Strategies Using Darbepoetin Alfa to Avoid Transfusions in Chronic Kidney Disease | NCT01652872 | Trialant

Strategies Using Darbepoetin Alfa to Avoid Transfusions in Chronic Kidney Disease | NCT01652872 | Trialant

Official Title: Strategies Using Darbepoetin Alfa to Avoid Transfusions in Chronic Kidney Disease
Brief Summary: A phase 3, multicenter, randomized, double-blind, parallel group study. Anemic subjects with chronic kidney disease (CKD) and not on dialysis will be randomized 1:1 to 1 of 2 dosing strategies to evaluate the proportion of subjects receiving at least one red blood cell (RBC) transfusion. In the haemoglobin (Hb)-based titration group, darbepoetin alfa doses will be titrated to maintain Hb ≥ 10.0 grams/deciliter (g/dL). In the fixed dose group, subjects will receive a fixed dose of darbepoetin alfa. Treatment group, darbepoetin alfa doses, and protocol specified Hb concentrations will be blinded. Subjects will be followed for approximately 2 years from the date of randomization.
Detailed Description: The study is a phase 3, multicenter, randomized, double-blind, parallel group study designed to describe the benefits and potential risks of a new treatment strategy using a fixed dose of darbepoetin alfa in subjects with CKD and not on dialysis. Anemic subjects without recent use of an erythropoiesis stimulating agent (ESA) will be randomly allocated 1:1 to treatment with a fixed dose of darbepoetin alfa or to treatment with darbepoetin alfa using a Hb-based titration strategy, which has been the conventional dosing strategy. In the Hb-based titration group, darbepoetin alfa doses will be titrated to maintain Hb ≥ 10.0 g/dL. This study aims to estimate the incidence of RBC transfusions (administered as deemed clinically necessary) in each group and the difference in incidence of RBC transfusions between the 2 groups. In addition, multiple aspects, such as cumulative darbepoetin alfa dose, total number of units of transfusions, Hb concentration, Hb-related parameters (eg, Hb variability, excursions, rate of change), and adverse (eg, cardiovascular) events, will also be considered in order to determine a preferred dosing regimen. Treatment group, darbepoetin alfa doses, and protocol specified Hb concentrations will be blinded to the investigator, subjects and study team. Subjects will be followed for approximately 2 years from the date of randomization.

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Eligibility Criteria: Key Inclusion Criteria:

Clinical history of advanced CKD not on dialysis with at least 1 historic estimated glomerular filtration rate (eGFR) < 45.0 mL/mi)/1.73 m2 at least 12 weeks prior to screening

Not currently receiving dialysis with an eGFR < 45.0 mL/min/1.73m2, per the central laboratory during screening

Chronic anemia due to renal failure

Two Hb concentrations < 10.0 g/dL, at least 2 weeks apart during screening using the modified Hb point of care (POC) device

Iron replete, defined as a transferrin saturation (TSAT) ≥ 20% and a ferritin ≥ 100 ng/mL, per the central laboratory during screening

Vitamin B12 and folate replete, defined as a vitamin B12 level > 180 pg/mL and a folate concentration > 7 nmol/L, per the central laboratory during screening

Clinically stable in the opinion of the investigator

Subject has provided written informed consent

Key Exclusion Criteria:

Systemic hematologic disease (eg, sickle cell anemia, myelodysplastic syndrome, hematologic malignancy)

Current or prior malignancy within 5 years of screening, with the exception of non-melanoma skin cancers and cervical intraepithelial neoplasia

Treatment for any malignancy (eg, radiation, chemotherapy, hormone therapy, or biologics) within 5 years of screening, with the exception of locally excised non-melanoma skin cancer or cervical intraepithelial neoplasia

Female subject not willing to use highly effective methods of birth control during treatment and for 4 weeks after the end of treatment

Subject is pregnant or breast feeding, or might become pregnant during the study or within 4 weeks after the end of treatment

Currently receiving intravenous (IV) antibiotics for treatment of an active infection

Known Human Immunodeficiency Virus (HIV) positive

Currently receiving systemic immunosuppressive therapy with the exception of prednis(ol)one ≤ 10 mg per day (or the steroid equivalent)

History of any organ transplant

Currently enrolled in another interventional study (eg, studies which require medical device use or drug therapy or with protocol required procedures), or less than 4 weeks since ending another interventional study(s) or receiving investigational agent(s)

Known neutralizing anti-erythropoietic protein antibodies

Known sensitivity to any of the products to be administered during dosing

Previously enrolled in this study

Not expected to be available for protocol required study visits or procedures to the best of the subject and investigator's knowledge

Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with all required study procedures

Occurrence of stroke or myocardial infarction (MI) within 24 weeks of screening

Receipt of RBC transfusion within 8 weeks of screening

Occurrence of seizure, clinically relevant active bleeding (eg, gastrointestinal [GI] bleed) or any hospitalization within 8 weeks of screening

Receipt of any IV iron therapy within 4 weeks of screening

Changes in oral iron therapy within 4 weeks of screening

Receipt of ESA therapy within 4 weeks of screening

Diagnosis or treatment of malignancy, with the exception of non-melanoma skin cancers and cervical intraepithelial neoplasia during screening

Receipt of ESA therapy, RBC transfusions, IV iron therapy during screening

Changes in oral iron therapy during screening

Occurrence of stroke, MI, seizure, clinically relevant active bleeding (eg, GI bleed), any hospitalization or outpatient surgery during screening

Uncontrolled hypertension during screening. Defined in this study, as a mean systolic blood pressure > 140 mmHg at both screening visits, or a mean systolic blood pressure >/= 160 mmHg at any screening visit, or a mean diastolic blood pressure >/= 90 mmHg at any screening visit.

Expected or scheduled change in oral iron therapy or receipt of IV iron therapy within 4 weeks after randomization

Expected or scheduled receipt of a RBC transfusion within 8 weeks after randomization

Expected or scheduled organ transplant within 24 weeks after randomization

Expected or scheduled initiation of dialysis within 24 weeks after randomization