Clinical Efficacy of Two Erythropoietin Drug in Participants With Secondary Anemia to Chronic Kidney Disease.

Evaluation of Clinical Efficacy and Immunogenicity of Drug Eritromax® at Blau Farmacêutica S.A. Compared to Eprex®, Produced by Janssen-Cilag Laboratory in Participants With Secondary Anemia to Chronic Kidney Disease.

This is a prospective, randomized, multicenter, parallel, placebo-controlled, phase III study for evaluation of clinical efficacy and immunogenicity of drug Eritromax® - (rHuEPO Blau Farmacêutica S/A.) compared to Eprex® (Janssen-Cilag rHuEPO) for the treatment of patients with secondary anemia to chronic kidney disease (CKD), throughout the correction phase by assessing the change in hemoglobin levels.

Study Overview

• Status: Terminated
• Conditions: Anemia; Chronic Kidney Disease
• Intervention / Treatment: Drug: Epoetin alpha; Drug: Eprex

Detailed Description

This is a phase III study, in which participants with secondary anemia to chronic kidney disease will receive two subcutaneous injection of 50 UI/Kg of the investigational product (Eritromax®) or Eprex® per week. After four weeks of treatment, the dose of drugs will be change by clinical judged throughout study according to laboratory results. The evidence of efficacy will be evaluated by hemoglobin levels alteration throughout the correction phase (first four weeks). Secondary efficacy and safety endpoints will be assessed by: maintenance of hemoglobin levels (baseline vs. end of treatment) over maintenance phase; dose of EPO required during correction and maintenance phase; Transfusion needs; report of adverse events (including type, frequency, intensity, serioussness, severity and relation to the investigation product) throughouht 12 months of follow-up. Additionally, the immunological response of products over study will be evaluated by quantification of anti-erythropoietin every six months.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05001-000
    • CMIN - Clínica De Medicina Interna E Nefrologia
  • São Paulo, Brazil
    • Fundação Oswaldo Cruz (Hospital do Rim e Hipertensão)
  • São Paulo, Brazil
    • Real e Benemérita Associação Portuguesa de Beneficência São Paulo (Hospital Beneficência Portuguesa)
  • Bahia
    • Feira de Santana, Bahia, Brazil, 44001-584
      • Clínica Senhor do Bomfim Ltda
  • Parana
    • Curitiba, Parana, Brazil
      • Instituto Scribner de Ensino, Pesquisa, Ciência e Tecnologia
  • Rio Grande Do Sul
    • Caxias do Sul, Rio Grande Do Sul, Brazil, 95070-561
      • Fundação Universitária de Caxias do Sul - Instituto de Pesquisa Clínica para Estudos Multicêntricos
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • Irmandade da Santa Casa de Misericórdia de Porto Alegre
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil
      • Fundacao Pro-Rim
  • São Paulo
    • São Bernardo do Campo, São Paulo, Brazil
      • Hospital de Ensino Padre Anchieta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Voluntary participation and agree to all the purposes of the study by signing and dating ICF;
2. Male or female participantes, regardless of race or social class;
3. Participants aged ≥18 and ≤70 years;
4. Bearer dialysis-dependent CKD (hemodialysis and peritoneal dialysis *);
5. Clinical diagnosis of anemia, characterized as hemoglobin levels <10g/dL before the start of the study;
6. Adequate dialysis: Kt / V ≥ 1.2 for hemodialysis patients (based on the calculation of Daugirdas II) and ≥ 1.7 for patients on peritoneal dialysis;
7. Adequate iron stores (TSAT> 20% and serum ferritin> 100ng/ml) prior to initiation of treatment with erythropoietin.

Exclusion Criteria:

1. Participation in clinical trials in the 12 months preceding the survey;
2. Patients with uncontrolled hypertension, with mean above 180/100mmHg and whose requiring hospitalization in the last 6 months;
3. Presence of other causes of anemia than CKD, such as bleeding, hemolysis, pernicious anemia and hemoglobinopathies;
4. Patients who present changes or clinical abnormalities, qualified as interfering changes, such as severe hyperparathyroidism (iPTH> 1000 pg / mL), severe congestive heart failure (NYHA Class IV), acute myocardial infarction within the last 3 months, or active neoplasia in follow-up, severe liver disease, active infection (leukocyte changes), history of aluminum toxicity or scheduled surgery, pregnancy or lactation;
5. Patients who have a known hypersensitivity to any component of the formulation and to products derived from mammalian cells;
6. Prior therapies with erythropoietin for less than 3 months;
7. Realization transfusion for less than 3 months;
8. Any situation at the discretion of the Principal Investigator interfere with study data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epoetin alpha; Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eritromax), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.	Drug: Epoetin alpha; Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eritromax), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.
Active Comparator: Eprex; Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eprex), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.	Drug: Eprex; Participants assigned to this arm will receive two subcutaneous administrations per week of 50 UI/kg of Epoetin alpha (Eprex), totaling 100 UI/kg/week. After the first four weeks of treatment, once a month throughout the study the medication dose can be adjusted by the study Investigator according to the laboratory results.; Other Names: Epoetin alpha

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of hemoglobin levels at correction phase (baseline vs end of treatment)	In the correction phase, change in serum Hb levels (baseline vs. end of initial treatment (EOIT) = levels of Hb presented before the V0 treatment compared to the Hb levels presented at the end of the correction phase) will be evaluated for a maximum period of 6 months after starting treatment. This one parameter will be demonstrated through: Percentage of participants achieving Hb levels within the target (≥ 10.5 to ≤ 12 g / dL).	until 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance of hemoglobin levels	Will be evaluated by porcentage of participants whose Hb levels remained within the therapeutic range (≥10,5 a ≤ 12 g/dL).	until the end of 12 months
Adjustment of EPO dose required during correction and/or maintenance phase	Will be evaluated by mean dose of EPO used between groups and number of participants that needed of dose adjustment over correction and/or maintenance phase.	until the end of 12 months
Transfusion needs	Will be evaluated by porcentage of participants that needed of blood transfusion throughout the study.	until the end of 12 months
Report of Adverse Events	Will be evaluated by report of adverse events throughout the study. The Adverse events will be classified about the type, frequency, intensity, seriousness, severity and relation to the investigational product.	until the end of 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological Response	The immunological response induced by epoetin alpha will be evaluated by quantification of anti-erithropoetin antibodies, every six months.	every six months

Collaborators and Investigators

• Sponsor: Azidus Brasil
• Collaborators: Blau Farmaceutica S.A.
• Investigators: Study Chair: Regiane Braga, Analyst, Blau Farmaceutica S.A.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: September 26, 2012
• First Submitted That Met QC Criteria: September 27, 2012
• First Posted (Estimate): September 28, 2012

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: August 17, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; Anemia Secondary
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: EPOBLA1011; Emenda 04 - 11/May/2015 (Other Identifier: Azidus Brasil Pesquisa Científica e Desenvolvimento Ltda.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No