Strategies Using Darbepoetin Alfa to Avoid Transfusions in Chronic Kidney Disease

Anemia in Chronic Kidney Disease Patients Not on Dialysis Clinical Trial

— START-CKD  

Official title:

Strategies Using Darbepoetin Alfa to Avoid Transfusions in Chronic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01652872
• Other study ID #: 20110226
• Status: Completed
• Phase: Phase 3
• Start date: July 30, 2012
• Est. completion date: October 19, 2017

Study information

• Verified date: September 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 756
• Est. completion date: October 19, 2017
• Est. primary completion date: October 19, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia in Chronic Kidney Disease Patients Not on Dialysis
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Biological:
• Darbepoetin alfa
Darbepoetin alfa was presented as single use prefilled syringes (PFS). Investigational product was administered SC Q4W for the duration of the treatment period.

Other:
• Placebo
Placebo was presented as single use PFS. Participants received a SC placebo injection in place of darbepoetin alfa therapy when the dose of study drug was withheld per the dosing algorithm for the duration of the treatment period.

Locations

Country	Name	City	State
Puerto Rico	Research Site	Caguas
Puerto Rico	Research Site	Ponce
Puerto Rico	Research Site	Ponce
Puerto Rico	Research Site	Rio Piedras
Puerto Rico	Research Site	San Juan
Puerto Rico	Research Site	San Juan
United States	Research Site	Albany	New York
United States	Research Site	Alexandria	Virginia
United States	Research Site	Alhambra	California
United States	Research Site	Ames	Iowa
United States	Research Site	Anaheim	California
United States	Research Site	Anderson	South Carolina
United States	Research Site	Anniston	Alabama
United States	Research Site	Arlington	Texas
United States	Research Site	Arvada	Colorado
United States	Research Site	Asheville	North Carolina
United States	Research Site	Atlanta	Georgia
United States	Research Site	Augusta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Austin	Texas
United States	Research Site	Austin	Texas
United States	Research Site	Azusa	California
United States	Research Site	Bakersfield	California
United States	Research Site	Bakersfield	California
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Beaver	Pennsylvania
United States	Research Site	Bell Gardens	California
United States	Research Site	Bethesda	Maryland
United States	Research Site	Bethlehem	Pennsylvania
United States	Research Site	Beverly Hills	California
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bluefield	West Virginia
United States	Research Site	Boynton Beach	Florida
United States	Research Site	Bristol	Tennessee
United States	Research Site	Bronx	New York
United States	Research Site	Brooklyn	New York
United States	Research Site	Buffalo	New York
United States	Research Site	Burlington	Vermont
United States	Research Site	Canton	Georgia
United States	Research Site	Cerritos	California
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Chesapeake	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Chula Vista	California
United States	Research Site	Columbia	South Carolina
United States	Research Site	Columbia	Tennessee
United States	Research Site	Columbus	Indiana
United States	Research Site	Columbus	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Columbus	Mississippi
United States	Research Site	Coral Springs	Florida
United States	Research Site	Corsicana	Texas
United States	Research Site	Cudahy	California
United States	Research Site	Dallas	Texas
United States	Research Site	Daytona Beach	Florida
United States	Research Site	DeLand	Florida
United States	Research Site	Doylestown	Pennsylvania
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Durham	North Carolina
United States	Research Site	Dyersburg	Tennessee
United States	Research Site	Eatontown	New Jersey
United States	Research Site	Edinburg	Texas
United States	Research Site	El Centro	California
United States	Research Site	El Paso	Texas
United States	Research Site	Evanston	Illinois
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fargo	North Dakota
United States	Research Site	Fargo	North Dakota
United States	Research Site	Flint	Michigan
United States	Research Site	Flushing	New York
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fountain Valley	California
United States	Research Site	Framingham	Massachusetts
United States	Research Site	Franklin	Tennessee
United States	Research Site	Frisco	Texas
United States	Research Site	Fullerton	California
United States	Research Site	Garden Grove	California
United States	Research Site	Glendale	California
United States	Research Site	Goodyear	Arizona
United States	Research Site	Granada Hills	California
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United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Great Neck	New York
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greenville	North Carolina
United States	Research Site	Greenville	Texas
United States	Research Site	Greenville	South Carolina
United States	Research Site	Gulfport	Mississippi
United States	Research Site	Hampton	Virginia
United States	Research Site	Henderson	Nevada
United States	Research Site	Hollywood	Florida
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Hudson	Florida
United States	Research Site	Huntington Beach	California
United States	Research Site	Huntsville	Alabama
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United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Lubbock	Texas
United States	Research Site	Lufkin	Texas
United States	Research Site	Lynwood	California
United States	Research Site	Macon	Georgia
United States	Research Site	Manassas	Virginia
United States	Research Site	Marion	Ohio
United States	Research Site	McAllen	Texas
United States	Research Site	McKinney	Texas
United States	Research Site	Mechanicsville	Virginia
United States	Research Site	Melbourne	Florida
United States	Research Site	Melbourne	Florida
United States	Research Site	Memphis	Tennessee
United States	Research Site	Meridian	Idaho
United States	Research Site	Metairie	Louisiana
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Beach	Florida
United States	Research Site	Michigan City	Indiana
United States	Research Site	Middlebury	Connecticut
United States	Research Site	Midland	Michigan
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Mineola	New York
United States	Research Site	Mission Hills	California
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United States	Research Site	Modesto	California
United States	Research Site	Montgomery	Alabama
United States	Research Site	Mooresville	North Carolina
United States	Research Site	Naples	Florida
United States	Research Site	Natchitoches	Louisiana
United States	Research Site	New Bern	North Carolina
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United States	Research Site	New Orleans	Louisiana
United States	Research Site	New Port Richey	Florida
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United States	Research Site	New York	New York
United States	Research Site	Newnan	Georgia
United States	Research Site	Norfolk	Virginia
United States	Research Site	North Haven	Connecticut
United States	Research Site	North Platte	Nebraska
United States	Research Site	Northridge	California
United States	Research Site	Northridge	California
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orange	California
United States	Research Site	Orangeburg	South Carolina
United States	Research Site	Orchard Park	New York
United States	Research Site	Orlando	Florida
United States	Research Site	Oxon Hill	Maryland
United States	Research Site	Paducah	Kentucky
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Peoria	Arizona
United States	Research Site	Peoria	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Plymouth	Massachusetts
United States	Research Site	Poland	Ohio
United States	Research Site	Pontiac	Michigan
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Portland	Oregon
United States	Research Site	Portland	Oregon
United States	Research Site	Quincy	Illinois
United States	Research Site	Rancho Mirage	California
United States	Research Site	Redondo Beach	California
United States	Research Site	Richmond	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	Riverside	California
United States	Research Site	Rochester	New York
United States	Research Site	Rockport	Maine
United States	Research Site	Roseburg	Oregon
United States	Research Site	Rosedale	New York
United States	Research Site	Royal Oak	Michigan
United States	Research Site	Ruston	Louisiana
United States	Research Site	Sacramento	California
United States	Research Site	Saint Peters	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Dimas	California
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Silverdale	Washington
United States	Research Site	Southgate	Michigan
United States	Research Site	Springfield	Massachusetts
United States	Research Site	Statesville	North Carolina
United States	Research Site	Summerfield	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Tempe	Arizona
United States	Research Site	Temple	Texas
United States	Research Site	Toledo	Ohio
United States	Research Site	Toms River	New Jersey
United States	Research Site	Tulsa	Oklahoma
United States	Research Site	Voorhees	New Jersey
United States	Research Site	Washington	District of Columbia
United States	Research Site	Westminster	Colorado
United States	Research Site	Whittier	California
United States	Research Site	Whittier	California
United States	Research Site	Wichita	Kansas
United States	Research Site	Willoughby Hills	Ohio
United States	Research Site	Wilmington	North Carolina
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Yuba City	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

Toto R, Petersen J, Berns JS, Lewis EF, Tran Q, Weir MR. A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKD. J Am Soc Nephrol. 2021 Feb;32(2):469-478. doi: 10.1681/ASN.2020050556. Epub 2020 Dec 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants in Receipt of 1 or More RBC Transfusions	The percentage of participants receiving at least 1 RBC transfusion during the evaluation period was recorded for each treatment group. The evaluation period began from the date of randomization, and participants were censored at the last dose of investigational product plus 3 months or end of study, whichever was earlier (on-treatment approach).	From randomization until the end of study, up to week 101.
Secondary	Mean Number of Units of RBC Transfused	The total number of units of RBC transfused per participant during the evaluation period was recorded for each treatment group. The evaluation period began from the date of randomization, and participants were censored at the last dose of investigational product plus 3 months or end of study, whichever was earlier (on-treatment approach). The mean total number of RBC units transfused per participant is presented.	From randomization until the end of study, up to week 101.
Secondary	Time to First RBC Transfusion	Time to first RBC transfusion during the evaluation period was recorded for each treatment group. The evaluation period began from the date of randomization, and participants were censored at the last dose of investigational product plus 3 months or end of study, whichever was earlier (on-treatment approach). The time to first RBC transfusion is presented using Kaplan-Meier (KM) estimates at 6, 12, 18, and 24 months.	From randomization until the end of study, up to week 101.
Secondary	Mean Achieved Hb Concentration While Receiving Investigational Product	Average achieved Hb concentration while receiving investigational product was recorded as mean Hb using the area under the curve (AUC) method for each treatment group. The AUC of Hb was calculated according to the trapezoidal method, standardized as daily AUC. Participants with available Hb values from study day 85 (week 13) to the last dose date were included in the calculation.	From week 13 until the end of study, up to week 101.
Secondary	Geometric Mean Cumulative Dose of Darbepoetin Alfa Per 4 Weeks	Cumulative doses of darbepoetin alfa adjusted for investigation product exposure time (e.g. mean cumulative darbepoetin alfa dose per 4 weeks) were calculated for each treatment group using the total cumulative dose during the study divided by total number of weeks dosed then multiplied by 4. The geometric mean cumulative dose is presented.	From randomization until the end of study, up to week 101.

External Links

•   AmgenTrials clinical trials website