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

January 6, 2014
March 24, 2015
December 2013
June 2017   (final data collection date for primary outcome measure)
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.

Hemoglobin response to treatment using various FG-4592 dosing regimens. [ Time Frame: Change from Baseline hemoglobin to 24 weeks ] [ Designated as safety issue: No ]
Cumulative number (%) of subjects with hemoglobin greater than or equal to 11g/dL and increase of greater than or equal to 1 g/dL from baseline up to 24 weeks.
Complete list of historical versions of study NCT02052310 on ClinicalTrials.gov Archive Site
  • 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).
  • Hemoglobin maintenance once correction is achieved. [ Time Frame: Week 28-36 ] [ Designated as safety issue: No ]
    Mean change in Hb averaged over 8 weeks of treatment at Weeks 28-36, without rescue therapy within 6 weeks prior to and during this 8 week evaluation period.
  • Average monthly IV iron use per subject [ Time Frame: Weeks 1 up to 156 weeks. ] [ Designated as safety issue: No ]
    Average monthly IV iron use per subject
  • Mean change in low-density lipoprotein (LDL) cholesterol [ Time Frame: Weeks 12-24 ] [ Designated as safety issue: No ]
  • Cumulative number (%) of patients with with exacerbation of hypertension. [ Time Frame: Change in blood pressure from baseline up to weeks 156. ] [ Designated as safety issue: Yes ]
    At least one of the following criteria must be met in order to be considered an exacerbation of hypertension: an increase in anti-hypertensive medication use; an adverse event of hypertension or an increase in blood-pressure from baseline confirmed by repeat measurement.
  • Time to achieve Hemoglobin response [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
    Time to achieve first Hb response as defined by the primary endpoint.
  • Change in the Health-related quality of life (HRQoL) [ Time Frame: Weeks 12, 28 and 52. ] [ Designated as safety issue: No ]
    Health-related quality of life (HRQoL) will be assessed using the SF-36, vitality and physical functioning subscales. Both within-treatment and between-treatment effect will be assessed.
  • 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.
Not Provided
 
Safety and Efficacy Study for Treatment of Anemia in ESRD Newly Initiated Dialysis Patients
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

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.

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).

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Anemia in Incident Dialysis Patients
  • Drug: FG-4592 (roxadustat)
    Drug will be dosed orally three times a week.
    Other Names:
    • ASP1517
    • AZD9941
  • Drug: Epoetin Alfa
    The drug will be dispensed per the package insert or the country-specific product labeling.
    Other Name: Procrit, Epogen
  • Experimental: FG-4592 (roxadustat)
    FG-4592 (roxadustat) will be dosed orally three times a week.
    Intervention: Drug: FG-4592 (roxadustat)
  • Active Comparator: Epoetin alfa
    Epoetin alfa will be dispensed per the package insert or the country-specific product labeling.
    Intervention: Drug: Epoetin Alfa
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
750
June 2017
June 2017   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Trial Coordinator 415-978-1200 ext 1672 063study@fibrogen.com
United States,   Argentina,   Belarus,   Bulgaria,   Chile,   Colombia,   Estonia,   Korea, Republic of,   Latvia,   Malaysia,   Mexico,   Poland,   Romania,   Russian Federation,   Taiwan,   Thailand,   Ukraine
 
NCT02052310
FGCL-4592-063, 2013-002753-30
Yes
FibroGen
FibroGen
  • Astellas Pharma Europe B.V.
  • AstraZeneca
Study Director: Charles Bradley, PhD FibroGen
FibroGen
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP