Safety and Efficacy Study for Treatment of Anemia in ESRD Newly Initiated Dialysis Patients (Himalayas)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by FibroGen
Sponsor:
Collaborators:
Astellas Pharma Europe B.V.
AstraZeneca
Information provided by (Responsible Party):
FibroGen
ClinicalTrials.gov Identifier:
NCT02052310
First received: January 6, 2014
Last updated: March 24, 2015
Last verified: March 2015
  Purpose

The purpose of this study is to determine whether FG-4592 (roxadustat) is safe and effective in the treatment of anemia in patients who have just begun dialysis treatment for end stage renal disease.


Condition Intervention Phase
Anemia in Incident Dialysis Patients
Drug: FG-4592 (roxadustat)
Drug: Epoetin Alfa
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 3, Multicenter, Randomized, Open-Label,Active-Controlled Study of the Efficacy and Safety of FG-4592 (Roxadustat) in the Treatment of Anemia in Incident-Dialysis Patients

Resource links provided by NLM:


Further study details as provided by FibroGen:

Primary Outcome Measures:
  • U.S.A.: Mean Hemoglobin (Hb) change from baseline to average levels from Week 28 to Week 52. Ex-U.S.A.: Proportion of subjects who achieve a Hb response during the first 24 weeks of treatment. [ Time Frame: Minimum of 52 weeks and maximum of up to 3 years after last subject is randomized. ] [ Designated as safety issue: No ]

    A Hb response is defined as:

    Hb ≥11.0g/dL and a Hb increase from baseline by ≥1.0g/dL in subjects whose baseline Hb >8.0g/dL, or Increase in Hb ≥2.0g/dL in subjects whose baseline Hb ≤8.0g/dL.



Secondary Outcome Measures:
  • U.S.A.: Proportion of subjects who achieve a Hemoglobin (Hb) response during the first 24 weeks of treatment. Ex-U.S.A.: Mean Hb change from baseline to average levels from Week 28 to Week 52. [ Time Frame: Varies based on Ex-U.S.A. vs. U.S.A. submission ] [ Designated as safety issue: No ]

    A Hb response is defined as:

    Hb ≥11.0g/dL and a Hb increase from baseline by ≥1.0g/dL in subjects whose baseline Hb >8.0g/dL, or

    Increase in Hb ≥2.0g/dL in subjects whose baseline Hb ≤8.0g/dL.


  • Use of Iron [ Time Frame: week 0 -End of Treatment ] [ Designated as safety issue: No ]
    Average monthly IV iron use per subject during the Treatment Period.

  • Serum lipid parameters [ Time Frame: Weeks 12-24 ] [ Designated as safety issue: No ]
    Mean change in low-density lipoprotein (LDL) cholesterol.

  • Blood pressure effects [ Time Frame: Treatment Period; Weeks 8-12 ] [ Designated as safety issue: Yes ]

    Proportions of patients with exacerbation of hypertension, meeting at least one of the following criteria:

    • An increase from baseline in sBP of ≥ 20 mm Hg and sBP >170 mmHg, or
    • An increase from baseline in dBP of ≥ 15 mm Hg and dBP>100 mmHg. Increases in blood pressure must be confirmed by repeat measurement. Time to an increase in blood pressure as defined above Mean change in mean arterial pressure (MAP) averaged over Weeks 8-12.

  • Time to achieve Hemoglobin (Hb) response [ Time Frame: Varies based on U.S.A. vs. Ex-U.S.A. submission ] [ Designated as safety issue: No ]
    Time to achieve first Hb response as defined by the primary endpoint (ex-U.S.A.) and secondary endpoint (U.S.A).


Other Outcome Measures:
  • Health-related quality of life (HRQoL) [ Time Frame: Weeks 12, 36, 52 and EOT ] [ Designated as safety issue: No ]
    Health-related quality of life (HRQoL) will be assessed using the SF-36 FACT-AN and EQ-5D-5L questionnaires

  • Additional efficacy analysis [ Time Frame: Treatment weeks up to EOT ] [ Designated as safety issue: No ]
    Hemoglobin maintenance, rescue therapy, hospitalizations, other additional labs of interest.


Estimated Enrollment: 750
Study Start Date: December 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FG-4592 (roxadustat)
FG-4592 (roxadustat) will be dosed orally three times a week.
Drug: FG-4592 (roxadustat)
Drug will be dosed orally three times a week.
Other Names:
  • ASP1517
  • AZD9941
Active Comparator: Epoetin alfa
Epoetin alfa will be dispensed per the package insert or the country-specific product labeling.
Drug: Epoetin Alfa
The drug will be dispensed per the package insert or the country-specific product labeling.
Other Name: Procrit, Epogen

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 patient is randomized, and a post-treatment follow-up period of 4 weeks. A total of up to 750 patients, will be randomized in a 1:1 ratio (375 roxadustat and 375 epoetin alfa) to receive either open-label FG-4592 (roxadustat) or Active Control (Epoetin alfa).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 years.
  2. Receiving hemodialysis or peritoneal dialysis for end-stage renal disease for a minimum of 2 weeks and a maximum of 4 months, prior to study participation.
  3. Study participant has permanent dialysis access in place.
  4. No iron deficiency.
  5. No folate or Vitamin B12 deficiency.
  6. No abnormal liver tests.
  7. Body weight up to 160 kg (HD: dry weight).

Note: Blood tests will be conducted to determine whether or not study participant has anemia, and meets all eligibility criteria.

Exclusion Criteria:

  1. Any erythropoieisis-stimulating agent treatment within 12 weeks prior to participating in the study.
  2. Intravenous iron within 10 days prior to participating in the study.
  3. Red blood cell transfusion within 8 weeks prior to participating in the study.
  4. Active infection.
  5. Chronic liver disease (e.g., chronic infectious hepatitis, chronic auto-immune liver disease, cirrhosis, or fibrosis of the liver).
  6. Congestive heart failure.
  7. Heart attack, stroke, or blood-clots within a major vessel within 12 weeks prior to participating in the study.
  8. Uncontrolled high blood pressure within 2 weeks prior to participating in the study.
  9. Renal ultrasound performed within 12 weeks prior to participating in the study suspicious of renal cancer.
  10. Active cancer.
  11. Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
  12. Chronic inflammatory disease that could cause anemia.
  13. Known and untreated damage to the retina from diabetes.
  14. Known history of blood-related diseases causing anemia, or blood-related cancer.
  15. Known inherited disease such as thalassemia or sickle cell anemia or other known causes for anemia other than chronic kidney disease.
  16. Known clotting disorders and iron storage disorders.
  17. Any prior organ transplant (that has not been explanted), or a scheduled organ transplantation.
  18. Anticipated surgery that is expected to cause blood loss.
  19. Known gastrointestinal bleeding.
  20. Any prior treatment with FG-4592 (roxadustat) or a hypoxia-inducible factor prolyl hydroxylase inhibitor.
  21. Use of iron-binding medications within 4 weeks prior to participating in the study.
  22. Known allergies to any erythropoieisis-stimulating agent.
  23. 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 participating in the study.
  24. Anticipated use of dapsone or androgens at any dose amount or chronic use of acetaminophen or paracetamol >2.0 g/day during the study.
  25. History of alcohol or drug abuse within 2 years prior to participating in the study.
  26. Women who can become pregnant must use contraception. Men with sexual partners who can become pregnant must use birth control, unless the man agrees to use contraception.
  27. Pregnant or breastfeeding women.
  28. Any medical condition, that in the opinion of the study doctor, may pose a safety risk to the patient, may confound efficacy or safety assessment, or may interfere with study participation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02052310

Contacts
Contact: Trial Coordinator 415-978-1200 ext 1672 063study@fibrogen.com

  Show 150 Study Locations
Sponsors and Collaborators
FibroGen
Astellas Pharma Europe B.V.
AstraZeneca
Investigators
Study Director: Charles Bradley, PhD FibroGen
  More Information

No publications provided

Responsible Party: FibroGen
ClinicalTrials.gov Identifier: NCT02052310     History of Changes
Other Study ID Numbers: FGCL-4592-063, 2013-002753-30
Study First Received: January 6, 2014
Last Updated: March 24, 2015
Health Authority: United States: Food and Drug Administration
Russia: Ministry of Health of the Russian Federation
Ukraine: Ministry of Health
Estonia: The State Agency of Medicine
Belarus: Ministry of Health
Bulgaria: Bulgarian Drug Agency
Poland: The Central Register of Clinical Trials
Malaysia: Ministry of Health
Taiwan : Food and Drug Administration
South Korea: Korea Food and Drug Administration (KFDA)
Hong Kong: Department of Health
Thailand: Food and Drug Administration
Romania: Ministry of Public Health
Latvia: State Agency of Medicines
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Chile: Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Peru: Ministry of Health
Brazil: Ministry of Health
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos

Keywords provided by FibroGen:
Anemia
Chronic Kidney Disease
Hemoglobin
End-Stage Renal Disease
Incident-Dialysis
Erythropoieitin
Erythropoieisis stimulating-agent
Roxadustat
AZD9941
ASP1517

Additional relevant MeSH terms:
Anemia
Hematologic Diseases
Epoetin alfa
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 27, 2015