A Study to Evaluate the Efficacy of Converting from Intravenous or Subcutaneous rHuEPO to Intravenous Darbepoetin Alfa in Subjects with Chronic Kidney Disease Receiving Haemodialysis

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2004-004499-35-CZ
• Date of registration: 24/01/2005
• Prospective Registration: Yes
• Primary sponsor: Amgen Limited
• Public title: A Study to Evaluate the Efficacy of Converting from Intravenous or Subcutaneous rHuEPO to Intravenous Darbepoetin Alfa in Subjects with Chronic Kidney Disease Receiving Haemodialysis
• Scientific title: A Study to Evaluate the Efficacy of Converting from Intravenous or Subcutaneous rHuEPO to Intravenous Darbepoetin Alfa in Subjects with Chronic Kidney Disease Receiving Haemodialysis
• Date of first enrolment: 14/03/2005
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-004499-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Czech Republic, Hungary

Key inclusion & exclusion criteria

Inclusion criteria:
Treatment Period 1:

1. Diagnosis of CKD and receiving dialysis for at least 3 months prior to screening
2. = 18 years of age
3. Baseline Hb level = 10.0 g/dL and = 13.0 g/dL
4. Adequate iron stores (defined as serum ferritin =100 µg/L or transferrin saturation (TSAT) = 20%)
5. Stable IV (Epoetin alfa or beta) or SC rHuEPO (Epoetin beta) therapy 1, 2, or 3 times per week for at least 8 weeks before screening (stable is defined as < 25% change in weekly dose and no change in frequency or route)
6. Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1).

Treatment Period 2:

1. Completed Treatment Period 1.
2. Hb > 11.0 g/dL and = 13.0 g/dL at week 24
3. Stable QW dose of IV darbepoetin alfa during Evaluation Period 1 (weeks 21 to 24). A stable dose is defined as:
a. no prescribed dose increases, prescribed dose reductions or withheld doses
b. no more than 1 missed dose
c. no changes to dose frequency or route of administration
4. Before any protocol specific procedure for Treatment Period 2 is performed, the appropriate written informed consent must be obtained (see Section 12.1)
5. Adequate iron stores (defined as serum ferritin = 100 µg/L or TSAT = 20%) at week 24
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Treatment Period 1:

1. Received SC Epoetin alpha in the 12 months before screening
2. Uncontrolled hypertension (diastolic blood pressure > 100 mm Hg)
3. Prior history (within 12 weeks before enrolment) of cardiovascular events including:
- acute myocardial ischemia
- hospitalization for congestive heart failure
- myocardial infarction
· Pregnant or breast-feeding women. All subjects must practice adequate contraception (in the judgment of the investigator) throughout this trial.
· Treatment with an investigational agent or device within 30 days before screening or scheduled to receive an investigational agent other than those specified by this protocol during the course of this study.
· Known sensitivity to any of the products to be administered during dosing.
· Disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.

Treatment Period 2:

1. Uncontrolled hypertension (diastolic blood pressure > 100 mmHg or systolic blood pressure > 180 mmHg) on 2 separate occasions during Evaluation Period 1 (weeks 21 to 24)
2. Received a red blood cell transfusion during study weeks 16 to 24


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Anemia caused by chronic kidney didease.
MedDRA version: 6.1 Level: PT Classification code 10038444

Intervention(s)

Trade Name: Aranesp
Product Name: Darbepoetin Alfa 10 µg/0.4 ml Prefilled Syringe
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Darbepoetin Alfa
Other descriptive name: 10 µg/0.4 ml Prefilled Syringe
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Aranesp
Product Name: Darbepoetin Alfa 15 µg/0.375 ml Prefilled Syringe
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Darbepoetin Alfa
Other descriptive name: 15 µg/0.375 ml Prefilled Syringe
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Trade Name: Aranesp
Product Name: Darbepoetin Alfa 20 µg/0.5 ml Prefilled Syringe
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Darbepoetin Alfa
Other descriptive name: 20 µg/0.5 ml Prefilled Syringe
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Trade Name: Aranesp
Product Name: Darbepoetin Alfa 30 µg/0.3 ml Prefilled Syringe
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Darbepoetin Alfa
Other descriptive name: 30 µg/0.3 ml Prefilled Syringe
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Aranesp
Product Name: Darbepoetin Alfa 40 µg/0.4 ml Prefilled Syringe
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Darbepoetin Alfa
Other descriptive name: 40 µg/0.4 ml Prefilled Syringe
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Aranesp
Product Name: Darbepoetin Alfa 50 µg/0.5 ml Prefilled Syringe
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Darbepoetin Alfa
Other descriptive name: 50 µg/0.5 ml Prefilled Syringe
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: Aranesp
Product Name: Darbepoetin Alfa 60 µg/0.3

Primary Outcome(s)

Primary end point(s): Primary Efficacy Endpoint

Treatment Period 1:

• Mean Hb during the evaluation period (weeks 21-24)

Treatment Period 2:

• Mean Hb level during Evaluation Period 2 (weeks 45-48)

Secondary Efficacy Endpoints

Treatment Period 1:

• The proportion of subjects with a mean Hb > 11.0 g/dL during the evaluation period
• Change in Hb between screening/baseline and the evaluation period
• Dose and frequency of darbepoetin alfa administration during the treatment period

Treatment Period 2:

• The proportion of subjects with a mean Hb > 11.0 g/dL during Evaluation Period 2
• Change in Hb between Evaluation Period 1 (as baseline for Treatment Period 2) and Evaluation Period 2
• The proportion of subjects with a change in Hb between Evaluation Period 1 (as baseline for Treatment Period 2) and Evaluation Period 2 within the inclusive range -1.0 to +1.5 g/dL
• Dose and frequency of darbepoetin alfa administration during the treatment period

Exploratory Endpoints

Treatment Period 1:

• The proportion of subjects with a mean Hb > 11.0 g/dL and = 13.0 g/dL during the evaluation period
• The proportion of subjects with a baseline Hb = 11.0 g/dL that achieve a mean Hb > 11.0 g/dL during the evaluation period with no increases in darbepoetin alfa dose or dose frequency during weeks 1 to 24

Treatment Period 2:

• The proportion of subjects with a mean Hb > 11.0 g/dL and = 13.0 g/dL during Evaluation Period 2

Safety Endpoints

Treatment Periods 1 and 2 separately

• Subject incidence and severity of adverse events
• Subject incidence of RBC transfusions during the study
• Laboratory parameters and vital signs

Secondary Objective: Treatment Period 1:

· To evaluate the overall proportion of subjects achieving treatment targets for haemoglobin
· To evaluate the proportion of subjects achieving treatment targets for haemoglobin in the sub-group of patients with a baseline Hb level = 11.0g/dL.
· To assess the safety of switching patients to IV darbepoetin alfa by measurement of adverse events and laboratory parameters.

Treatment Period 2:

• To determine the proportion of subjects with a mean Hb > 11 g/dL
• To determine the mean change in Hb between Evaluation Period 1 (weeks 21 to 4) and Evaluation Period 2 (weeks 45 to 48)
• To determine the proportion of subjects with a mean Hb level maintained within -1.0 to +1.5 g/dL of the Hb in Evaluation Period 1
• To assess the safety of darbepoetin alfa once every two weeks by measurement of adverse events and laboratory parameters

Main Objective: Treatment Period 1:

To demonstrate that haemoglobin (Hb) levels can be maintained or increased after switching HD subjects from either subcutaneous (SC) or intravenous (IV) rHuEPO to IV darbepoetin alfa.

Treatment Period 2:

To demonstrate that switching subjects with a Hb > 11 g/dL and = 13 g/dL from once weekly IV darbepoetin alfa to once every 2 weeks (Q2W) maintains the mean Hb at > 11 g/dL.

Secondary ID(s)

20040218