Efficacy and Safety of Peginesatide (AF37702) in the Treatment of Anemia in Participants With Chronic Kidney Disease

An Open-Label Study to Investigate the Efficacy and Safety of AF37702 Injection in the Treatment of Anemia Caused by Antibody-Mediated Pure Red Cell Aplasia in Patients With Chronic Kidney Disease

The purpose of this study is to evaluate the ability of peginesatide (AF37702) to increase and maintain increased hemoglobin levels in participants with chronic kidney disease (CKD) (either not on dialysis, receiving regular hemodialysis or peritoneal dialysis, or following renal transplant) with confirmed antibody-mediated pure red cell aplasia (PRCA).

Study Overview

• Status: Completed
• Conditions: Anemia; Chronic Kidney Disease; Pure Red Cell Aplasia; Chronic Renal Failure
• Intervention / Treatment: Drug: Peginesatide

Detailed Description

The drug being tested in this study was peginesatide. Peginesatide injection was tested to investigate the efficacy and safety in the treatment of anemia caused by antibody-mediated pure red cell aplasia in participants with chronic kidney disease.

The study enrolled 22 patients. All the participants enrolled into the study received:

• Peginesatide 0.5 mg/kg subcutaneous (SC) injection

The participants received a starting dose of 0.05 mg/kg (every 4 weeks) followed by 0.1 mg/kg dose, based on the assessment of the dose response in the initial group of 5 participants. The frequency of each injection and the dose adjusted based on the participant's hemoglobin response and the ability to maintain a hemoglobin level in the range of 10.0-12.0 g/dL.

This multi-center trial was conducted in Europe. The overall time to participate in this study was 10 years and 7 months approximately. Participants made multiple visits to the clinic until the projected end of treatment period, which was 31-Oct-2016.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Research Facility
• Germany
  • Erlangen, Germany
    • Research Facility
• United Kingdom
  • Derby, United Kingdom
    • Research Facility
  • London, United Kingdom
    • Research Facility

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants who have confirmed antibody-mediated Pure red cell aplasia (PRCA) are potentially eligible for enrollment into this study.
• Participants must be ≥ 18 years old at the time of consent.
• Erythropoiesis stimulating agents (ESAs) must be discontinued for a minimum of 1 month prior to screening.
• Participant requires periodic transfusions to maintain hemoglobin.
• Hemoglobin < 10 g/dL for at least 2 measurements or participant has received a transfusion within the past 4 weeks to achieve a hemoglobin > 10 g/dL.
• Confirmation that an anti-erythropoietin antibody sample was obtained for analysis by the central reference laboratory within 1 month prior to baseline.
• Participants can either be participants with chronic kidney disease not yet requiring renal replacement therapy (participants not on dialysis), those on regular hemodialysis or peritoneal dialysis, or following a renal transplant.
• Participants may or may not have previously been treated with immunosuppressive therapy.
• Pre-menopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening.
• Written informed consent must be obtained.

Exclusion Criteria:

• Participants already successfully on another erythropoietic agent.
• Abnormal bone marrow findings consistent with the diagnosis of myelodysplasia, a myeloproliferative disorder, hematologic malignancy or evidence of metastatic infiltration.
• Poorly controlled hypertension.
• Previous exposure to any investigational agent within 4 weeks prior to administration of study drug or planned receipt during the study period.
• High likelihood of early withdrawal or interruption of the study.
• Participants who refuse to give informed consent.
• Women who are pregnant, lactating or not using a medically approved birth control.
• Life expectancy <12 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Peginesatide; Peginesatide 0.05 mg/kg injection, subcutaneously as a starting dose followed by peginesatide 0.1 mg/kg injection, subcutaneously once every 4 weeks for up to 6 months. Individual dose of peginesatide injection was modified based on hemoglobin levels. Dose adjustments were made in order to achieve and maintain hemoglobin in the target range of 10.0-12.0 g/dL.	Drug: Peginesatide; Peginesatide injection; Other Names: Omontys; Hematide; AF37702

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Increase and Maintain Hemoglobin Levels (Two Consecutive Values) Greater Than or Equal to the Lower Limit of the Target Range in the Absence of Red Blood Cell Transfusion in the Previous 28 Days by Week 24	Percentage of participants who experienced increase and maintain hemoglobin levels (two consecutive values) greater than or equal to the lower limit (11 g/dL) in the absence of red blood cell transfusion in the previous 28 days by week 24 were reported.	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Red Blood Cells (RBCs) Transfusions During the 26 Weeks Pre-treatment Period (Prior to Enrollment) and During 13- and 26 Weeks Intervals During the Study		26 weeks prior to enrollment up to end of study (up to 60 months)
Percentage of Participants With RBC Transfusions During the 26-week Pre-treatment Period and During 13- and 26-week Intervals During the Study		26 weeks prior to enrollment up to end of study (up to 60 months)
Time to Initial Achievement of Hemoglobin (Hgb) Greater Than or Equal to the Lower Limit of the Target Range in the Absence of Red Blood Cell Transfusions in the Previous 28 Days	The time between first dose administered and the initial achievement of a Hgb increase ≥11 g/dL for two consecutive visits was calculated for each participant as the number of days between the first dose administration date and the earlier of (1) the study termination date [i.e. censor date] and (2) the first date of an Hgb increase ≥ 11 g/dL for two consecutive visits without whole blood or RBC transfusion during the previous 28 days. Time to initial Hgb increase ≥ 11 g/dL will be calculated for each participant as the minimum of censor date and increase date minus the first dose date plus 1.	Up to 60 months
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.	From signing of informed consent form up to Month 60

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Macdougall IC, Rossert J, Casadevall N, Stead RB, Duliege AM, Froissart M, Eckardt KU. A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia. N Engl J Med. 2009 Nov 5;361(19):1848-55. doi: 10.1056/NEJMoa074037.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2006
• Primary Completion (Actual): October 24, 2016
• Study Completion (Actual): October 31, 2016

Study Registration Dates

• First Submitted: April 13, 2006
• First Submitted That Met QC Criteria: April 13, 2006
• First Posted (Estimate): April 17, 2006

Study Record Updates

• Last Update Posted (Actual): March 14, 2019
• Last Update Submitted That Met QC Criteria: November 27, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Drug Therapy; hemoglobin; anemia; chronic kidney disease; erythropoiesis stimulating agent; CKD; CRF; Hgb; erythropoietin; PRCA; chronic renal failure; EPO; ESA; Hb; red blood cell; red blood cell production; pure red cell aplasia
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Anemia; Red-Cell Aplasia, Pure
• Other Study ID Numbers: AFX01-06; 2005-004944-30 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No