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

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

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.

Study Overview

• Status: Completed
• Conditions: Anemia; Chronic Kidney Disease; Chronic Renal Failure
• Intervention / Treatment: Drug: peginesatide

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 Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Białystok, Poland
    • Research Facility
  • Gdansk, Poland
    • Research Facility
  • Katowice, Poland
    • Research Facility
  • Kraków, Poland
    • Research Facilities
  • Warszawa, Poland
    • Research Facility
  • Łódź, Poland
    • Research Facility
• United Kingdom
  • Coventry, United Kingdom
    • Research Facility
  • Croydon, United Kingdom
    • Research Facility
  • Derby, United Kingdom
    • Research Facility
  • Leicester, United Kingdom
    • Research Facility
  • London, United Kingdom
    • Research Facilities
  • Salford, United Kingdom
    • Research Facility
  • Swansea, United Kingdom
    • Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants who achieved a target hemoglobin response during the study.	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.	25 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Affymax

Publications and helpful links

General Publications

• Macdougall IC, Wiecek A, Tucker B, Yaqoob M, Mikhail A, Nowicki M, MacPhee I, Mysliwiec M, Smolenski O, Sulowicz W, Mayo M, Francisco C, Polu KR, Schatz PJ, Duliege AM. Dose-finding study of peginesatide for anemia correction in chronic kidney disease patients. Clin J Am Soc Nephrol. 2011 Nov;6(11):2579-86. doi: 10.2215/CJN.10831210. Epub 2011 Sep 22.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: September 27, 2005
• First Submitted That Met QC Criteria: September 27, 2005
• First Posted (Estimate): September 29, 2005

Study Record Updates

• Last Update Posted (Estimate): December 21, 2012
• Last Update Submitted That Met QC Criteria: December 19, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: hemoglobin; anemia; chronic kidney disease; erythropoiesis stimulating agent; dialysis; CKD; CRF; Hgb; erythropoietin; chronic renal failure; EPO; ESA; Hematide™; Hb; Omontys; peginesatide; red blood cell; red blood cell production
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Anemia
• Other Study ID Numbers: AFX01-04; 2005-002218-39 (EudraCT Number)