Safety and Efficacy Study of Hematide Injection in Chronic Renal Failure Subjects. - Full Text View

Sponsors and Collaborators:	Takeda Global Research & Development Center, Inc. Affymax
Information provided by:	Takeda Global Research & Development Center, Inc.
ClinicalTrials.gov Identifier:	NCT00752609

Purpose

The purpose of this study is to determine the efficacy and safety of Hematide in patients with chronic renal failure who are previously treated with Darbepoetin Alfa .

Condition	Intervention	Phase
Anemia	Drug: Hematide	Phase II

MedlinePlus related topics: Anemia Dialysis Kidney Failure

Drug Information available for: Darbepoetin alfa

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase 2 Study of the Safety and Efficacy of Hematide Injection for the Maintenance Treatment of Anemia in Subjects With Chronic Renal Failure Who Are on Hemodialysis or Do Not Require Dialysis and Previously Treated With Darbepoetin Alfa

Further study details as provided by Takeda Global Research & Development Center, Inc.:

Primary Outcome Measures:

Mean change in hemoglobin between baseline and the evaluation period. [ Time Frame: Weeks 19, 20, 21, 22, 23 and 24. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of subjects who have mean hemoglobin values within the target range of 10.0-12.0 g/dL. [ Time Frame: Weeks 19, 20, 21, 22, 23 and 24. ] [ Designated as safety issue: No ]
Proportion of subjects with a change in hemoglobin between baseline and the evaluation period of ≤ ± 1 g/dL. [ Time Frame: Weeks 19, 20, 21, 22, 23 and 24. ] [ Designated as safety issue: No ]
Proportion of subjects who receive red blood cell transfusions. [ Time Frame: Weeks 0 through 24 ] [ Designated as safety issue: No ]
Mean hemoglobin during 4-week intervals. [ Time Frame: Weeks 0 through 3, 4 through 7, 8 through 11, 12 through 15, 16 through 19, and 20 through 24. ] [ Designated as safety issue: No ]
Proportion of subjects who maintain a target hemoglobin of 10.0-12.0 g/dL during 4-week intervals. [ Time Frame: Weeks 0 through 3, 4 through 7, 8 through 11, 12 through 15, 16 through 19, and 20 through 24. ] [ Designated as safety issue: No ]
Proportion of subjects requiring dose adjustments during the study [ Time Frame: Weeks 0 through 24 ] [ Designated as safety issue: No ]
Adverse events and serious adverse events. [ Time Frame: Weeks 0 through 24 ] [ Designated as safety issue: Yes ]
Composite safety endpoint (death [all causes], stroke, myocardial infarction, congestive heart failure, unstable angina and arrhythmia). [ Time Frame: Weeks 0 through 24 ] [ Designated as safety issue: Yes ]
Physical examination (weight). [ Time Frame: Weeks: 0, 12 and 24. ] [ Designated as safety issue: Yes ]
Physical examination (vital signs and oral temperature). [ Time Frame: Weeks: 0, 4, 8, 12, 14, 20 and 24. ] [ Designated as safety issue: Yes ]
Clinical laboratory tests (chemistry and hematology). [ Time Frame: Weeks: 0, 4, 8, 12, 14, 20 and 24. ] [ Designated as safety issue: Yes ]
Clinical laboratory tests (hemoglobin) [ Time Frame: Weeks 0 through 24. ] [ Designated as safety issue: Yes ]
Proportion of subjects with confirmed (2 consecutive values) hemoglobin outside the range of 10.0-12.0 g/dL. [ Time Frame: Weeks 0 through 24. ] [ Designated as safety issue: Yes ]
Proportion of subjects with confirmed (2 consecutive values) hemoglobin values ≥12.0 g/dL, ≥13.0 g/dL, and ≥14.0 g/dL. [ Time Frame: Weeks 0 through 24. ] [ Designated as safety issue: Yes ]
Proportion of subjects with hemoglobin increases of >1.0 g/dL in any 2-week interval during the Titration and Evaluation periods. [ Time Frame: Weeks 0 through 3, 4 through 7, 8 through 11, 12 through 15, 16 through 19, and 20 through 24. ] [ Designated as safety issue: Yes ]
Proportion of subjects with hemoglobin increases of >2.0 g/dL in any 4-week interval during the Titration and Evaluation periods. [ Time Frame: Weeks 0 through 3, 4 through 7, 8 through 11, 12 through 15, 16 through 19, and 20 through 24. ] [ Designated as safety issue: Yes ]
Incidence of Hematide-specific antibody formation. [ Time Frame: Weeks: 0, 4, 8, 12, 14, 20 and 24. ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	100
Study Start Date:	October 2008
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1.: Experimental	Drug: Hematide 0.04 to 0.16 mg/kg Hematide injection, subcutaneously or intravenously, once every 4 weeks for 24 weeks.

Detailed Description:

Anemia, resulting primarily from insufficient production of erythropoietin to support erythropoiesis, is a common consequence of chronic renal failure. Both North America and Europe have established clinical practice guidelines for the treatment and hemoglobin targets in chronic renal failure patients. These guidelines recommend the use of ESAs. The benefits of ESA therapy include reduced fatigue, improved QoL, decreased cardiovascular mortality risk and improved cardiovascular function. An increase risk of death and serious cardiovascular and thromboembolic events, including myocardial infarction, stroke, congestive heart failure, and hemodialysis graft occlusion have been observed in controlled clinical trials of ESAs when administered to target Hgb levels of ≥13.5 g/dL. The vast majority of patients receiving hemodialysis receive ESA therapy to treat their anemia and most patients begin ESA therapy prior to any requirement for dialysis.

There are several common clinical situations in which anemia appears to be the result of hypoproliferation of red blood cell precursors associated with an absolute or relative deficiency of erythropoietin. These include the anemias associated with chronic kidney disease or chronic renal failure, inflammation (anemia of chronic disease, such as rheumatoid arthritis) and the anemia associated with cancer with or without myelosuppressive chemo and radiation therapies. In these situations, recombinant human erythropoietin has been used successfully to increase hemoglobin levels, reduce fatigue, improve daily function, and alleviate a wide range of symptoms, including decreased cognition, palpitations, dyspnea, dizziness and depression.

Anemia of chronic renal failure is due to several factors, primarily the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin. Ancillary factors also include the shortened lifespan of red blood cells, iron and other nutritional deficiencies, infection, and inflammation. The prevalence of anemia increases with progressive deterioration of renal function, and affects more than 90% of patients with chronic renal failure Stage 5 (End Stage Renal Disease). Anemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function and exercise capacity, increased left ventricular hypertrophy and heart failure. Treatment of anemia reduces morbidity and mortality risks and may improve quality of life. Therefore, anemia should be diagnosed and treated early.

Erythropoiesis stimulating agents have been established as a treatment for anemia in chronic renal failure subjects, and have improved the management of anemia over alternatives such as transfusion. Hematide is a parenteral formulation being developed for the correction of anemia in patients with chronic renal failure, and binds to and activates the human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in a manner similar to other known erythropoiesis-stimulating agents.

Subjects participating in this study will receive variable doses of Hematide injection once every four weeks. Total commitment time for this study is about 30 weeks.

Eligibility

Ages Eligible for Study:	18 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

A female subject of childbearing potential who are sexually active agree to routinely use acceptable contraception from Screening throughout the duration of the study.
The subject has chronic renal failure and meets one of the following criteria:
- Has been on hemodialysis for ≥6 months prior to enrollment, or
- Has not yet begun dialysis (hemodialysis or peritoneal dialysis) and is not anticipated to transition to dialysis during participation in the study.
The subject is on stable darbepoetin alfa maintenance therapy (either subcutaneous or intravenous) continuously prescribed for a minimum of 8 weeks prior to enrollment.
The subject has 4 consecutive hemoglobin values with a mean ≥10.0 and ≤12.0 g/dL during the Screening Period, with the difference between the mean of the first 2 consecutive hemoglobin values and the mean of the last 2 consecutive values being ≤1.0 g/dL.
The subject has 1 ferritin level ≥100 ng/mL within 4 weeks prior to enrollment.
The subject has 1 serum or red cell folate level ≥ lower limit of normal within 4 weeks prior to enrollment.
The subject has 1 vitamin B12 level ≥ lower limit of normal within 4 weeks prior to enrollment.
The subject has a negative test result for hepatitis B surface antigen, and hepatitis C virus antibody at Screening and no known history of human immunodeficiency virus infection.

Exclusion Criteria:

If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 28 days after the end of this study; or intending to donate ova during such time period.
The subject has known intolerance to any erythropoiesis-stimulating agent, parenteral iron supplementation, or PEGylated molecules.
The subject has known bleeding or coagulation disorder.
The subject has known hematologic disease or cause of anemia other than renal disease (eg, PRCA, homozygous sickle-cell disease, thalassemia, multiple myeloma, hemolytic anemia and myelodysplastic syndrome).
The subject has had red blood cell or whole blood transfusion within 12 weeks prior to enrollment.
The subject has received a recent course of intensive iron replacement (ie, has received more than 500mg intravenously in the 28 days prior to enrollment).
The subject has poorly controlled hypertension within 4 weeks prior to enrollment, per investigator's clinical judgment.
The subject has advanced chronic congestive heart failure - New York Heart Association Class III or IV.
The subject has uncontrolled, or symptomatic inflammatory disease (eg, rheumatoid arthritis, systemic lupus erythematosus, etc.)
The subject has a known history of seizure disorder or received anti-epileptic medication for seizure disorder within 6 months prior to enrollment.
The subject has any clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
The subject has evidence of active malignancy within past 5 years (except non-melanoma skin cancer or carcinoma-in-situ that has been completely excised).
The subject has a scheduled kidney transplant (Note: subjects currently on a transplant wait list are not excluded unless there is an identified donor).
The subject is anticipated to initiate dialysis during the course of the study (only applies to subjects who are not yet on dialysis).
The subject has a temporary dialysis access catheter (only applies to subjects receiving dialysis).
The subject has a scheduled surgery that may be expected to lead to significant blood loss.
The subject has previous exposure to any investigational agent within 4 weeks prior to enrollment, or planned receipt of an investigational agent, other than as specified by this protocol, during the study period.
The subject has previous exposure to Hematide Injection.
The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to enrollment.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00752609

Contacts

Contact: Takeda Study Registration Call Center

800-778-2860

medicalinformation@tpna.com

Locations

United States, California
	Recruiting
Los Angeles, California, United States
United States, Florida
	Recruiting
Lauderdale Lakes, Florida, United States
United States, Mississippi
	Recruiting
Columbus, Mississippi, United States
United States, New York
	Recruiting
Mineola, New York, United States

Sponsors and Collaborators

Takeda Global Research & Development Center, Inc.

Affymax

Investigators

Study Director:

Medical Director

Takeda Global Research & Development Center, Inc.

More Information

Responsible Party:	Takeda Global Research & Development Center, Inc. ( Sr. VP, Clinical Science )
Study ID Numbers:	AFX01_202, 2008-003459-64
Study First Received:	September 11, 2008
Last Updated:	December 8, 2008
ClinicalTrials.gov Identifier:	NCT00752609
Health Authority:	United States: Food and Drug Administration; European Union: European Medicines Agency; Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Takeda Global Research & Development Center, Inc.:

Anemia
Drug Therapy
Hemodialysis
Kidney Failure

Study placed in the following topic categories:

Renal Insufficiency
Urologic Diseases
Renal Insufficiency, Chronic
Hematologic Diseases
Darbepoetin alfa

Anemia
Kidney Failure, Chronic
Kidney Diseases
Kidney Failure

ClinicalTrials.gov processed this record on January 16, 2009