Clinical trial NCT00314795: Efficacy and Safety of Peginesatide (AF37702) in the Treatment of Anemia in Participants With Chronic Kidney Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Chronic Kidney Disease
Chronic Renal Failure
Pure Red Cell Aplasia
Keywords: 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
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2006-04-17
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Up to Week 24
Secondary outcomes:
measure: 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
timeFrame: 26 weeks prior to enrollment up to end of study (up to 60 months)
measure: Percentage of Participants With RBC Transfusions During the 26-week Pre-treatment Period and During 13- and 26-week Intervals During the Study
timeFrame: 26 weeks prior to enrollment up to end of study (up to 60 months)
measure: 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
timeFrame: Up to 60 months
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation
timeFrame: From signing of informed consent form up to Month 60
Other outcomes:
Locations:
city: Paris
country: France
facility: Research Facility
city: Erlangen
country: Germany
facility: Research Facility
city: Derby
country: United Kingdom
facility: Research Facility
city: London
country: United Kingdom
facility: Research Facility
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.