A Study to Investigate the Effect of Roxadustat Versus Recombinant Human Erythropoietin (rHuEPO) on Oral Iron Absorption in Chinese Patients With Anemia of Chronic Kidney Disease (CKD)

NCT04655027 | Completed Phase 4 Results

• 1 other identifier: D5741C00002
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 8

Brief Summary

This is a Phase IV, randomized, active-controlled, open-label, parallel design, multicenter prospective study to evaluate the effect of roxadustat versus rHuEPO treatment on the gastrointestinal (GI) iron absorption in patients with anemia of Stage 4 and Stage 5 CKD.

Conditions

Anemia of Chronic Kidney Disease

Keywords

Recombinant Human Erythropoietin; Roxadustat; Coronavirus disease of 2019; Chronic kidney disease; Anemia

Outcome Measures

Primary Outcomes (1)

• Difference From Baseline to Day 15 in Area Under Curve (AUC) of GI Iron Absorption (0-3 Hours)

  The main effect of roxadustat versus rHuEPO on GI iron absorption was evaluated.

  From Baseline (Day 1) to Day 15

Secondary Outcomes (9)

• Difference From Baseline to Day 15 in Area Under Curve (AUC) of Iron Absorption (0-3 Hours)

  From Baseline (Day 1) to Day 15

• Difference From Baseline to Day 15 in Serum Iron

  From baseline (Day 1) to Day 15

• Difference From Baseline to Day 15 in Ferritin

  From baseline (Day 1) to Day 15

• Difference From Baseline to Day 15 in Total Iron Binding Capacity (TIBC)

  From baseline (Day 1) to Day 15

• Relative Difference From Baseline to Day 15 in Transferrin Saturation (TSAT)

  From baseline (Day 1) to Day 15

Study Arms (2)

Roxadustat

EXPERIMENTAL

Patients will receive oral dose of roxadustat three times a week (TIW) for 2- weeks during treatment period.

Drug: Roxadustat

rHuEPO

ACTIVE COMPARATOR

Patients will receive uniform brand of short acting intravenous or subcutaneous dose of rHuEPO two times a week (BIW) or TIW based upon their previous dose of rHuEPO for 2- weeks during treatment period.

Drug: rHuEPO

Interventions

Roxadustat DRUG

The starting dose of roxadustat will be in accordance with the China package insert, and will depend on the body weight of the patient: 100 mg (45 to \< 60 kg) or 120 mg (≥ 60 kg) in patients on dialysis; 70 mg (40 to \< 60 kg) or 100 mg (≥ 60 kg) in non-dialysis patients.

Roxadustat

rHuEPO DRUG

The starting dose of rHuEPO will be in accordance to the dosage approved in rHuEPO China package insert (patients on weekly dose of 6000 IU \[dosing will BIW\], and patients on weekly dose of \>6000 IU \[dosing will TIW\]) and on patient's haemoglobin levels.

rHuEPO

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (8)

Research Site

Baotou, 14010, China

Location

Research Site

Beijing, 100029, China

Location

Research Site

Beijing, 100044, China

Location

Research Site

Beijing, 100730, China

Location

Research Site

Guangzhou, 510180, China

Location

Research Site

Jinan, 250012, China

Location

Research Site

Shenyang, 110001, China

Location

Research Site

Wuhan, 430022, China

Location

Related Publications (1)

• Wu H, Cheng H, Wang C, Yao L, Qin S, Zuo L, Hu Z, Zhang C, Wu Y, Hofherr A, Mohan K, Rush S, Li X. Roxadustat and Oral Iron Absorption in Chinese Patients with Anemia of Chronic Kidney Disease: A Randomized, Open-Label, Phase 4 Study (ALTAI). Adv Ther. 2024 Mar;41(3):1168-1183. doi: 10.1007/s12325-023-02741-5. Epub 2024 Jan 27.

  PMID: 38280066 DERIVED

Related Links

• redacted Statistical Analysis Plan
• redacted Clinical Study Protocol
• redacted Clinical Study Report Synopsis

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Anemia

Interventions

roxadustat

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

* NDD randomization strata were merged because recruitment was insufficient. * The log-transform of AUC was removed from the primary assessment post-database-lock when negative AUC were discovered (which invalidated log-transformation).

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical study Information Center

information.center@astrazeneca.com

1-877-240-94 79

Study Officials

• Li Xuemei

  Peking Union Medical College Hospital (Dongdan campus) No.1 Shuaifuyuan Wangfujing Dongcheng District Beijing, China 100730

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 4, 2020
• Study Start: February 22, 2021
• Primary Completion: October 12, 2021
• Study Completion: October 12, 2021
• Last Updated: April 22, 2024
• Results First Posted: April 22, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

CN (8)