Safety and efficacy study of roxadustat to treat anemia in patients with chronic kidney disease (CKD), not on dialysis.

• Register: EUCTR
• Last refreshed on: 7 January 2019
• Main ID: EUCTR2014-000770-19-HU
• Date of registration: 31/10/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: Safety and efficacy study of roxadustat to treat anemia in patients with chronic kidney disease (CKD), not on dialysis.
• Scientific title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients not on Dialysis
• Date of first enrolment: 06/01/2015
• Target sample size: 2600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000770-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Bulgaria, Canada, Czech Republic, Germany, Hungary, India, Italy, Korea, Republic of, Mexico, Peru, Philippines, Poland, Romania, Russian Federation, Slovakia, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: Information Centre
• Affiliation: AstraZeneca AB

• Name: Information Centre
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
-Age =18 years. - A glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, corresponding to stage 3, 4 or 5 chronic kidney disease (CKD) according to the Kidney Disease Outcomes Quality Initiative, not receiving dialysis. - Mean of 2 most recent central laboratory hemoglobin (Hb) values during the screening period, obtained at least 7 days apart, must be <10.0 g/dL.- Ferritin =50 ng/mL at randomization. - Transferrin saturation =15% at randomization. - Serum folate level = lower limit of normal (LLN) at randomization. - Serum vitamin B12 level =LLN at randomization. - Alanine aminotransferase and aspartate aminotransferase =3 x upper limit of normal (ULN) and total bilirubin =1.5 x ULN at randomization. - Body weight 45 to 160 kg.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1300

Exclusion criteria:
-Any erythropoietin analogue treatment within 6 weeks of randomization.- New York Heart Association Class III or IV congestive heart failure at enrollment- Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.- History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver).- Known hereditary hematologic disease such as thalassemia, sickle cell anemia, a history of pure red cell aplasia or other known causes for anemia other than CKD.- Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis).- Diagnosis or suspicion (e.g. complex kidney cyst of Bosniak Category IIF, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. computerized tomography scan or magnetic resonance imaging conducted at screening or within 12 weeks prior to randomization.- Systolic blood pressure (BP) =160 mmHg or diastolic BP =95 mmHg, within 2 weeks prior to randomization. Patients may be rescreened once BP controlled.- History of prostate cancer, breast cancer or any other malignancy, except the following: cancers determined to be cured or in remission for =5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps.- Positive for any of the following: human immunodeficiency virus, hepatitis B surface antigen or anti-hepatitis C virus antibody.- Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be the principal cause of anemia.- Known hemosiderosis, hemochromatosis or hypercoagulable condition.- Any prior organ transplant or a scheduled organ transplantation date.- Any red blood cell transfusion during the screening period.- Any current condition leading to active significant blood loss.- Any treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor.- Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within at least 1 month of the first administration of investigation product in this study. (Note: patients consented and screened, but not randomized in this study or a previous study are not excluded).- History of alcohol or drug abuse within 2 years prior to randomization. - Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence. - Pregnant or breastfeeding females.- Known allergy to the investigational product or any of its ingredients.- Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound safety or efficacy assessment or may interfere with study participation.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Anemia in chronic kidney disease patients without dialysis.
MedDRA version: 19.0 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Code: AZD9941
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Roxadustat
CAS Number: 808118-40-3
Current Sponsor code: AZD9941
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Code: AZD9941
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Roxadustat
CAS Number: 808118-40-3
Current Sponsor code: AZD9941
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Code: AZD9941
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Roxadustat
CAS Number: 808118-40-3
Current Sponsor code: AZD9941
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. From randomization (week 0) to end of study (event-driven, anticipate 1-2 years).

Secondary Objective: Evaluate the efficacy of roxadustat.

Evaluate the CV safety of roxadustat for the composite endpoint of all cause mortality, non-fatal Myocardial Infarction (MI), non-fatal stroke, heart failure requiring hospitalization and unstable angina leading to hospitalization

Evaluate the CV safety of roxadustat for the composite safety endpoint (CSE) of all cause mortality, non-fatal MI, non-fatal stroke, heart failure requiring hospitalization, unstable angina leading to hospitalization, deep vein thrombosis, pulmonary embolism, vascular access thrombosis or hypertensive emergency

Evaluate the need for rescue therapy

CKD progression

Evaluate the effect of roxadustat on anemia symptoms and health-related quality of life (HRQoL)

Evaluate the effect of roxadustat on self-reported health status.

To evaluate the safety and tolerability of roxadustat

Main Objective: Evaluate the cardiovascular (CV) safety of roxadustat for the treatment of anemia in patients with chronic kidney disease (CKD) not on dialysis therapy.

Primary end point(s): 1. Major adverse cardiovascular (CV) events (MACE): Time to first occurrence of all cause mortality, non-fatal myocardial infarction or non-fatal stroke.

Secondary Outcome(s)

Secondary end point(s): 1. Mean change in hemoglobin (Hb) from baseline to the end of treatment visit (event-driven, anticipate 1-2 years).
2. Proportion of total time of Hb measurements within the interval of 11±1 g/dL from week 28 until end of treatment visit (event-driven, anticipate 1-2 years).
3. MACE+: Time to first occurrence of all cause mortality, non-fatal myocardial infarction (MI) or non-fatal stroke, heart failure requiring hospitalization or unstable angina leading to hospitalization.
4. Time to first occurrence of all cause mortality, non-fatal MI, non-fatal stroke, heart failure requiring hospitalization, unstable angina leading to hospitalization, deep vein thrombosis, pulmonary embolism, vascular access thrombosis or hypertensive emergency.
5. Time-to-first instance of receiving intravenous (IV) iron, red blood cell (RBC) transfusions or erythropoietin analogue as rescue therapy.
6.Change in estimated glomerular filtration rate (eGFR) from baseline to the end of treatment visit(event-driven, anticipate 1-2 years).
7. Changes in anemia symptoms and four disease-specific Health Related Quality of Life (HRQoL) domains as measured by the Funtional Assessment of Cancer Therapy-Anemia (FACT-An). Measured at visit randomization (week 0), week 12, 28 and 52.
8.Changes in generic HRQoL as measured by the Short Form 36 (SF-36) (vers 2, standard). Measured at visit randomization (week 0), week 12, 28 and 52.
9. Changes in self-reported health status as measured by the EuroQol Health Utility Index (EQ-5D-5L) and Patients’ Global Impression of Change (PGIC) measured at baseline, week 12, 28 and 52.
10. Adverse events (AEs), serious adverse events (SAEs) and changes in vital signs, electrocardiogram (ECG) and laboratory values. Measured from the first screening visit to the end of the study (event-driven, anticipated duration 1-2 years).

Timepoint(s) of evaluation of this end point: 1. From baseline to end of study (event-driven, anticipate 1-2 years).
2. From week 28 until end of study (event-driven, anticipate 1-2 years).
3. From randomization (week 0) to end of study (event-driven, anticipate 1-2 years).
4.From randomization (week 0) to end of study (event-driven, anticipate 1-2 years).
5. From randomization (week 0) to end of study (event-driven, anticipate 1-2 years).
6. From baseline to end of study (event-driven, anticipate 1-2 years).
7. Measured at visit randomization (week 0), week 12, 28 and 52.
8. Measured at visit randomization (week 0), week 12, 28 and 52.
9. At baseline, week 12, 28 and week 52
10.From the first screening visit to the end of the study (event-driven, anticipated duration 1-2 years).

Secondary ID(s)

2014-000770-19-CZ

D5740C00001

NCT02174627

Source(s) of Monetary Support

AstraZeneca AB