Peginesatide for Anemia in Chronic Hemodialysis Patients

Anemia Clinical Trial

Official title:

A Phase 2, Open-label, Multi-center, Sequential, Dose Finding Study of the Safety, Pharmacodynamics, and Pharmacokinetics of Peginesatide Administered Intravenously for the Maintenance Treatment of Anemia in Chronic Hemodialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00228449
• Other study ID #: AFX01-03
• Status: Completed
• Phase: Phase 2
• First received: September 27, 2005
• Last updated: December 19, 2012
• Start date: July 2005
• Est. completion date: May 2007

Study information

• Verified date: December 2012
• Source: Affymax
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, pharmacodynamics (PD), and pharmacokinetics (PK) of multiple intravenous doses of peginesatide in participants with chronic kidney disease (CKD) who are on hemodialysis.

Description:

This was a Phase 2, multicenter, open-label, sequential, dose-finding trial designed with up to 12 treatment cohorts of 15 participants per cohort. Each participant received an intravenous dose of peginesatide administered once every 4 weeks (Q4W) for a total of 6 doses. Dosage regimens varied by cohort. Participants were followed for a minimum of 42 days after the last administration of peginesatide.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: May 2007
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant is informed of the investigational nature of this study and has given written, witnessed informed consent in accordance with institutional, local, and national guidelines;

• Males or females = 18 years of age. Pre-menopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening; those who are sexually active must practice a highly effective method of birth control for at least 4 weeks prior to study start, and must be willing to continue contraception until at least 4 weeks after the last dose of study drug. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence (only acceptable if practiced as a life-style and not acceptable if one who is sexually active practices abstinence only for the duration of the study) or vasectomized partner;

• Clinically stable on hemodialysis for =6 months prior to study drug administration;

• Urea clearance/volume (Kt/V) = 1.2 within the 4 weeks prior to study drug administration;

• Epoetin alfa maintenance therapy of = 60 and = 375 U/kg/wk continuously prescribed for 8 weeks prior to study drug administration. In the last 3 weeks prior to study drug administration, variation in prescribed total weekly dose must be = 25% from the mean of the last three prescribed total weekly doses;

• Three mid- or end-of-week hemoglobin values of = 10.0 and = 12.5 g/dL in the 3 weeks prior to study drug administration with = 1.2 g/dL difference between the three values;

• One serum ferritin level = 100 micrograms per liter (µg/L) or one transferrin saturation = 20% or one reticulocyte hemoglobin content (CHr) = 29 picograms within 4 weeks prior to study drug administration;

• One serum folate level above the lower limit of normal during the 4 weeks prior to study drug administration;

• One vitamin B12 level above the lower limit of normal during the 4 weeks prior to study drug administration;

• Weight = 45 kilograms (kg) within the 4 weeks prior to study drug administration;

• One white blood cell count = 3.0 x 10^9/L within 4 weeks prior to study drug administration; and

• One platelet count = 100 x 10^9/L and = 500 x 10^9/L within 4 weeks prior to study drug administration.

Exclusion Criteria:

• Known intolerance to erythropoiesis stimulating agents;

• History of antibodies to erythropoiesis stimulating agents or history of pure red cell aplasia;

• Known intolerance to parenteral iron supplementation;

• Red blood cell transfusion within 12 weeks prior to study drug administration;

• Hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all types, etc.);

• Known hemolysis;

• Chronic, uncontrolled, or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.);

• C-reactive protein greater than 30 mg/L within the 4 weeks prior to study drug administration;

• Moderate or significant infection within 2 weeks prior to study drug administration;

• Known coagulation disorder based on clinical context and laboratory [activated partial thromboplastin time (aPTT) or international normalized ratio (INR)] results;

• Temporary (untunneled) dialysis access catheter;

• Uncontrolled or symptomatic secondary hyperparathyroidism;

• Poorly controlled hypertension within the 4 weeks prior to study drug administration, per the Investigator's clinical judgment (e.g., systolic = 170 mm Hg or diastolic = 100 mm Hg on repeat readings);

• Any history of multiple significant drug allergies;

• History of severe or unstable reactive airway disease within the previous 10 years;

• Epileptic seizure in the 6 months prior to screening;

• Chronic congestive heart failure (New York Heart Association Class IV);

• High likelihood of early withdrawal or interruption of the study (e.g., myocardial infarction, severe or unstable coronary artery disease, stroke, respiratory, autoimmune, neuropsychiatric, or neurological abnormalities, liver disease including active hepatitis B or C, active HIV disease, or any other clinically significant medical disease or conditions in the prior 6 months that may, in the Investigator's opinion, interfere with assessment or follow-up of the patient);

• Evidence of malignancy within the past 5 years (except non-melanoma skin cancer which is not an exclusion criterion);

• Life expectancy < 12 months;

• Anticipated elective surgery during the study period; and

• Previous exposure to any investigational agent within 6 weeks prior to administration of study drug or planned receipt during the study period.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Chronic Kidney Disease
• Chronic Renal Failure
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• peginesatide

Locations

Country	Name	City	State
United States	Research Facility	Birmingham	Alabama
United States	Research Facility	Canton	Ohio
United States	Research Facility	Detroit	Michigan
United States	Research Facility	Lauderdale Lakes	Florida
United States	Research Facility	Los Angeles	California
United States	Research Facility	Minneapolis	Minnesota
United States	Research Facility	Mountain View	California
United States	Research Facility	Nashville	Tennessee
United States	Research Facility	New York	New York
United States	Research Facility	Norfolk	Virginia
United States	Research Facility	Pembroke Pines	Florida
United States	Research Facility	Pine Bluff	Arkansas
United States	Research Facility	San Antonio	Texas
United States	Research Facility	Shreveport	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Affymax

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average weekly hemoglobin and hemoglobin change from baseline		Baseline to Week 27	No
Secondary	Percentage of participants with hemoglobin within 1.0 gram per deciliter (g/dL) above or below baseline		Baseline to Week 25	No
Secondary	Percentage of participants who maintain hemoglobin within 9.5-13.0 g/dL		Baseline to Week 25	No
Secondary	Percentage of participants who maintain hemoglobin within 11.0-13.0 g/dL		Baseline to Week 25	No