A Phase 2 study of AF37702 Injection for anemia in patients with pure red cell aplasia.

Phase 1

Conditions: Anemia caused by Antibody-Mediated Pure Red Cell Aplasia in Patients with Chronic Kidney Disease
MedDRA version: 18.0Level: PTClassification code 10002965Term: Aplasia pure red cellSystem Organ Class: 10005329 - Blood and lymphatic system disorders
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2005-004944-30-DE

Lead Sponsor: Takeda Development Centre Europe Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 40

Inclusion Criteria

Patients who have confirmed antibody-mediated PRCA are potentially eligible for enrollment into this study. The following criteria must be documented in the patient's medical record at the time of diagnosis of PRCA:
i. Treatment with an ESA (e.g., epoetin or darbepoetin) with either a hemoglobin decrease while receiving a stable or increased dose of an ESA or requirement for blood transfusions
ii. Reticulocytes < 30,000 / mm3
iii. Bone marrow examination showing changes consistent with PRCA (i.e. markedly
decreased erythroid precursors in an otherwise normal marrow) or bone marrow
showing a normal number of erythroblasts without any excess blasts (e.g., less than
5%) and or any dysplastic features of the myeloid, erythroid or megakaryocytic
lineages.
iv. Demonstration of anti-EPO antibodies
- Patients must be = 18 years old at the time of consent.
- ESAs must be discontinued for a minimum of 1 months prior to screening and enrollment into the study.
- Periodic transfusions are required to maintain the hemoglobin.
- Hemoglobin < 10 g/dL for at least 2 measurements, obtained at least 1 week apart or the patient has received a transfusion within the past 4 week to achieve a hemoglobin > 10 g/dL (without ESA therapy).
- Anti-EPO antibody confirmed by the central reference laboratory for this study (Professor Casadevall, Service d'Hematologie Biologique, Hopital Hotel-Dieu, Paris, France) within 1 month prior to baseline.
- Patients can either be chronic kidney disease (CKD) patients not yet requiring renal replacement therapy (patients not on dialysis), those on regular hemodialysis or peritoneal dialysis, or following a renal transplant.
- Patients may or may not have previously been treated with immunosuppressive therapy. Except for patients with a renal transplant, immunosuppressive therapy should be stopped at least 4 weeks before commencement of the study; patients with a renal transplant will be allowed to remain on a stable maintenance immunosuppressive regimen.
- 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 a highly effective method of birth control throughout the study until at least 4 weeks prior to study start and must be willing to continue practicing birth control for at least 4 weeks after the last dose of study drug. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence (only acceptable if practiced as a life-style and not acceptable if one who is sexually active practices abstinence only for the duration of the study) or vasectomized partner.
- Written informed consent must be obtained.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

- Patients already successfully re-challenged with another erythropoietic agent.
- Abnormal bone marrow findings consistent with the diagnosis of myelodysplasia, a myeloproliferative disorder, hematologic malignancy (e.g., acute or chronic leukemia) or evidence of metastatic infiltration.
- Poorly controlled hypertension within 4 weeks prior to study drug administration, per investigator’s clinical judgment, e.g., systolic = 170 mm Hg, diastolic = 100 mm Hg on repeat readings.
- 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 (e.g., myocardial infarction, severe or unstable coronary artery disease, stroke, severe or unstable respiratory, liver or neuropsychiatric disease , or other clinically significant medical diseases or conditions within the prior 6 months that may, in the investigator’s opinion, interfere with safety, assessment or follow-up of the patient).
- Patients who refuse to give informed consent.
- Women who are pregnant, lactating or not using a medically approved birth control (e.g., barrier or hormonal contraception).
- Life expectancy < 12 months.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the ability of AF37702 Injection to increase and maintain increased hemoglobin levels in CKD patients (either not on dialysis, receiving regular hemodialysis or peritoneal dialysis, or following renal transplant) with confirmed antibody-mediated PRCA.;Secondary Objective: The secondary objectives are to evaluate in this patient population: (1) the safety of AF37702 Injection (including assessment of anti-erythropoietin and AF37702-specific antibody levels), (2) the effectiveness of AF37702 Injection in reducing the frequency of required red blood cell transfusions over time.;Primary end point(s): The proportion of patiens who increase and maintain hemoglobin levels (two consecutive values) greater than or equal to the lower limit of the target range in the absence of RBC transfusion in the previous 28 days by week 24.;Timepoint(s) of evaluation of this end point: Assessment according to protocol

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - The number of RBC transfusions and proportion of patients with RBC transfusions during the 26-week pre-treatment period (prior to enrollment) and during 13- and 26-week intervals during the study.<br>- Time to initial achievement of Hgb greater than or equal to the lower limit of the target range in the absence of RBC transfusions in the previous 28 days.;Timepoint(s) of evaluation of this end point: Assessment according to protocol

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