The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occured first. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. The OLYMPUS, ALPS and ANDES trials evaluated roxadustat vs. placebo in NDD patients. Baseline assessment was the assessment on day 1 (average of the three readings). The OLYMPUS, ALPS and ANDES trials evaluated roxadustat compared to placebo in NDD patients. Participant has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives or limit set by national law, whichever is longer, prior to the initiation of Screening. This was the primary efficacy endpoint for EU (EMA). For each scale scores range from 0-100. Together with the Functional Assessment of Cancer Therapy - General (FACT-G), the Anemia Subscale (AnS) is referred to as the FACT-An Total. No estimation if values were missing. Analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1 visit. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. Today's win in the European Alps trial will help its cause – but a safety analysis of the global pivotal programme, due in early 2019, is what investors are really waiting for. If this value was missing, the latest value prior to first study drug administration was used. Astellas, which has partnered the project in Europe and Japan, did not give many details about the Alps study, except to say it had met its primary endpoints, haemoglobin response rate in the first 24 weeks and haemoglobin change from baseline at weeks 28 to 52. Work productivity and activity impairment: anemic symptoms (WPAI:ANS) questionnaire version 2 was used to measure work and activity impairment during the last seven days due to anemia. All eGFR values collected during the safety emergent period are considered, excluding those collected on or after initiation of dialysis (acute or chronic). Time to First Use of ESA Rescue Therapy during efficacy emergent period. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. The research proposal is reviewed by an Independent Research Panel. Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis (ALPS) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. The mean of the Participant's three most recent Hb values during the Screening period, obtained at least 4 days apart, must be less than or equal to 10.0 g/dL, with a difference of less than or equal to 1.0 g/dL between the highest and the lowest values. If this value was missing, the latest value prior to first study drug administration was used. If baseline value was missing, the value from screening visit was used. The Patients' Global Impression of Change (PGIC) is a participant-rated instrument that measures change in participants overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). The nondialysis CKD trials – OLYMPUS, ANDES, and ALPS – involved 2368 roxadustat and 1865 placebo recipients, both with mean baseline hemoglobin (Hb) values of 9.10 g/dL. The SF-36 scores ranged from 0-100 with higher scores indicating better health status. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. Mean LDL cholesterol <100 mg/dL over weeks 12 to 28 was defined as a binary variable (Yes/No), where Yes was defined as mean LDL cholesterol <100 mg/dL over weeks 12 to 28. First event date was defined as first occurrence of serum creatinine being doubled compared with baseline, first occurrence of chronic dialysis or renal transplant, occurrence of participants who died (whichever occurred first). Time to event was defined as (First event date - Analysis date of first dose intake + 1) / 365.25. The study forms part of a wider large-scale global Phase 3 development program for roxadustat conducted in collaboration with its partner FibroGen, Inc. (NASDAQ: FGEN), and will ultimately support filing and reimbursement in Europe. The Hb values from visit windows from weeks 28 to 36 were used for the calculation of the average regardless of rescue therapy. Questions include asking if participant is working, how many hours the person missed work due to anemic symptoms, how many hours the person missed work due to other reasons, how many hours participant actually worked and how the anemic symptoms impacted their productivity and ability to do daily activities. Participant has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than CKD. Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dosing). Akebia’s vadadustat and Glaxosmithkline’s daprodustat are also in phase III trials, but data are not due until the end of next year at the earliest. Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dosing). HIMALAYAS evaluated roxadustat compared to epoetin alfa in incident dialysis (ID) patients; there were ID patients in ROCKIES and SIERRAS. Baseline assessment was assessment from Day 1 visit. In case of missing data, no imputation rules were applied. They put peak roxadustat revenues at $5.8-8.1bn, depending on the drug’s performance on MACE.  (Clinical Trial), Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor), A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis, 18 Years and older   (Adult, Older Adult), La Fe Santo Domingo, Dominican Republic, 5072, Santiago de los Caballeros, Dominican Republic, 51000, Santo Domingo, Dominican Republic, 103201, Nizhny Novgorod, Russian Federation, 603032, Rostov-on-don, Russian Federation, 344029, Saint Petersburg, Russian Federation, 192242, Saint Petersburg, Russian Federation, 196247, Saint Petersburg, Russian Federation, 197089, Saint-Petersburg, Russian Federation, 194354, Observatory, Cape Town, South Africa, 7925, Bloemfontein, Free State, South Africa, 9324, Durban, Kwa Zulu Natal, South Africa, 4001, Welwyn Garden City, United Kingdom, AL7 4HQ, Westcliff-on-Sea, United Kingdom, SS0 0RY. Patients were given roxadustat twice weekly or TIW in doses ranging from 0.7 and 2.0 mg/kg. The last Hb value must be within 10 days prior to randomization. All scheduled and unscheduled hemoglobin values that belong to each visit window were taken into account using one value per analysis window. Change from baseline in SF-36 PF normalized sub-score compared to the average PF sub-score of weeks 12 to 28. Crucially, there did not appear to be any safety signals. Fibrogen’s roxadustat has its first European win from the Alps trial, but the most important event is still to come. Still, the emergence of biosimilar ESAs would make this tough. This theory will be put to the test when the full phase III programme for roxadustat reads out. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. Clinical Trial Results: A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients not on Dialysis Summary. For participants with use of ESA, the time to first use of ESA was calculated as (First event date - Analysis date of first dose intake + 1) / 365.25. AstraZeneca in CVRM HIMALAYAS evaluated roxadustat compared to epoetin alfa in incident dialysis (ID) patients; there were ID patients in ROCKIES and SIERRAS.” For participants with use of IV iron, the time to first use of IV iron was calculated as (First event date - Analysis date of first dose intake + 1) / 365.25. This suggests that roxadustat provides adistinct pharmacological and clinical profile that may provide a saferand more convenient treatment of CKD anemia. The Hb values from visit windows at weeks 28, 32 and 36 were used for the calculation of the average of weeks 28 to 36. The sum of the durations of all hospitalizations in days was adjusted for the duration of exposure. Higher scores indicate better health status. The safety emergent period was defined as the evaluation period from the analysis date of first drug intake up to 28 days after the analysis date of last dose or end of study (EOS), whichever occurred first. Please remove one or more studies before adding more. Trials in China and Japan have already read out positively, and an approval decision in China is expected by the end of the year. All assessments collected after initiation of chronic dialysis (acute or chronic) are excluded from the analysis. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occurred first. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Baseline was defined as the value on day 1. Readout was delayed earlier this year (More patience needed for novel anaemia class’s biggest test, February 28, 2018). All assessments collected after initiation of dialysis (acute or chronic) were excluded from the analysis. • Strong Fourth Quarter China Roxadustat Net Sales of $29.2 Million and 2020 full-year Net Sales of $72.5 Million • FDA to hold Advisory Committee Meeting on Roxadustat New Drug Application SAN FRANCISCO, March 01, 2021 (GLOBE NEWSWIRE) -- … AstraZeneca in CVRM The First event date was defined as Date of first dose of rescue medication during the efficacy emergent period and Analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1. Participant has a history of alcohol or drug abuse within 2 years prior to randomization. Roxadustat inhibits hypoxia inducible factor (HIF) prolyl hydroxylase activity. Change from BL in SF-36 VT sub-score to the average value in weeks 12-28 was calculated using the physical component scores (PCS) of SF-36. Participants can have more than one hospitalization. Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Europe B.V. ). The FACT-An Total Score scale range is 0-188. Why Should I Register and Submit Results? The OLYMPUS, ALPS and ANDES trials evaluated roxadustat compared to placebo in NDD patients. Participants received roxadustat according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg and 100 mg given TIW to participants weighing more than 70 kg. Participant has a known New York Heart Association Class III or Intravenous (IV) congestive heart failure. By Mark Terry . 1 March 2021 — AstraZeneca and FibroGen, Inc. (FibroGen) today announced that the US Food and Drug Administration (FDA) informed FibroGen that it will convene a meeting of the Cardiovascular and Renal Drugs Advisory Committee to review the new drug application for roxadustat. Leerink analysts noted that roxadustat’s efficacy now looked “more or less certain”. This was the primary efficacy endpoint for US (FDA). Participant's alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels are less than or equal to 3 x upper limit of normal (ULN), and total bilirubin (TBL) is less than or equal to 1.5 x ULN. Clinical trials look at new ways to prevent, detect, or treat disease. Time to first occurrence of hypertension was defined as first date where SBP criterion or DBP criterion is met, whichever occurred first. If baseline value was missing, the value from screening visit was used. FACT-G contains 27 items that cover four dimensions of well-being: physical (PWB) - 7 items, functional (FWB) - 7 items, social/family (SWB) - 7 items, and emotional (EWB) - 6 items. During efficacy emergent period, the mean monthly volume of blood transfused was calculated as the sum of blood volume transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. If this value was missing, the latest value prior to first study drug administration was used. Positive top-line data from the ALPS study confirms the efficacy and safety of roxadustat, a Phase III-stage product which could be the first a new class of orally active agents with potential in the treatment of anemia associated with chronic kidney disease. The Hb values from visit windows at weeks 28, 32, 36, 40, 44, 48 and 52 were used for the calculation of the average of weeks 28 to 52. All scheduled and unscheduled hemoglobin values from weeks 44 to 52 were taken into account for calculating the average values. Participant has a known history of myelodysplastic syndrome or multiple myeloma. Getting a clean safety label will be particularly important if roxadustat is to be used in the less sick non-dialysis-dependent kidney disease population, which the Leerink analysts forecast will account for 45% of the drug’s sales. AstraZeneca in CVRM For participants who experienced more than one hospitalization, only their first event following study treatment was used. The survey measures eight dimensions or scales: (1) physical functioning (PF) (10 items); (2) role limitations due to physical health problems (RP) (3 items); (3) bodily pain (BP) (2 items); (4) social functioning (SF) (2 items); (5) general health perceptions (GH) (5 items); (6) role limitations due to emotional problems (RE) (3 items); (7) vitality, energy or fatigue (VT) (4 items); and (8) mental health (MH) (5 items). Change from baseline to each planned assessment for total cholesterol is reported. Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., pulmonary embolism) within 12 weeks prior to randomization. [18,19] Fibrogen has a lot riding on pivotal data for roxadustat, its project for anaemia in chronic kidney disease. However, these drugs are linked with thromboses and cardiovascular events. Baseline was defined as the value on day 1. Baseline was assessed on Day 1 visit. Roxadustat is an oral HIF-PHI in late-stage development for treatment of CKD anemia. Participant has a diagnosis or suspicion (e.g., complex kidney cyst of Bosniak Category 2F or higher) of renal cell carcinoma on renal ultrasound within 12 weeks prior to randomization. 64 In an open-label phase 2b trial of roxadustat, the most frequent AE (10%) was hypertension requiring a modification to antihypertensive medication. Topline results were announced demonstrating superiority in efficacy vs. placebo in both Hb response rate in the 1st 24 weeks and Hb change from baseline at Weeks 28 to 52. If baseline value was missing, the value from screening visit was used. The First event date was defined as First occurrence of 40% decrease in eGFR from baseline, first occurrence of chronic dialysis or renal transplant (whichever occurred first and Analysis date of first dose intake was defined as date of first study drug dose intake collected on day 1 visit. Data analysis was completed using Kaplan-Meier estimate for cumulative proportion. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. The first event date was defined as the Date of first admission. The change from baseline to the average Hb values across weeks 28 to 52 without having received rescue therapy. But the main questions over the asset now involve its side-effect profile. Talk with your doctor and family members or friends about deciding to join a study. The EQ-5D 5L descriptive system comprises of 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Today's win in the European Alps trial will help its cause – but a safety analysis of the global pivotal programme, due in early 2019, is what investors are really waiting for. The overall safety profile was consistent with results seen in previous roxadustat trials; pooled safety findings were reported in a late breaker abstract at the meeting. Participants without any LDL value within this duration were excluded. A mean blood pressure reduction of 2.6 ± 9.6 mm Hg from baseline was observed in the phase 2b trial of 16 and 24 weeks of treatment with roxadustat. Participant is anticipated to have elective surgery that is expected to lead to significant blood loss or anticipated elective coronary revascularization. Participants received initial dose of roxadustat orally as a tablet in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor that increases endogenous erythropoietin and enhances iron utilization. ROCKIES, SIERRAS and HIMALAYAS, evaluated roxadustat compared to epoetin alfa in DD patients. By using this site, you agree that we may store and access cookies on your device. Late-breaking abstracts explore cardiovascular outcomes of patients with anemia in chronic kidney disease (CKD) treated with roxadustat, including associations with achieved hemoglobin levels and risk of Major Adverse Cardiovascular Events (MACE) and MACE+. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com. Baseline assessment was the assessment from day 1 visit. (NCT02021318) study is a phase III clinical trial which is currently active with an estimated enrollment of approximately 600 participants (Table 2). FibroGen and Astellas anticipate reporting high-level results from their remaining trials in due course. AstraZeneca in CVRM The Hb values from visit windows from weeks 96 to 104 were used for the calculation of the average regardless of rescue therapy. Participant has chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission. Response Yes (responders) was defined as: Hb ≥11.0 g/dL and Hb increase from baseline by ≥ 1.0 g/dL, for participants with baseline Hb > 8.0 g/dL; or Hb increase from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL at two consecutive visits with available data separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (red blood cell (RBC) transfusion, erythropoiesis-stimulating agent (ESA), or intravenous (IV) iron prior to Hb response. Time to first hospitalization was defined in years as the First event date during the Efficacy Emergent Period - (Analysis date of first dose intake +1)/365.25. Roxadustat was dosed TIW throughout the Treatment Period, except if a subject required <20 mg TIW (i.e., <60 mg per week) to maintain Hb levels in the Maintenance Phase, then the dosing frequency could have been reduced in a step-wise fashion (e.g., TIW to BIW, BIW to QW, QW to Q-2 Week [every 2 weeks]). For participants who have experienced more than one RBC transfusion, only their first event following study treatment was used. Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The multi-purpose, short-form health survey has 36 questions with an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. The OLYMPUS, ALPS and ANDES trials evaluated roxadustat compared to placebo in NDD patients. Participant is positive for any of the following: Human Immunodeficiency Virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab). FG-4592 is a new-generation hypoxia-inducible factor prolyl hydroxylase inhibitor in early clinical trials at FibroGen for the oral treatment of iron deficiency anemia and renal failure anemia. Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). Overall work impairment due to ANS was calculated as 100 x Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)]. Data was analysed using Kaplan-Meier estimate for cumulative proportion. Participant has a serum folate level greater than or equal to lower limit of normal at screening. To compute the geometric mean of albumin/creatinine ratio in urine and associated 95% CI, the mean of log-transformed albumin/creatinine ratio in urine values (ratio) and associated 95% CI are back-transformed to the raw scale. This should give Fibrogen and its partners a chance to make the most of their first-mover advantage – if they can get a good safety result. Individual Participant Data (IPD) Sharing Statement: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. HIF causes the physiological response to low oxygen conditions. If roxadustat ends up with a similar label to the ESAs, the former's greater convenience as an oral drug could help it gain market share in the non-dialysis population, Bernstein analysts believe. This study was conducted to treat anemia in patients with chronic kidney disease. The efficacy emergent period was defined as the evaluation period from the analysis date of first dose intake up to 7 days after the analysis date of last dose or EOT visit, whichever occured first. In case of missing data, no imputation rules were applied. HIF-PH inhibitors like roxadustat are designed to stabilise the HIF complex and stimulate endogenous erythropoietin production, effectively mimicking the body’s reaction to high altitude. Participant has been treated with iron-chelating agents within 4 weeks prior to randomization. For the above score, a higher score indicates better QoL. Participant has a history of malignancy, except the following: cancers determined to be cured or in remission for greater than or equal to 5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. The MAP was derived for each visit from the average systolic (SBP) and diastolic blood pressure (DBP) calculated for each visit using the three readings and the following equation: MAP = (2/3) * DBP + (1/3) * SBP. The study consisted of three study periods as follows: Choosing to participate in a study is an important personal decision. Anemia is a reduced number of red blood cells or hemoglobin. In case of missing data, no imputation rules were applied. The OLYMPUS, ALPS and ANDES trials evaluated roxadustat compared to placebo in NDD patients. The physical component score was calculated based on the results of the SF-36 scores. ROCKIES, SIERRAS and HIMALAYAS, evaluated roxadustat compared to epoetin alfa in DD patients. The data evaluated until the safety emergent period, which was defined as the evaluation period from analysis date of first drug intake up to 28 days after the analysis last dose, and results were presented for every 6 months up to 2 years.
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