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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Anemia, Chronic Kidney Disease, Chronic Renal Failure, Pure Red Cell Aplasia

Intervention / Treatment
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* Drug: Peginesatide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peginesatide<br>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<br>* Peginesatide injection<br>* Other names: AF37702;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy, pure red cell aplasia, PRCA, chronic kidney disease, CKD, chronic renal failure, CRF, anemia, erythropoietin, EPO, erythropoiesis stimulating agent, ESA, hemoglobin, Hb, Hgb, red blood cell, red blood cell production