Clinical trial NCT00228449: Peginesatide for Anemia in Chronic Hemodialysis Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Chronic Kidney Disease
Chronic Renal Failure
Keywords: anemia
chronic kidney disease
CKD
chronic renal failure
CRF
dialysis
erythropoietin
EPO
erythropoiesis stimulating agent
ESA
Hematide™
hemodialysis
hemoglobin
Hb
Hgb
Omontys
peginesatide
red blood cell
red blood cell production
Lead sponsor: Affymax
Sponsor class: INDUSTRY
First posted: 2005-09-29
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Average weekly hemoglobin and hemoglobin change from baseline
timeFrame: Baseline to Week 27
Secondary outcomes:
measure: Percentage of participants with hemoglobin within 1.0 gram per deciliter (g/dL) above or below baseline
timeFrame: Baseline to Week 25
measure: Percentage of participants who maintain hemoglobin within 9.5-13.0 g/dL
timeFrame: Baseline to Week 25
measure: Percentage of participants who maintain hemoglobin within 11.0-13.0 g/dL
timeFrame: Baseline to Week 25
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Facility
state: Alabama
city: Pine Bluff
country: United States
facility: Research Facility
state: Arkansas
city: Los Angeles
country: United States
facility: Research Facility
state: California
city: Mountain View
country: United States
facility: Research Facility
state: California
city: Lauderdale Lakes
country: United States
facility: Research Facility
state: Florida
city: Pembroke Pines
country: United States
facility: Research Facility
state: Florida
city: Shreveport
country: United States
facility: Research Facility
state: Louisiana
city: Detroit
country: United States
facility: Research Facility
state: Michigan
city: Minneapolis
country: United States
facility: Research Facility
state: Minnesota
city: New York
country: United States
facility: Research Facility
state: New York
city: Canton
country: United States
facility: Research Facility
state: Ohio
city: Nashville
country: United States
facility: Research Facility
state: Tennessee
city: San Antonio
country: United States
facility: Research Facility
state: Texas
city: Norfolk
country: United States
facility: Research Facility
state: Virginia
Study officials:
affiliation: Affymax, Inc.
name: Affymax
role: STUDY_DIRECTOR
References:
citation: Besarab A, Zeig SN, Martin ER, Pergola PE, Whittier FC, Zabaneh RI, Schiller B, Mayo M, Francisco CA, Polu KR, Duliege AM. An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients. BMC Nephrol. 2012 Aug 30;13:95. doi: 10.1186/1471-2369-13-95.