoma (MM) since the 2010s. The major challenge was to allow these new treatments to make them available as soon as possible. France has effective tools such as clinical trials (CT) and an expanded-access program (EPA) (through temporary use authorizations (ATU) and temporary use recommendations (RTU)) allowing the use of innovative drug without marketing authorization (MA) in case of therapeutic “dead-end”. Methods: Real-time data collection of nominal and cohort ATU, RTU (between 01/09/2009 and 01/09/2019), and CT authorizations (from 01/12/2017 to 01/09/2019) filed and evaluated by the French national agency for medicines and health products safety (ANSM) in the MM from internal databases. Clinical data of the cATU come from the summary reports produced by the laboratory. Results: 45 CT were authorized in MM, including 51% in early phases and 44% in phase II/III, mainly in the metastatic stage (86%) and with an industrial promoter (73%). IT and TT (63% and 24% respectively) are the most used in experimental arms, mostly in combination. Through the EPA, 3 RTUs were authorized in the adjuvant treatment of MM, 14 drugs benefited of a nATU and 5 obtained a cATU. This has treated 6538 patients (28% of nATU and 72% of cATU). The anti-PD1 and combination therapy of BRAF and MEK inhibitors are the most used, mainly in combination. 80% of the indications are from the second line. The duration of availability of the ATU is 9,85 months before obtaining the MA. Efficacy data in patients receiving cATU of vemurafenib and combination of cobimetinib and vemurafenib showed respectively the following objective response rate (ORR): at 8 weeks of treatment, ORR = 57,7% and 54,7%; at 20 weeks, ORR = 36,7% and 54,7% (IR criteria). For pembrolizumab, at 12 weeks, ORR = 29,7% and at 24 weeks, ORR = 40% (irRC criteria). All of these drugs obtained a MA and an inscription on the reimbursement list after the health technology assessment. Conclusions: Thanks to CT and the French EPA, patients were able to benefit from innovative treatments at an early stage of MM.

scholarly journals Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (12) ◽  
pp. e1003872
Author(s):  
Jonathon W. Senefeld ◽  
Patrick W. Johnson ◽  
Katie L. Kunze ◽  
Evan M. Bloch ◽  
Noud van Helmond ◽  
...  
Keyword(s):  
United States ◽  
Clinical Trials ◽  
The United States ◽  
Registry Study ◽  
National Hospital ◽  
Expanded Access Program ◽  
Hospital Referral ◽  
Life Threatening ◽  
Widespread Access ◽  
Access Program

Background The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. Methods and findings Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician–principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had—or were at risk of progression to—severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. Conclusions These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. Trial registration ClinicalTrials.gov NCT#: NCT04338360.

scholarly journals Use, Safety, and Efficacy of Single-Patient Use of the US Food and Drug Administration Expanded Access Program

JAMA Oncology ◽  
2019 ◽  
Vol 5 (4) ◽  
pp. 570 ◽  
Author(s):  
Noah Z. Feit ◽  
Debra A. Goldman ◽  
Evan Smith ◽  
Jenny Deighan ◽  
Alexia Iasonos ◽  
...  
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
Single Patient ◽  
Safety And Efficacy ◽  
Expanded Access ◽  
Expanded Access Program ◽  
The Us ◽  
Patient Use ◽  
Access Program

Ensuring Justice in Access to Investigational Neurological Drugs

2018 ◽  
Vol 38 (05) ◽  
pp. 583-588
Author(s):  
Alison Bateman-House ◽  
Arthur Caplan ◽  
Lisa Kearns
Keyword(s):  
Clinical Trials ◽  
Ethical Issues ◽  
Pilot Project ◽  
Investigational Drug ◽  
Medical Products ◽  
Experimental Drugs ◽  
Expanded Access Program ◽  
Investigational Drugs ◽  
Life Threatening ◽  
Access Program

AbstractPatients who suffer from life-threatening illnesses or are stricken with conditions that could result in serious morbidity who have exhausted all appropriate treatments may choose to try, through the Food and Drug Administration's expanded access program, an investigational drug or device in development. The program has succeeded for decades in allowing patients to access potentially helpful but still experimental agents. Nevertheless, the administration of investigational drugs outside of clinical trials raises several ethical issues. Of particular concern are the validity of informed consent and the absence of a framework to ensure that experimental drugs are allocated justly and transparently. Although there are some safeguards to help protect the soundness of consent, little work to date has been done to guarantee that investigational medical products are allocated justly and transparently. We introduce a novel pilot project that seeks to address this issue.

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