Anemia in Incident Dialysis PatientsPhase 3HimalayasNCT02052310
Safety and Efficacy Study of Roxadustat (FG-4592) for the Treatment of Anemia in End-Stage Renal Disease (ESRD) Newly Initiated Dialysis Participants
A Phase 3 study testing Roxadustat and Epoetin Alfa in people with Anemia in Incident Dialysis Patients, run by Kyntra Bio at 113 sites in 15 countries.
Trial summary
The purpose of this study is to determine whether roxadustat is safe and effective in the treatment of anemia in participants who have just begun dialysis treatment for ESRD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anemia in Incident Dialysis Patients
- What is being tested?
- Roxadustat and Epoetin Alfa
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,043 participants
- Where
- 113 sitesin 15 countries
- Study dates
- 11 Feb 2014to 21 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines.
- Receiving HD or PD for ESRD for a minimum of 2 weeks and a maximum of 4 months, prior to randomization.
- Hemodialysis access consisting of an arteriovenous (AV) fistula, AV graft, or tunnelled (permanent) catheter; or PD catheter in use.
- Mean of the two most recent predialysis Hb values during the Screening Period, obtained at least 2 days apart, must be ≤ 10.0 g/dL, with a difference of ≤ 1.3 g/dL between the highest and the lowest values. The last Hb value must be drawn within 10 days prior to randomization.
- Ferritin ≥ 100 nanograms (ng)/milliliter (mL) (≥ 220 picomoles (pmol)/L); participants with ferritin level < 100 ng/mL(<220 pmol/L) during screening, qualify after receiving iron supplement (per local standard of care), without the need to retest ferritin prior to randomization.
- Transferrin saturation ≥ 20%; participants with TSAT level < 20% during screening, qualify after receiving iron supplement (per local standard of care), without the need to retest TSAT prior to randomization.
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- Serum folate level, performed within 8 weeks prior to randomization ≥ lower limit of normal (LLN); participants with serum folate level < LLN during screening, qualify after receiving folate supplement (per local standard of care), without the need to retest folate prior to randomization.
- Serum vitamin B12 level, performed within 8 weeks prior to randomization ≥ LLN; participants with vitamin B12 level < LLN during screening, qualify after receiving B12 supplement (per local standard of care), without the need to retest B12 prior to randomization.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3 * upper limit of normal (ULN), and total bilirubin ≤ 1.5 * ULN.
- Body weight up to 160 kg (HD participants: dry weight).
Who cannot join
- Total duration of prior effective ESA use must be ≤3 weeks within the preceding 12 weeks at the time informed consent is obtained.
- Specific dosing guidance, depending on the type of ESAs, injected IV or SC within 12 weeks prior to start of screening are as follows:
- Short-acting ESAs (EPO-alfa or equivalents) - IV: Up to 9 doses, last EPO dose must be ≥2 days prior to start of screening; SC: Up to 3 doses, last EPO dose must be ≥1 week (7 days) prior to start of screening ii) Darbepoetin - IV: Up to 3 doses, last darbepoetin dose must be ≥1 week (7 days) prior to start of screening; SC: Up to 2 doses, last darbepoetin dose must be ≥2 weeks (14 days) prior to start of screening iii) Continuous erythropoietin receptor activator (CERA) IV and SC: Up to 2 doses; last CERA dose must be ≥2 weeks (14 days) prior to start of screening
- Intravenous iron: there is no restriction regarding IV iron use during screening, provided it is administered in accordance with local SOC.
- Red blood cell transfusion within 4 weeks prior to randomization.
- Active, clinically significant infection that could be manifested by white blood cell (WBC) count > ULN, and/or fever, in conjunction with clinical signs or symptoms of infection at the time of randomization.
Show all 33Show fewer
- History of chronic liver disease (for example, chronic infectious hepatitis, chronic auto-immune liver disease, cirrhosis, or fibrosis of the liver).
- New York Heart Association Class III or IV congestive heart failure at screening.
- Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thromboembolic event within a major vessel (excluding vascular dialysis access) (for example, deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
- Uncontrolled hypertension, in the opinion of the Investigator, (for example, that requires a change in anti-hypertensive medication) within 2 weeks prior to randomization.
- Renal imaging performed within 12 weeks prior to randomization indicative of a diagnosis or suspicion (for example, complex kidney cyst of Bosniak Category 2 or higher) of renal cell carcinoma.
- History of malignancy, except for 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 disease that could impact erythropoiesis (for example, systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
- Known, untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration, or retinal vein occlusion (participants who are already blind for the above reasons qualify to participate).
- Known history of myelodysplastic syndrome or multiple myeloma.
- Known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than chronic kidney disease (CKD).
- Known hemosiderosis, hemochromatosis, coagulation disorder, or a hypercoagulable condition.
- Organ transplant: participants with any of the following:
- Experienced rejection of a transplanted organ within 6 months of transplantation
- Currently on high doses of immunosuppressive therapy (per discretion of the Investigator)
- Scheduled for organ transplantation. Note: being on a waiting list for kidney transplant is not exclusionary
- Anticipated elective surgery, except for vascular access surgery or dialysis catheter placement, that is expected to lead to significant blood loss, or anticipated elective coronary revascularization.
- Active or chronic gastrointestinal bleeding.
- Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).
- Use of iron-chelating agents within 4 weeks prior to randomization.
- Known hypersensitivity reaction to any ESA.
- Use of an investigational drug or treatment, participation in an investigational study, or presence of an expected carryover effect of an investigational treatment, within 4 weeks prior to randomization.
- Anticipated use of dapsone or androgens at any dose amount or chronic use of acetaminophen or paracetamol > 2.0 g/day during the study.
- History of alcohol or drug abuse within 6 months prior to randomization.
- Females of childbearing potential, unless using contraception as detailed in the protocol; male participants with sexual partners of childbearing potential who are not on birth control unless the male participant agrees to use contraception.
- Pregnant or breastfeeding females.
- Any medical condition that, in the opinion of the Investigator, may pose a safety risk to a participant in this study, may confound efficacy or safety assessment, or may interfere with study participation.
Trial locations and contacts
113 sites in 15 countries.
113 sites in 15 countries
United States30 sites
Investigational Site
Albuquerque, New Mexico, 87109
Investigational Site
Brookhaven, Mississippi, 39601
Investigational Site
Chula Vista, California, 91910
Investigational Site
Columbia, South Carolina, 29203
Investigational Site
Columbus, Mississippi, 39705
Investigational Site
Columbus, Ohio, 43215
Investigational Site
Coral Springs, Florida, 33071
Investigational Site
Detroit, Michigan, 48236
Investigational Site
Durham, North Carolina, 27704
Investigational Site
Edinburg, Texas, 78539
Investigational Site
Gulfport, Mississippi, 39501
Investigational Site
Houston, Texas, 77099
Investigational Site
Houston, Texas, 77450
Investigational Site
Knoxville, Tennessee, 37923
Investigational Site
La Mesa, California, 91942
Investigational Site
Lauderdale Lakes, Florida, 33313-1638
Meridian
Meridian, Idaho, 83642
Investigational Site
Miami, Florida, 33143
Investigational Site
Miami, Florida, 33173
Investigational Site
New Bern, North Carolina, 28562
Investigational Site
Orangeburg, South Carolina, 29118
Investigational Site
Pontiac, Michigan, 48341
Investigational Site
Portsmouth, New Hampshire, 38815
Investigational Site
Saint Ann, Missouri, 63074
Investigational Site
San Diego, California, 92111
Investigational Site
Shreveport, Louisiana, 71101
Investigational Site
St Louis, Missouri, 63136
Investigational Site
Sumter, South Carolina, 29150
Investigational Site
Tampa, Florida, 33614
Investigational Site
Tupelo, Mississippi, 38801
Russia21 sites
Investigational Site
Kaluga, Russian Federation, 248007
Investigational Site
Kolomna, 140407
Investigational Site
Krasnodar, Russian Federation, 350051
Investigational Site
Krasnodar, 350029
Investigational Site
Moscow, Russian Federation, 115446
Investigational Site
Moscow, Russian Ferderation, 125284
investigational Site
Moscow, 129327
Investigational Site
Nizhny Novgorod, Russian Federation, 603076
Investigational Site
Novorossiysk, 353915
Investigational site
Omsk, 644112
Investigational Site
Orenburg, 460040
Investigational Site
Petrozavodsk, Russian Federation, 185019
Investigational Site
Rostov-on-Don, 142100
Investigational Site
Saint Petersburg, Russian Federation, 191104
Investigational Site
Saint Petersburg, Russian Federation, 192242
Investigational Site
Saint Petersburg, Russian Federation, 193318
Investigational Site
Saint Petersburg, Russian Federation, 195257
Investigational Site
Saint Petersburg, 194354
Investigational site
Saint Petersburg, 196247
Investigational Site
Saint Petersburg, 197110
Investigational Site
Smolensk, Russian Federation, 214006
Bulgaria13 sites
Investigational Site
Burgas, 8000
Investigational site
Dobrich, 9300
Investigational site
Pazardzhik, 4400
Investigational site
Pernik, 2300
Investigational Site
Pleven, 5800
Investigational Site
Plovdiv, 4003
Investigational site
Rousse, 7000
Investigational Site
Sofia, 1233
Investigational Site
Sofia, 1407
Investigational site
Sofia, 1431
Investigational Site
Sofia, 1504
Invesigational Site
Stara Zagora, 6000
Investigational Site
Varna, 9000
Romania8 sites
Investigational Site
Bucharest, District 3, 031422
Investigational Site
Bucharest, 020475
Investigational Site
Bucharest, 022305
Investigational Site
Bucharest, 022325
Investigational Site
Bucharest, 022329
Investigational Site
Craiova, 200349
Investigational Site
Slatina, 230108
Investigational Site
Târgu Mureş, 540098
Ukraine7 sites
Investigational Site
Ivano, Frankivisk, 76008
Investigational Site
Karkiev, 61037
Investigational Site
Kiev, 02125
Investigational Site
Mykolayiv, 54058
Investigational Site
Ternopil, 46002
Investigational Site
Zaporizhzhya, 69118
Investigational Site
Zaporizhzhya, 69600
Malaysia6 sites
Investigational Site
Alor Star, 05460
Investigational Site
George Town, 10990
Investigational Site
Kuala Lumpur, 43000
Investigational Site
Kuala Lumpur, 50586
Investigational Site
Miri, Sarawak, 98000
Investigational Site
Taiping, 34000
South Korea6 sites
Investigational Site
Anyang-si, 431-796
Investigational site
Goyang-si, Gyeonggi-do, 410-719
Investigational Site
Guri-si, Gyeonggi-do, 471-701
Investigational Site
Seongnam-si, Gyeonggi-do, 463-712
Investigational Site
Seoul, 130-872
Investigational Site
Seoul, 134-727
Poland5 sites
Investigational Site
Chorzów, 41-500
Investigational Site
Golub-Dobrzyń, 87-400
Investigational Site
Inowrocław, 88-100
Investigational Site
Katowice, 40-027
Investigational Drug
Pruszków, 05-804
Taiwan4 sites
Investigational Site
Kaohsiung City, 83301
Investigational Site,
New Taipei City, 235
Investigational Site
Taichung, 40447
Investigational Site
Taichung, 433
Latvia3 sites
Investigational Site
Riga, LV-1038
Invetigational Site
Riga, LV1001
Investigational Site
Ventspils, LV3601
Argentina2 sites
Investigational Site
Santa Fe, IX Region, S3000EPU
Investigational Site
Serandi, Buenos Aires, 1872
Chile2 sites
Investigational Site
La Serena, Coquimbo Region, 1720421
Investigational Site
Temuco, Araucania, 4781151
Colombia2 sites
Investigational Site
Barranquilla, Atlántico
Investigational Site
Barranquilla
Mexico2 sites
Investigational Site
Aguascalientes, 20230
Investigational Site
San Luis Potosí City, 78240
Thailand2 sites
Investigational Site
Bangkok, 10330
Investigational Site
Chiang Mai, 50200
About this study
Official title: A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of the Efficacy and Safety of FG-4592 in the Treatment of Anemia in Incident-Dialysis Patients
The purpose of this study is to determine whether roxadustat is safe and effective in the treatment of anemia in participants who have just begun dialysis treatment for ESRD.
Read the detailed description
There is a screening period of up to 6 weeks, a treatment period of a minimum of 52 weeks and a maximum of approximately up to 3 years after last participant is randomized, and a post-treatment follow-up period of 4 weeks. Participants will be randomized in a 1:1 ratio to receive either open-label roxadustat or epoetin alfa (active control).
- Conditions
- Anemia in Incident Dialysis Patients
- Being tested
- Roxadustat, Epoetin Alfa
- Keywords
- Anemia, Chronic Kidney Disease, Hemoglobin, End-Stage Renal Disease, Incident-Dialysis, Erythropoieitin, Erythropoieisis stimulating-agent, Roxadustat, AZD9941, ASP1517, FG4592
- Medical subject headings
- Anemia, Renal Insufficiency, Chronic, Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RoxadustatDrug
Also called ASP1517, AZD9941, FG-4592
Roxadustat will be administered per dose and schedule specified in the arm.
Epoetin AlfaDrug
Also called Procrit, Epogen
Epoetin alfa will be administered TIW according to the epoetin alfa USPI or SmPC, or local SOC.
| Study group | Role | What they receive |
|---|---|---|
| Roxadustat | Experimental | Participants will receive roxadustat tablets, administered orally 3 times weekly (TIW). Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low weight [≤70 kilograms (kg)] and high weight [>70 to 160 kg] participants will receive 70 and 100 milligrams [mg] roxadustat, respectively). Dose adjustment to achieve correction and subsequent maintenance of target hemoglobin (Hb) values (10-12 grams [g]/deciliter [dL]) will be based upon regular monitoring of Hb. The maximum roxadustat dose is 3.0 mg/kg per dose or 400 mg per administration (whichever is lower). Receives: Drug: Roxadustat |
| Epoetin Alfa | Active comparator | Participants on hemodialysis (HD) will receive epoetin alfa, administered intravenously (IV) TIW, with starting doses and dose adjustment rules as per United States Package Insert (USPI) or summary of product characteristics (SmPC). Participants on home HD or peritoneal dialysis (PD) will receive epoetin alfa, administered subcutaneously (SC) as per the country-specific product label (USPI or SmPC) or local standard of care (SOC). Receives: Drug: Epoetin Alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 52), Regardless of Rescue Therapy (ITT Population)
Hb values under the influence of rescue therapy were not censored for the primary analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (erythropoiesis-stimulating agent [ESA]) or red blood cell (RBC) transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment. The intermittent missing Hb data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model, Monotone missing data were imputed by regression from its own treatment group.
Measured: Baseline (Day 1, Week 0), Week 28 to 52
Ex-U.S. Submission: Hb Responder Rate- Percentage of Participants Who Achieved a Hb Response at 2 Consecutive Visits at Least 5 Days Apart During First 24 Weeks of Treatment, Without Rescue Therapy Within 6 Weeks Prior to the Hb Response (PPS Population)
Hb response was defined, using central laboratory values, as: Hb ≥11.0 g/dL and a Hb increase from baseline by ≥1.0 g/dL in participants whose baseline Hb >8.0 g/dL, or increase in Hb ≥2.0 g/dL in participants whose baseline Hb ≤8.0 g/dL. Rescue therapy for roxadustat treated participant was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion.
Measured: Baseline (Day 1, Week 0) up to Week 24
Secondary outcomes (12)
US (FDA Submission): Hb Responder Rate- Percentage of Participants Who Achieved a Hb Response at 2 Consecutive Visits at Least 5 Days Apart During First 24 Weeks of Treatment, Without Rescue Therapy Within 6 Weeks Prior to the Hb Response (ITT Population)
Hb response was defined, using central laboratory values, as: Hb ≥11.0 g/dL and a Hb increase from baseline by ≥1.0 g/dL in participants whose baseline Hb >8.0 g/dL, or increase in Hb ≥2.0 g/dL in participants whose baseline Hb ≤8.0 g/dL. Rescue therapy for roxadustat treated participant was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion.
Measured: Baseline (Day 1, Week 0) up to Week 24
Ex-US Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 52), Regardless of Rescue Therapy (PPS Population)
Hb values under the influence of rescue therapy were censored up to 6 weeks in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment. The intermittent missing Hb data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the MCMC imputation model, Monotone missing data were imputed by regression from its own treatment group.
Measured: Baseline (Day 1, Week 0), Week 28 to 52
Mean Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 24
Baseline LDL Cholesterol was defined as the mean of values obtained within 6 weeks prior to the first dose of study treatment.
Measured: Baseline (Day 1, Week 0), Week 12 to 24
Mean Change From Baseline in Hb Levels Between Weeks 18 to 24 Regardless of Rescue Therapy in Participants Whose Baseline High Sensitivity C-Reactive Protein (Hs-CRP)> Upper Limit of Normal (ULN)
Hb values under the influence of rescue therapy were not censored in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment. The intermittent missing Hb data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the MCMC imputation model, Monotone missing data were imputed by regression from its own treatment group.
Measured: Baseline (Day 1, Week 0), Week 18 to 24
Median Monthly IV Iron Use Per Patient-Exposure-Month (PEM) During Weeks 28 to 52
Monthly iron use for each participant = Total IV iron in mg / [(last dose date - first dose date of study medication in the period)+1]/ 28.
Measured: Weeks 28 to 52
Time to First RBC Transfusion
Median time to event (weeks) was calculated using Kaplan Meier Survival Estimates.
Measured: Baseline (Day 1, Week 0) up to last dose of study drug (maximum treatment duration was 227.9 weeks for roxadustat and 226.9 weeks for epoetin alfa)
Mean Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 8 to 12
Baseline MAP was defined as the last MAP value prior to the first dose of study treatment.
Measured: Baseline (Day 1, Week 0), Weeks 8 to 12
Time to First Exacerbation of Hypertension During Weeks 28 to 52
An exacerbation of hypertension was defined as increase from baseline of ≥20 mmHg in systolic blood pressure (sBP) and sBP ≥170 mmHg or an increase from baseline of ≥15 mm Hg in diastolic blood pressure (dBP) and dBP ≥100 mmHg. Median time to event (weeks) was calculated using Kaplan Meier Survival Estimates.
Measured: Weeks 28 to 52
Percentage of Participants With Exacerbation of Hypertension During Weeks 28 to 52
Percentage of participants with exacerbation of hypertension, meeting at least one of the following criteria are reported: i) Increase in BP: An increase from baseline of ≥ 20 mmHg in sBP and sBP >170 mmHg, or an increase from baseline of ≥15 mmHg dBP and dBP >100 mmHg.
Measured: Weeks 28 to 52
Time to Achieve the First Hb Response up to Week 24 Censoring for Rescue Therapy
Hb values under the influence of rescue therapy were censored up to 6 weeks in the analysis. Hb response was defined, using central laboratory values, as: Hb ≥11.0 g/dL and a Hb increase from baseline by ≥1.0 g/dL in participants whose baseline Hb >8.0 g/dL, or increase in Hb ≥2.0 g/dL in participants whose baseline Hb ≤8.0 g/dL. Rescue therapy for roxadustat treated participant was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Median time to event was calculated using Kaplan Meier Survival Estimates.
Measured: Baseline (Day 1, Week 0) up to Week 24
Percentage of Participants With Hb ≥10.0 g/dL Averaged Over Weeks 28 to 36 and 28 to 52, Regardless of Rescue Therapy
Hb values under the influence of rescue therapy were not censored in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment.
Measured: Weeks 28 to 36 and 28 to 52
Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 36), Censoring for Rescue Therapy
Hb values under the influence of rescue therapy were censored up to 6 weeks in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment.
Measured: Baseline (Day 1, Week 0), Week 28 to 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2014 (estimated)
- Study start11 Feb 2014
- Primary completion21 Sep 2018
- Study completion21 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 (3)Papers the sponsor has linked to this study.
- Other trials for Anemia in Incident Dialysis PatientsStudies of the same condition, open and under way.
- 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
- 1,043 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyntra Bio
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Astellas Pharma Europe B.V., AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Charles Bradley, PhD, Study director, Kyntra Bio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02052310
- Sponsor's protocol ID
- FGCL-4592-063
- Other IDs
- 2013-002753-30
- Acronym
- Himalayas
- Status last verified
- Sep 2021
- First submitted
- 6 Jan 2014
- Last updated
- 1 Oct 2021
- 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 36005278
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2021. 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 Efficacy and Safety of FG-4592 in the Treatment of Anemia in Incident-Dialysis Patients
- ClinicalTrials.gov ID
- NCT02052310
- Acronym / sponsor ID
- Himalayas / FGCL-4592-063
- Conditions
- Anemia in Incident Dialysis Patients
- Keywords
- Anemia, Chronic Kidney Disease, Hemoglobin, End-Stage Renal Disease, Incident-Dialysis, Erythropoieitin, Erythropoieisis stimulating-agent, Roxadustat
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,043 participants (actual)
- Lead sponsor
- Kyntra BioIndustry (pharma, biotech, devices)
- Collaborators
- Astellas Pharma Europe B.V., AstraZeneca
- Study start
- 11 Feb 2014 (actual)
- Primary completion
- 21 Sep 2018 (actual)
- Study completion
- 21 Sep 2018 (actual)
- First posted
- 3 Feb 2014 (estimated)
- Results
- Posted 1 Oct 2021
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 determine whether roxadustat is safe and effective in the treatment of anemia in participants who have just begun dialysis treatment for ESRD.
Detailed description
There is a screening period of up to 6 weeks, a treatment period of a minimum of 52 weeks and a maximum of approximately up to 3 years after last participant is randomized, and a post-treatment follow-up period of 4 weeks. Participants will be randomized in a 1:1 ratio to receive either open-label roxadustat or epoetin alfa (active control).
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: RoxadustatParticipants will receive roxadustat tablets, administered orally 3 times weekly (TIW). Initial roxadustat dose will be based on a tiered, weight-based dosing scheme (low weight [≤70 kilograms (kg)] and high weight [>70 to 160 kg] participants will receive 70 and 100 milligrams [mg] roxadustat, respectively). Dose adjustment to achieve correction and subsequent maintenance of target hemoglobin (Hb) values (10-12 grams [g]/deciliter [dL]) will be based upon regular monitoring of Hb. The maximum roxadustat dose is 3.0 mg/kg per dose or 400 mg per administration (whichever is lower). |
| Epoetin Alfa | Active comparator | Drug: Epoetin AlfaParticipants on hemodialysis (HD) will receive epoetin alfa, administered intravenously (IV) TIW, with starting doses and dose adjustment rules as per United States Package Insert (USPI) or summary of product characteristics (SmPC). Participants on home HD or peritoneal dialysis (PD) will receive epoetin alfa, administered subcutaneously (SC) as per the country-specific product label (USPI or SmPC) or local standard of care (SOC). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Participant has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines.
- Receiving HD or PD for ESRD for a minimum of 2 weeks and a maximum of 4 months, prior to randomization.
- Hemodialysis access consisting of an arteriovenous (AV) fistula, AV graft, or tunnelled (permanent) catheter; or PD catheter in use.
- Mean of the two most recent predialysis Hb values during the Screening Period, obtained at least 2 days apart, must be ≤ 10.0 g/dL, with a difference of ≤ 1.3 g/dL between the highest and the lowest values. The last Hb value must be drawn within 10 days prior to randomization.
- Ferritin ≥ 100 nanograms (ng)/milliliter (mL) (≥ 220 picomoles (pmol)/L); participants with ferritin level < 100 ng/mL(<220 pmol/L) during screening, qualify after receiving iron supplement (per local standard of care), without the need to retest ferritin prior to randomization.
Key exclusion criteria (33 listed)
- Total duration of prior effective ESA use must be ≤3 weeks within the preceding 12 weeks at the time informed consent is obtained.
- Specific dosing guidance, depending on the type of ESAs, injected IV or SC within 12 weeks prior to start of screening are as follows:
- Short-acting ESAs (EPO-alfa or equivalents) - IV: Up to 9 doses, last EPO dose must be ≥2 days prior to start of screening; SC: Up to 3 doses, last EPO dose must be ≥1 week (7 days) prior to start of screening ii) Darbepoetin - IV: Up to 3 doses, last darbepoetin dose must be ≥1 week (7 days) prior to start of screening; SC: Up to 2 doses, last darbepoetin dose must be ≥2 weeks (14 days) prior to start of screening iii) Continuous erythropoietin receptor activator (CERA) IV and SC: Up to 2 doses; last CERA dose must be ≥2 weeks (14 days) prior to start of screening
- Intravenous iron: there is no restriction regarding IV iron use during screening, provided it is administered in accordance with local SOC.
- Red blood cell transfusion within 4 weeks prior to randomization.
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 |
|---|---|---|
| RoxadustatAlso: ASP1517, AZD9941, FG-4592Roxadustat will be administered per dose and schedule specified in the arm. | Drug | Roxadustat |
| Epoetin AlfaAlso: Procrit, EpogenEpoetin alfa will be administered TIW according to the epoetin alfa USPI or SmPC, or local SOC. | Drug | Epoetin Alfa |
Primary outcome
US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 52), Regardless of Rescue Therapy (ITT Population)
Time frame: Baseline (Day 1, Week 0), Week 28 to 52
Hb values under the influence of rescue therapy were not censored for the primary analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (erythropoiesis-stimulating agent [ESA]) or red blood cell (RBC) transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment. The intermittent missing Hb data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model, Monotone missing data were imputed by regression from its own treatment group.
Ex-U.S. Submission: Hb Responder Rate- Percentage of Participants Who Achieved a Hb Response at 2 Consecutive Visits at Least 5 Days Apart During First 24 Weeks of Treatment, Without Rescue Therapy Within 6 Weeks Prior to the Hb Response (PPS Population)
Time frame: Baseline (Day 1, Week 0) up to Week 24
Hb response was defined, using central laboratory values, as: Hb ≥11.0 g/dL and a Hb increase from baseline by ≥1.0 g/dL in participants whose baseline Hb >8.0 g/dL, or increase in Hb ≥2.0 g/dL in participants whose baseline Hb ≤8.0 g/dL. Rescue therapy for roxadustat treated participant was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion.
12 secondary outcomes
US (FDA Submission): Hb Responder Rate- Percentage of Participants Who Achieved a Hb Response at 2 Consecutive Visits at Least 5 Days Apart During First 24 Weeks of Treatment, Without Rescue Therapy Within 6 Weeks Prior to the Hb Response (ITT Population)
Time frame: Baseline (Day 1, Week 0) up to Week 24
Ex-US Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 52), Regardless of Rescue Therapy (PPS Population)
Time frame: Baseline (Day 1, Week 0), Week 28 to 52
Mean Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 24
Time frame: Baseline (Day 1, Week 0), Week 12 to 24
Mean Change From Baseline in Hb Levels Between Weeks 18 to 24 Regardless of Rescue Therapy in Participants Whose Baseline High Sensitivity C-Reactive Protein (Hs-CRP)> Upper Limit of Normal (ULN)
Time frame: Baseline (Day 1, Week 0), Week 18 to 24
Median Monthly IV Iron Use Per Patient-Exposure-Month (PEM) During Weeks 28 to 52
Time frame: Weeks 28 to 52
Time to First RBC Transfusion
Time frame: Baseline (Day 1, Week 0) up to last dose of study drug (maximum treatment duration was 227.9 weeks for roxadustat and 226.9 weeks for epoetin alfa)
Mean Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 8 to 12
Time frame: Baseline (Day 1, Week 0), Weeks 8 to 12
Time to First Exacerbation of Hypertension During Weeks 28 to 52
Time frame: Weeks 28 to 52
Percentage of Participants With Exacerbation of Hypertension During Weeks 28 to 52
Time frame: Weeks 28 to 52
Time to Achieve the First Hb Response up to Week 24 Censoring for Rescue Therapy
Time frame: Baseline (Day 1, Week 0) up to Week 24
Percentage of Participants With Hb ≥10.0 g/dL Averaged Over Weeks 28 to 36 and 28 to 52, Regardless of Rescue Therapy
Time frame: Weeks 28 to 36 and 28 to 52
Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 36), Censoring for Rescue Therapy
Time frame: Baseline (Day 1, Week 0), Week 28 to 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2021.
- 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.
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.
Charles Bradley, PhD study director
Kyntra Bio
113 sites in 15 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 in Incident Dialysis Patients, run by Kyntra Bio at 113 sites in 15 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 10 inclusion and 33 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 1 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 113 sites in United States, Russia, Bulgaria, Romania, Ukraine and 10 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 1 Oct 2021). 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?
US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 52), Regardless of Rescue Therapy (ITT Population) (time frame: Baseline (Day 1, Week 0), Week 28 to 52). The study lists 2 primary outcomes in all. 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 NCT02052310, which also lists 3 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 1 Oct 2021.