| Eligibility |
Inclusion Criteria:
Informed consent • Provision of signed and dated, written informed consent form (ICF) prior
to any mandatory study specific procedures, sampling, and analyses.
Type of patient and disease characteristics
At Visit 1 prior to screening
Dialysis patients:
- Patients receiving hemodialysis (HD) or peritoneal dialysis (PD) for treatment of
end-stage renal disease (ESRD) for at least 12 weeks. Patients treated with HD must
have access consisting of an arteriovenous (AV) fistula, AV graft, or tunneled
(permanent) catheter. Patients on PD must have a functioning PD catheter in place.
- Hemodialysis patients should be on 3x/week dialysis with evidence of achievement of
adequate dialysis as defined by standardized Kt/V =2.1 in HD, and total (renal + PD)
weekly Kt/V =1.7 in PD documented twice during the 16 weeks preceding screening for
the study.
- Patients should be on a stable rHuEPO dose as defined by change in rHuEPO dose, not
exceeding 20% within 4 weeks prior to screening.
Non-dialysis patients:
- Patients with estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m^2,
corresponding to Stage 4 or Stage 5 CKD according to the Kidney Disease Outcomes
Quality Initiative (KDOQI), and not receiving dialysis.
- Patients should either be on a stable dose of rHuEPO for 4 weeks before screening or
be rHuEPO-naïve.
Dialysis and non-dialysis patients:
• Patients agree not to take any new traditional Chinese medicine (TCM) and not to change,
dose, schedule or brand of any TCM from beginning of the Screening Period through the end
of the Follow-up Period.
At Visit 1 (screening)
- Ferritin =50 ng/mL and transferrin saturation (TSAT) =15% in non-dialysis patients
- Ferritin =100 ng/mL and TSAT =20% in dialysis patients.
- Dry body weight should be 45 to 100 kg.
During the Screening Period:
- Dialysis patients must have a mean Hb level of = 9 to = 12 g/dL based on the mean of
the 2 most recent central laboratory Hb values within 0.50 g/dL on 2 assays taken at
least 7 days apart during the Screening Period.
- Non-dialysis patients must have a mean Hb level of = 9 to = 12 g/dL for rHuEPO-user
patients and = 7 and = 10 g/dL for rHuEPO-naïve patients, based on the mean of the 2
most recent central laboratory Hb values within 0.50 g/dL on 2 assays taken at least 7
days apart during the Screening Period.
At Visit 1 Screening:
- Serum folate level = lower limit of normal (LLN).
- Serum vitamin B12 level = LLN.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 3 x ULN and total
bilirubin (TBL) = 1.5 x ULN.
- Negative test results on the swab test to rule out active COVID-19 infection. If
according to site procedures the test for COVID-19 infection cannot be performed at
the first Screening Visit, the test should be performed as soon as possible thereafter
but must be performed before the patient returns for the next study visit. Any patient
who has had confirmed COVID-19 infection in the past, has fully recovered from
symptoms at least 14 days prior to Screening, and has a negative swab test result for
COVID-19 infection at Screening, may be included in the study.
Reproduction:
- Serum pregnancy test should be negative for female of childbearing potential at the
start of the Screening Period.
- Female patients of childbearing potential and male patients (non-surgically sterile)
with a female partner of childbearing potential must, if not practicing complete
sexual abstinence, agree to practice a dual method of contraception.
Contraceptive methods must be practiced upon being randomized to the study and through 7
days after the last dose of study treatment. Male patients must not donate or bank sperm
during this same time period.
Exclusion Criteria:
Medical conditions
- New York Heart Association Class III or IV congestive heart failure (CHF) at
screening.
- Acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (eg,
deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
- History of severe, chronic, end-stage, or uncontrolled autoimmune liver disease with
ALT 3 x ULN, or AST > 3 × ULN, or total bilirubin > 1.5 × ULN.
- 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.
- Systolic BP =160 mmHg or diastolic BP =95 mmHg (confirmed by repeated measurement),
within 2 weeks prior to randomization. Patients may be rescreened once BP is
controlled.
- History of prostate cancer, breast cancer, renal cell carcinoma 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.
- Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus
erythromatosus (SLE), ankylosing spondylitis, psoriatic arthritis or active
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 current condition leading to active significant blood loss.
- Known allergy to the study treatment 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.
- Intolerance of oral iron in the past as defined by stomach upset, nausea, vomiting, or
diarrhea.
- Active GI bleed.
- Hospitalizations within the 12 weeks preceding study randomization for GI bleeding or
Congestive heart failure.
- Life expectancy <6 months.
- Patients who are likely to be initiated on dialysis within the next 3 months per
Investigator's assessment at the time of screening.
- Previous bowel resection.
- Coeliac disease.
- Gastroenteritis in the 4 weeks prior to randomization.
- Cognitive disabilities, physical or psychiatric disease that in the opinion of the
Investigator/clinician influence the patient's adherence and successful completion of
the study.
Prior/concomitant therapy:
- Any treatment with roxadustat or a Hypoxia-Inducible Factor Prolyl Hydroxylase
Inhibitors (HIF-PHI).
- Any red blood cells transfusion within 6 weeks prior to the first Screening Visit, or
during the Screening Period.
- Has received another new chemical entity (defined as a compound which has not been
approved for marketing) within the 12 weeks prior to Screening Visit.
- Exposure to IV iron or use of TRIFERIC® in dialysate during the Screening Period (ie,
2 weeks before randomization [Day 1]).
- Exposure to iron-chelating agent (eg, deferoxamine/desferrioxamine, deferiprone or
deferaxirox therapy) within the 6 weeks prior to the first Screening Visit.
Prior/concurrent clinical study experience:
• Participation in any other clinical study that included drug treatment within at least 4
weeks of screening.
Other exclusions:
- Involvement in the planning and/or conduct of the study (applies to AstraZeneca and
FibroGen staff and/or staff at the study site).
- Patient non-adherence to medications or missing >1 dialysis treatments/month per the
Investigator's knowledge.
- Previous randomization in the present study.
- History of alcohol or drug abuse within 2 years prior to randomization.
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