Safety, PD & PK of Multiple Doses of Peginesatide for Anemia in Chronic Kidney Disease Patients

Sponsor

Affymax (Industry)

Overall Status

Completed

CT.gov ID

NCT00228436

Collaborator

(none)

139

Enrollment

Locations

Arms

Duration (Months)

10.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the safety, pharmacodynamics (PD), and pharmacokinetics (PK) of multiple subcutaneous injections of peginesatide in participants with chronic kidney disease (CKD) not on dialysis who had not received erythropoiesis stimulating agent (ESA) treatment.

Condition or Disease	Intervention/Treatment	Phase
Anemia Chronic Kidney Disease Chronic Renal Failure	Drug: peginesatide	Phase 2

Detailed Description

This was a Phase 2, dose finding study designed to evaluate peginesatide treatment of participants with CKD not on ESA treatment. The objective was to determine the range of doses of peginesatide administered subcutaneously once every 4 weeks (Q4W) that increased and maintained hemoglobin at 11 to 13 g/dL.

Study Design

Study Type:

Interventional

Actual Enrollment :

139 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Open-label, Multi-center, Sequential Dose Finding Study of the Safety, Pharmacodynamics, and Pharmacokinetics of Multiple Doses of Subcutaneously Administered Peginesatide in Chronic Kidney Disease Patients Not on Dialysis and Not on Erythropoiesis Stimulating Agent (ESA) Treatment

Study Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Peginesatide starting dose of 0.05 milligram per kilogram (mg/kg) administered subcutaneously (SC) once every 4 weeks (Q4W) for a total of 6 doses.	Drug: peginesatide Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 2 Peginesatide starting dose of 0.075 mg/kg administered SC Q4W for a total of 6 doses.	Drug: peginesatide Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 3 Peginesatide starting dose of 0.025 mg/kg administered SC Q4W for a total of 6 doses.	Drug: peginesatide Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 4 Peginesatide starting dose of 0.05 mg/kg administered intravenously (IV) Q4W for a total of 6 doses.	Drug: peginesatide Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 5 Peginesatide starting dose of 0.025 mg/kg administered SC once every 2 weeks (Q2W) for a total of 12 doses.	Drug: peginesatide Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 6 Peginesatide starting dose of 0.0375 mg/kg administered SC Q2W for a total of 12 doses.	Drug: peginesatide Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 7 Peginesatide fixed starting dose of 4 mg administered SC Q4W for a total of 6 doses.	Drug: peginesatide Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 8 Peginesatide fixed starting dose of 3 mg administered SC Q4W for a total of 6 doses.	Drug: peginesatide Other Names: Omontys Hematide AF37702 Injection

Outcome Measures

Primary Outcome Measures

Percentage of participants who achieved a target hemoglobin response during the study. [25 weeks]
A target hemoglobin response is defined as a hemoglobin increase of ≥ 1.0 gram per deciliter (g/dL) from baseline and a hemoglobin value ≥ 11.0 g/dL during the study.

Secondary Outcome Measures

Incidence of adverse events and serious adverse events [25 weeks]
Pharmacokinetic parameters [25 weeks]
Percentage of participants with hemoglobin values in the range of 11.0 to 13.0 g/dL throughout the study. [25 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 and ≤ 85 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 an adequate form of contraception for at least 4 weeks prior to study start, and must be willing to continue contraception for at least 4 weeks after the last dose of study drug;
Chronic kidney disease stage 3 or 4 (estimated Glomerular filtration rate [GFR] of 15-60 mL/min within 28 days prior to study drug administration) and not expected to begin dialysis for at least 12 weeks;
Two hemoglobin values of ≥ 9.0 and < 11.0 g/dL within 14 days prior to study drug administration, including at least one of the values drawn within 7 days prior to study drug administration;
One serum ferritin level ≥ 100 micrograms per liter (μg/L) and transferrin saturation ≥ 20 % within 4 weeks prior to study drug administration;
One serum or red cell folate level above lower limit of normal within 4 weeks prior to study drug administration;
One vitamin B12 level above lower limit of normal within 4 weeks prior to study drug administration;
Weight ≥ 45 kg within 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 within 4 weeks prior to study drug administration.

Exclusion Criteria:

Prior treatment with any erythropoiesis stimulating agent in the 12 weeks prior to study drug administration;
Any prior treatment with Eprex®;
Known intolerance to any erythropoiesis stimulating agent;
History of antibodies to any erythropoiesis stimulating agent or history of pure red cell aplasia;
Prior hemodialysis or peritoneal dialysis treatment;
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 (sickle-cell trait does not exclude patient), thalassemia of all types, etc.];
Known hemolysis;
Chronic, uncontrolled, or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.);
C Reactive Protein (CRP) greater than 30 mg/L within the 4 weeks prior to study drug administration;
Febrile illness within 7 days prior to study drug administration;
Uncontrolled or symptomatic secondary hyperparathyroidism;
Poorly controlled hypertension within 4 weeks prior to study drug administration, per Investigator's clinical judgment (e.g. systolic ≥ 170mm Hg, diastolic ≥ 100 mm Hg on repeat readings);
Epileptic seizure in the 6 months prior to study drug administration;
Chronic congestive heart failure (New York Heart Association Class IV);
High likelihood of early withdrawal or interruption of the study;
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.

Contacts and Locations

Locations

	Site	City	Country
1	Research Facility	Białystok	Poland
2	Research Facility	Gdansk	Poland
3	Research Facility	Katowice	Poland
4	Research Facilities	Kraków	Poland
5	Research Facility	Warszawa	Poland
6	Research Facility	Łódź	Poland
7	Research Facility	Coventry	United Kingdom
8	Research Facility	Croydon	United Kingdom
9	Research Facility	Derby	United Kingdom
10	Research Facility	Leicester	United Kingdom
11	Research Facilities	London	United Kingdom
12	Research Facility	Salford	United Kingdom
13	Research Facility	Swansea	United Kingdom