AnemiaPhase 3NCT02174731
Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease, on Dialysis.
A Phase 3 study testing Roxadustat and Epoetin alfa in people with Anemia, run by AstraZeneca at 188 sites in 18 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of roxadustat compared to epoetin alfa for the treatment of anemia in chronic kidney disease patients on dialysis. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Anemia
- What is being tested?
- Roxadustat and Epoetin alfa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,133 participants
- Where
- 188 sitesin 18 countries
- Study dates
- 1 Jul 2014to 26 Sep 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of Informed Consent prior to any study specific procedures
- Age ≥18 years at screening visit 1
- Previous versions of the protocol prior to US amendment ver 6.0 and outside of US amendment ver 7.0:
- Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease (ESRD) at least 30 days prior to visit 1. Patients treated with hemodialysis must have access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter. Patients on peritoneal dialysis must have a functioning peritoneal dialysis catheter in place.
- Starting with US amendment ver. 6.0 and outside of US amendment ver 7.0 (changed to recruit incident dialysis patients only):
- Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease (ESRD) for a minimum of 2 weeks and a maximum of 4 months prior to randomization. Patients treated with hemodialysis must have access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter. Patients on peritoneal dialysis must have a functioning peritoneal dialysis catheter in place.
Show all 13Show fewer
- Two central laboratory Hb values during the screening period, obtained at least 7 days apart, must be <12 g/dL in patients currently treated with an erythropoietin analogue or <10 g/dL in patients not currently treated with an erythropoietin analogue. Patients are considered not currently treated if they have not received either Mircera® for at least 8 weeks or any other erythropoietin analogue for at least 4 weeks prior to visit 1.
- Ferritin ≥100 ng/mL at randomization (obtained from screening visit)
- TSAT ≥20% at randomization (obtained from screening visit)
- Serum folate level ≥ lower limit of normal (LLN) at randomization (obtained from screening visit)
- Serum vitamin B12 level ≥ LLN at randomization (obtained from screening visit)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x upper limit of normal (ULN), and total bilirubin (Tbili) ≤1.5 x ULN at randomization (obtained from screening visit)
- Body weight 45 to 160 kg (prescribed dry weight)
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Previous randomisation in the present study
- New York Heart Association Class III or IV congestive heart failure at enrolment
- 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 auto-immune 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
Show all 23Show fewer
- 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. CT scan or MRI) conducted at screening or within 12 weeks prior to randomization.
- Uncontrolled hypertension at the time of randomization (defined as systolic BP ≥180 mmHg or diastolic BP ≥100 mmHg on repeated measurement post-dialysis in hemodialysis patients or at any time in peritoneal dialysis patients), contraindication to epoetin alfa treatment (e.g., pure red cell aplasia, hypersensitivity or know inability to tolerate epoetin alfa)
- 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 (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody (anti-HCV Ab)
- Chronic inflammatory diseases such as rheumatoid arthritis, SLE, 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 with the exception of an autologous renal transplant or a renal transplant that was subsequently removed ("explanted") or scheduled organ transplantation date
- Any red blood cell (RBC) transfusion during the screening period
- Any current condition leading to active significant blood loss
- Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI)
- 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 the month preceding the first administration of IP 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 (see Section 3.8)
- 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 efficacy or safety assessment, or may interfere with study participation
Trial locations and contacts
188 sites in 18 countries.
188 sites in 18 countries
United States51 sites
Research Site
Asheville, North Carolina, 28805
Research Site
Austin, Texas, 78756
Research Site
Austin, Texas, 78758
Research Site
Baton Rouge, Louisiana, 70808
Research Site
Bethlehem, Pennsylvania, 18017
Research Site
Bluefield, West Virginia, 24701
Research Site
Charlotte, North Carolina, 28207
Research Site
Cincinnati, Ohio, 45206
Research Site
Denver, Colorado, 80230
Research Site
East Providence, Rhode Island, 02914
Research Site
El Centro, California, 92243
Research Site
Fairfield, California, 94534
Research Site
Glendale, California, 91205
Research Site
Great Neck, New York, 11021
Research Site
Gulfport, Mississippi, 39501
Research Site
Houston, Texas, 77004
Research Site
Houston, Texas, 77091
Research Site
Huntsville, Alabama, 35805
Research Site
Kansas City, Missouri, 64111
Research Site
Lanham, Maryland, 20706
Research Site
Long Beach, California, 90802
Research Site
Long Beach, California, 90807
Research Site
Los Angeles, California, 90022
Research Site
Los Angeles, California, 90025
Research Site
Lynwood, California, 90262
Research Site
Miami Gardens, Florida, 33169
Research Site
New Haven, Connecticut, 06510
Research Site
Newport News, Virginia, 23605
Research Site
Northridge, California, 91324
Research Site
Ontario, California, 91762
Research Site
Orange, California, 92868
Research Site
Orchard Park, New York, 14127
Research Site
Paterson, New Jersey, 07504
Research Site
Philadelphia, Pennsylvania, 19106
Research Site
Plymouth, Massachusetts, 02360
Research Site
Reno, Nevada, 89511
Research Site
River Forest, Illinois, 60305
Research Site
Riverside, California, 92503
Research Site
Roseville, Michigan, 48066
Research Site
Sacramento, California, 95825
Research Site
San Antonio, Texas, 78212
Research Site
San Antonio, Texas, 78222
Research Site
San Antonio, Texas, 78229
Research Site
Shawnee, Oklahoma, 74804
Research Site
Sterling, Virginia, 20164
Research Site
Sun Valley, California, 91352
Research Site
The Bronx, New York, 10461
Research Site
Whittier, California, 90602
Research Site
Whittier, California, 90606
Research Site
Wichita, Kansas, 67214
Research Site
Wilmington, North Carolina, 28401
Ukraine17 sites
Research Site
Chernivtsi, 58002
Research Site
Dnipro, 49005
Research Site
Ivano-Frankivsk, 76008
Research Site
Ivano-Frankivsk, 76018
Research Site
Kyiv, 01601
Research Site
Kyiv, 02125
Research Site
Kyiv, 04050
Research Site
Kyiv, 04107
Research Site
Odesa, 65025
Research Site
Odesa, 65074
Research Site
Poltava, 36024
Research Site
Ternopil, 46002
Research Site
Uzhhorod, 88006
Research Site
Vinnytsia, 21018
Research Site
Zaporizhzhya, 69001
Research Site
Zaporizhzhya, 69118
Research Site
Zaporizhzhya, 69600
India14 sites
Research Site
Chennai, 600006
Research Site
Ghaziabad NCR, 201012
Research Site
Hyderabad, 500018
Research Site
Kolkata, 700027
Research Site
Lucknow, 226003
Research Site
Maharashtra, 411013
Research Site
Mumbai, 400008
Research Site
Mysore, 570004
Research Site
Nadiād, 387001
Research Site
New Delhi, 110017
Research Site
New Delhi, 110060
Research Site
Pune, 411001
Research Site
Vellore, 632004
Research Site
Vijayawada, 520 008
Russia14 sites
Research Site
Arkhangelsk, 163001
Research Site
Barnaul, 656024
Research Site
Irkutsk, 664049
Research Site
Izhevsk, 426035
Research Site
Kemerovo, 650066
Research Site
Moscow, 105229
Research Site
Moscow, 123182
Research Site
Nizhny Novgorod, 603126
Research Site
Penza, 440034
Research Site
Perm, 614000
Research Site
Pyatigorsk, 357500
Research Site
Ryazan, 390027
Research Site
Saint Petersburg, 191015
Research Site
Ufa, 450071
Bulgaria12 sites
Research Site
Botevgrad, 2140
Research Site
Dupnitsa, 2600
Research Site
Gotse Delchev, 2900
Research Site
Haskovo, 6300
Research Site
Razlog, 2760
Research Site
Samokov, 2000
Research Site
Sandanski, 2800
Research Site
Shumen, 9700
Research Site
Silistra
Research Site
Sliven, 8800
Research Site
Smolyan, 3700
Research Site
Yambol, 8600
Canada12 sites
Research Site
Brampton, Ontario, L6R 3J7
Research Site
Edmonton, Alberta, T6G 2B7
Research Site
Greenfield Park, Quebec, J4V 2H1
Research Site
Kamloops, British Columbia, V2C 2T1
Research Site
Montreal, Quebec, H2X 3J4
Research Site
Montreal, Quebec, H4J 1C5
Research Site
Oshawa, Ontario, L1G 2B9
Research Site
Québec, Quebec, G1R 2J6
Research Site
Saint John, New Brunswick, E2L 4L2
Research Site
Scarborough Village, Ontario, M1P 2V5
Research Site
Sydney, Nova Scotia, B1P 1P3
Research Site
Toronto, Ontario, M3M 0B2
Hungary9 sites
Research Site
Ajka, 8400
Research Site
Budapest, 1076
Research Site
Budapest, 1077
Research Site
Budapest, 1097
Research Site
Debrecen, 4043
Research Site
Miskolc, 3526
Research Site
Nagykanizsa, 8800
Research Site
Székesfehérvár, 8000
Research Site
Tatabánya, 2800
Poland9 sites
Research Site
Ciechanów, 06-400
Research Site
Gmina Końskie, 26-200
Research Site
Katowice, 40-752
Research Site
Lodz, 90-153
Research Site
Lodz, 92-213
Research Site
Pszczyna, 43-200
Research Site
Suwałki, 16-400
Research Site
Tarnów, 33-100
Research Site
Warsaw, 02-758
Czechia8 sites
Research Site
Brno, 625 00
Research Site
Prague, 140 00
Research Site
Prague, 140 21
Research Site
Prague, 190 61
Research Site
Rychnov nad Kněžnou, 516 01
Research Site
Slaný, 274 01
Research Site
Tábor, 390 03
Research Site
Ústí nad Labem, 401 13
Slovakia8 sites
Research Site
Banská Bystrica, 97517
Research Site
Banská Bystrica
Research Site
Bratislava, 82606
Research Site
Bratislava, 831 03
Research Site
Košice, 04011
Research Site
Kráľovský Chlmec, 077 01
Research Site
Nové Zámky, 940 34
Research Site
Zvolen, 960 01
Spain8 sites
Research Site
Almería, 04009
Research Site
Barcelona, 08029
Research Site
Granollers (Barcelona), 08400
Research Site
Málaga, 29010
Research Site
Seville, 41013
Research Site
Seville, 41071
Research Site
Tarragona, 43007
Research Site
Valencia, 46017
Australia7 sites
Research Site
Camperdown, 2050
Research Site
Clayton, 3168
Research Site
Concord, 2139
Research Site
Launceston, 7250
Research Site
Prahan, 3004
Research Site
St Leonards, 2065
Research Site
Wahroonga, 2076
Mexico4 sites
Research Site
Aguascalientes, 20219
Research Site
Guadalajara, 44670
Research Site
México, 06700
Research Site
Veracruz, 91900
Sweden4 sites
Research Site
Karlstad, 651 85
Research Site
Stockholm, 141 86
Research Site
Uppsala, 751 85
Research Site
Västerås, 721 89
Vietnam4 sites
Research Site
Can Tho, 900000
Research Site
Hanoi, 100000
Research Site
Hochiminh, 700000
Research Site
Huế, 530000
Peru3 sites
Research Site
Lima, 14
Research Site
Lima, L27
Research Site
Lima, LIMA 01
Philippines2 sites
Research Site
Cebu City, 6000
Research Site
Iloilo City, 5000
About this study
Official title: A Phase 3, Multicenter, Randomized, Open-label, Active-Controlled Study of the Safety and Efficacy of Roxadustat in the Treatment of Anemia in Dialysis Patients
The purpose of this study is to evaluate the efficacy and safety of roxadustat compared to epoetin alfa for the treatment of anemia in chronic kidney disease patients on dialysis.
Read the detailed description
This is a Phase 3, multicenter, randomized, open-label, active-controlled study to evaluate the efficacy and safety of roxadustat compared to epoetin alfa for the treatment of anemia in dialysis patients. Patients on hemodialysis (HD) or peritoneal dialysis (PD) who have been treated with an erythropoietin analogue or have an indication for treatment with an erythropoietin analogue will be evaluated for eligibility and randomized at a 1:1 ratio to treatment with roxadustat (with discontinuation of prior erythropoietin analogue therapy) or to an active-control group treated with epoetin alfa
- Conditions
- Anemia
- Being tested
- Roxadustat, Epoetin alfa
- Keywords
- Renal,, CKD,, Epoetin alfa,, Roxadustat,, dialysis,, anemia
- Medical subject headings
- Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RoxadustatDrug
Roxadustat will be administered orally three times a week (TIW) to achieve an Hb level of 11 g/dL and maintain a Hb level of 11±1 g/dL.
Epoetin alfaDrug
Epoetin alfa will be administered TIW consistent with approved prescribing information for epoetin alfa to achieve an Hb level of 11 g/dL and maintain a Hb level of 11±1 g/dL.
| Study group | Role | What they receive |
|---|---|---|
| Roxadustat | Experimental | Not described Receives: Drug: Roxadustat |
| Epoetin alfa | Active comparator | Not described Receives: Drug: Epoetin alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52
Baseline Hb was defined as the mean of the three last central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to the participants mean level from Week 28 to Week 52 was analyzed using a missing at random (MAR) based multiple imputation Analysis of Covariance (ANCOVA). Baseline Hb was used as a covariate and treatment group, cardiovascular (CV) history, geographic region and dialysis duration as fixed effects. The adjusted least squares (LS) mean estimates of change from baseline during Week 28 to Week 52 are presented.
Measured: Baseline (Day 1, Week 0), Week 28 to 52
Secondary outcomes (7)
Change in Hb From Baseline to the Mean Level During the Evaluation Period (Week 28 to Week 36) Without Having Received Rescue Therapy Within 6 Weeks Prior to and During the 8-Week Evaluation Period
Baseline Hb was defined as the mean of the three last central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to the participants mean level from Week 28 to Week 36,without having received rescue therapy within 6 weeks prior to and during this 8 week evaluation period was analysed using Mixed Model of Repeated Measures (MMRM). Baseline Hb was used as a covariate and treatment group, CV history, geographic region and dialysis duration as fixed effects. The adjusted LS mean estimates of change from baseline during Week 28 to Week 36 are presented for participants that did not receive rescue therapy within 6 weeks prior to and during this 8-week evaluation period.
Measured: Baseline (Day 1, Week 0), Week 28 to 36
Proportion of Total Time of Hb Within the Interval of >=10 g/dL From Week 28 to Week 52
The proportion of total time was computed as follows: For each participant, the recorded Hb values were first linearly interpolated between measurements. The time this interpolated curve was >=10 g/dL was computed and subsequently divided by the time between the measurements from Week 28 to Week 52. The difference between roxadustat and epoetin alfa were compared using ANCOVA. Baseline Hb was used as a covariate and the treatment groups, CV history, geographic region and dialysis duration as fixed effects.
Measured: Week 28 to 52
Proportion of Total Time of Hb Within the Interval of 10 to 12 g/dL From Week 28 to Week 52
The proportion of total time was computed as follows: For each participant, the recorded Hb values were first linearly interpolated between measurements. The time this interpolated curve was within 10-12 g/dL was computed and subsequently divided by the time between the measurement from Week 28 to 52. The difference between roxadustat and epoetin alfa were compared using ANCOVA. Baseline Hb was used as a covariate and the treatment groups, CV history, geographic region and dialysis duration as fixed effects.
Measured: Week 28 to 52
Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24
Baseline LDL was defined as the last result obtained prior to randomization. Mean changes in LDL cholesterol from baseline to Week 24 was analysed using ANCOVA. Baseline Hb and baseline LDL were used as covariates and treatment groups, CV history, geographic region and dialysis duration as fixed effects. The adjusted LS mean estimates of change from baseline to Week 24 are presented.
Measured: Baseline (Day 1, Week 0) to Week 24
Mean Change in Hb From Baseline to the Participant's Mean Level Between Week 28 to Week 52 in Participants With Baseline High-Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN)
Baseline hsCRP was quantified from stored biomarker samples obtained at randomization. Baseline Hb is defined as the mean of the three last central laboratory Hb values from the screening and randomization visits. Changes in Hb from baseline to mean value during Weeks 28 to 52 in participants with baseline hsCRP >ULN was analyzed using a MAR based multiple imputation ANCOVA. Baseline Hb was used as a covariate and treatment group, CV history, geographic region and dialysis duration as fixed effects. The adjusted LS mean estimates of change from baseline during Week 28 to Week 52 are presented.
Measured: Baseline (Day 1, Week 0), Week 28 to 52
Mean Monthly IV Iron Use From Week 36 to End of Study (EOS)
Oral iron supplementation was allowed for both treatment groups without restriction. Oral iron was recommended for dietary supplementation to support erythropoiesis and as the first line treatment for prevention and treatment of iron deficiency, unless the participant was intolerant to this route of treatment. In participants receiving roxadustat, the Investigator was allowed to initiate the use of an approved IV iron supplement if a participant's Hb value had not sufficiently responded to 2 or more dose increases of the IP, and ferritin <100 nanogram per milliliter (ng/mL) or transferrin saturation (TSAT) <20%. IP treatment was allowed to continue during IV iron administration. Discontinuation of IV iron supplementation was recommended once the participant was no longer considered to be iron deficient (ferritin >100 ng/mL and TSAT >20%).
Measured: Week 36 to EOS (4 weeks after the treatment period)
Time-To-First Administration of RBC Transfusion as Rescue Therapy
Time-to-first RBC transfusion as rescue therapy was calculated as (date of first occurrence of any RBC transfusion as rescue therapy, or date of censoring if no event had occurred) - (date of first dose of IP) + 1. Event rate was calculated as (number of participants with event) divided by (the total number of days at risk for event across all participants in given group divided by 365.25) multiplied by 100. The event rate is presented for participants with events.
Measured: Baseline (Day 1, Week 0) up to EOS (4 weeks after the treatment period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2014 (estimated)
- Study start1 Jul 2014
- Primary completion26 Sep 2018
- Study completion26 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AnemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,133 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Kyntra Bio
- Responsible party
- Sponsor
- Investigators
- Steven Fishbane, MD, Principal investigator, Chief Division of Kidney Diseases and Hypertension, North Shore University Hospital, Great Neck, NY, USAMark Houser, MD, Study director, AZ R&D, Gaithersburg, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02174731
- Sponsor's protocol ID
- D5740C00002
- Status last verified
- Nov 2019
- First submitted
- 24 Jun 2014
- Last updated
- 16 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hamano T, Yamaguchi Y, Goto K, Martin S, Jiletcovici A, Dellanna F, Akizawa T, Barratt J. Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Four Global Roxadustat Phase 3 Trials. Adv Ther. 2024 Apr;41(4):1553-1575. doi: 10.1007/s12325-023-02728-2. Epub 2024 Feb 16.
PubMed 38363466Barratt J, Dellanna F, Portoles J, Choukroun G, De Nicola L, Young J, Dimkovic N, Reusch M. Safety of Roxadustat Versus Erythropoiesis-Stimulating Agents in Patients with Anemia of Non-dialysis-Dependent or Incident-to-Dialysis Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies. Adv Ther. 2023 Apr;40(4):1546-1559. doi: 10.1007/s12325-023-02433-0. Epub 2023 Feb 7.
PubMed 36749544Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
PubMed 36005278Fishbane S, Pollock CA, El-Shahawy M, Escudero ET, Rastogi A, Van BP, Frison L, Houser M, Pola M, Little DJ, Guzman N, Pergola PE. Roxadustat Versus Epoetin Alfa for Treating Anemia in Patients with Chronic Kidney Disease on Dialysis: Results from the Randomized Phase 3 ROCKIES Study. J Am Soc Nephrol. 2022 Apr;33(4):850-866. doi: 10.1681/ASN.2020111638.
PubMed 35361724
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Randomized, Open-label, Active-Controlled Study of the Safety and Efficacy of Roxadustat in the Treatment of Anemia in Dialysis Patients
- ClinicalTrials.gov ID
- NCT02174731
- Acronym / sponsor ID
- D5740C00002
- Conditions
- Anemia
- Keywords
- Renal,, CKD,, Epoetin alfa,, Roxadustat,, dialysis,, anemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,133 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Kyntra Bio
- Study start
- 1 Jul 2014 (actual)
- Primary completion
- 26 Sep 2018 (actual)
- Study completion
- 26 Sep 2018 (actual)
- First posted
- 25 Jun 2014 (estimated)
- Results
- Posted 16 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of roxadustat compared to epoetin alfa for the treatment of anemia in chronic kidney disease patients on dialysis.
Detailed description
This is a Phase 3, multicenter, randomized, open-label, active-controlled study to evaluate the efficacy and safety of roxadustat compared to epoetin alfa for the treatment of anemia in dialysis patients. Patients on hemodialysis (HD) or peritoneal dialysis (PD) who have been treated with an erythropoietin analogue or have an indication for treatment with an erythropoietin analogue will be evaluated for eligibility and randomized at a 1:1 ratio to treatment with roxadustat (with discontinuation of prior erythropoietin analogue therapy) or to an active-control group treated with epoetin alfa
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Roxadustat | Experimental | Drug: Roxadustat |
| Epoetin alfa | Active comparator | Drug: Epoetin alfa |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Provision of Informed Consent prior to any study specific procedures
- Age ≥18 years at screening visit 1
- Previous versions of the protocol prior to US amendment ver 6.0 and outside of US amendment ver 7.0:
- Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease (ESRD) at least 30 days prior to visit 1. Patients treated with hemodialysis must have access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter. Patients on peritoneal dialysis must have a functioning peritoneal dialysis catheter in place.
- Starting with US amendment ver. 6.0 and outside of US amendment ver 7.0 (changed to recruit incident dialysis patients only):
Key exclusion criteria (23 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Previous randomisation in the present study
- New York Heart Association Class III or IV congestive heart failure at enrolment
- 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 auto-immune liver disease, cirrhosis or fibrosis of the liver)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RoxadustatRoxadustat will be administered orally three times a week (TIW) to achieve an Hb level of 11 g/dL and maintain a Hb level of 11±1 g/dL. | Drug | Roxadustat |
| Epoetin alfaEpoetin alfa will be administered TIW consistent with approved prescribing information for epoetin alfa to achieve an Hb level of 11 g/dL and maintain a Hb level of 11±1 g/dL. | Drug | Epoetin alfa |
Primary outcome
Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52
Time frame: Baseline (Day 1, Week 0), Week 28 to 52
Baseline Hb was defined as the mean of the three last central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to the participants mean level from Week 28 to Week 52 was analyzed using a missing at random (MAR) based multiple imputation Analysis of Covariance (ANCOVA). Baseline Hb was used as a covariate and treatment group, cardiovascular (CV) history, geographic region and dialysis duration as fixed effects. The adjusted least squares (LS) mean estimates of change from baseline during Week 28 to Week 52 are presented.
7 secondary outcomes
Change in Hb From Baseline to the Mean Level During the Evaluation Period (Week 28 to Week 36) Without Having Received Rescue Therapy Within 6 Weeks Prior to and During the 8-Week Evaluation Period
Time frame: Baseline (Day 1, Week 0), Week 28 to 36
Proportion of Total Time of Hb Within the Interval of >=10 g/dL From Week 28 to Week 52
Time frame: Week 28 to 52
Proportion of Total Time of Hb Within the Interval of 10 to 12 g/dL From Week 28 to Week 52
Time frame: Week 28 to 52
Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24
Time frame: Baseline (Day 1, Week 0) to Week 24
Mean Change in Hb From Baseline to the Participant's Mean Level Between Week 28 to Week 52 in Participants With Baseline High-Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN)
Time frame: Baseline (Day 1, Week 0), Week 28 to 52
Mean Monthly IV Iron Use From Week 36 to End of Study (EOS)
Time frame: Week 36 to EOS (4 weeks after the treatment period)
Time-To-First Administration of RBC Transfusion as Rescue Therapy
Time frame: Baseline (Day 1, Week 0) up to EOS (4 weeks after the treatment period)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38363466Hamano T, Yamaguchi Y, Goto K, Martin S, Jiletcovici A, Dellanna F, Akizawa T, Barratt J. Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Four Global Roxadustat Phase 3 Trials. Adv Ther. 2024 Apr;41(4):1553-1575. doi: 10.1007/s12325-023-02728-2. Epub 2024 Feb 16.
- Derived from this study: PubMed 36749544Barratt J, Dellanna F, Portoles J, Choukroun G, De Nicola L, Young J, Dimkovic N, Reusch M. Safety of Roxadustat Versus Erythropoiesis-Stimulating Agents in Patients with Anemia of Non-dialysis-Dependent or Incident-to-Dialysis Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies. Adv Ther. 2023 Apr;40(4):1546-1559. doi: 10.1007/s12325-023-02433-0. Epub 2023 Feb 7.
- Derived from this study: PubMed 36005278Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
- Derived from this study: PubMed 35361724Fishbane S, Pollock CA, El-Shahawy M, Escudero ET, Rastogi A, Van BP, Frison L, Houser M, Pola M, Little DJ, Guzman N, Pergola PE. Roxadustat Versus Epoetin Alfa for Treating Anemia in Patients with Chronic Kidney Disease on Dialysis: Results from the Randomized Phase 3 ROCKIES Study. J Am Soc Nephrol. 2022 Apr;33(4):850-866. doi: 10.1681/ASN.2020111638.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
Related trials for Anemia
RecruitingPhase 1/2
The Safety and Efficacy of Daratumumab in Patients With Refractory Aplastic Anemia
Aplastic Anemia, Refractory
Active, not recruitingPhase 1
A Study of YTS109 Cell Injection in Subjects With Relapsed/Refractory Autoimmune Hemolytic Anemia
Autoimmune Hemolytic Anemia, Anti-CD19 STAR T-cell Therapy
Not yet recruitingObservational study
Systematic Intraoperative Cell Salvage in On-Pump Cardiac Surgery Within a Mature Patient Blood Management Programme
Cardiac Surgical Procedures, Blood Transfusion
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
RecruitingObservational study
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
Fanconi Anemia, Inherited Bone Marrow Failure Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Fishbane, MD principal investigator
Chief Division of Kidney Diseases and Hypertension, North Shore University Hospital, Great Neck, NY, USA
Mark Houser, MD study director
AZ R&D, Gaithersburg, USA
188 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Roxadustat and Epoetin alfa in people with Anemia, run by AstraZeneca at 188 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 188 sites in United States, Ukraine, India, Russia, Bulgaria and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 (time frame: Baseline (Day 1, Week 0), Week 28 to 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02174731, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2019.