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Phase III, multicenter, randomized, open, controlled clinical trial. A study designed as phase III, in 120 patients with chronic renal failure in the pre-dialysis stage, evaluate efficacy and safety of Hemax PFS® (PFS: prefilled syringes) vs the innovator erythropoietin alfa product (Eprex®).
This was a Phase IIIB, multicenter, randomized, open-label study to compare two products with epoetin alfa (HEMAX® PFS versus EPREX/ERYPO®).
This trial was open-label for both the patient and the investigator, but blinded in the performance of laboratory analyses.
The overall objective of the study was to evaluate the efficacy and the safety of HEMAX® PFS compared to EPREX/ERYPO®, following a dose-titration and maintenance scheme similar to the one used in the regular clinical practice.
All patients received HEMAX® PFS or EPREX/ERYPO® twice a week subcutaneously during 12 weeks of titration, switching then to an equivalent weekly dose during 12 additional maintenance weeks. During the dosing scheme switch from twice a week to once weekly, each patient continued receiving the treatment assigned at randomization.
The study conclude with n=43 patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eprex/Erypo | Active Comparator | Receive EPREX/ ERYPO® subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks. |
|
| Hemax PFS | Experimental | receive HEMAX® PFS subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Erythropoietin alfa | Biological | Prefilled syringes of erythropoietin |
|
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy Evaluation Through Change in Hemoglobin Levels | Evaluate the efficacy of treatment with erythropoietin alfa through the measured changes in levels of hemoglobin from baseline value to the mean value of the 8 to 12 weeks of treatment, comparing patients treated with HEMAX® PFS versus EPREX/ ERYPO®. | 12 weeks of treatment |
| Adverse Events and Adverse Reactions (Safety and Tolerability) at Weeks 12 and 24. | Evaluate the safety through the incidence of adverse events and adverse reactions asessed after 12 and 24 weeks of treatment (week 24 reported which includes those evaluated at week 12), comparing patients treated with HEMAX® PFS versus those treated with EPREX/ ERYPO®. | 24 weeks of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Responder Patients | Evaluate the efficacy of treatment with erythropoietin alfa through the percentage of responder patients (increase of Hb ≥ 1g/ dl) after 12 weeks of treatment, comparing patients treated with HEMAX® PFS versus those treated with EPREX/ ERYPO®. | 12 weeks of treatment |
| Percentage of Patients That Required Any Transfusion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Diego Ambrogetti, MD | Instituto de Investigaciones médicas Alfredo Lanari | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CEMEDIC | Buenos Aires | Argentina | ||||
| CEREHA |
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| ID | Title | Description |
|---|---|---|
| FG000 | Eprex/Erypo | Receive EPREX/ ERYPO® subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks. Erythropoietin alfa: Prefilled syringes of erythropoietin |
| FG001 | Hemax PFS | receive HEMAX® PFS subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks. Erythropoietin alfa: Prefilled syringes of erythropoietin |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Eprex/Erypo | Receive EPREX/ ERYPO® subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks. Erythropoietin alfa: Prefilled syringes of erythropoietin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Efficacy Evaluation Through Change in Hemoglobin Levels | Evaluate the efficacy of treatment with erythropoietin alfa through the measured changes in levels of hemoglobin from baseline value to the mean value of the 8 to 12 weeks of treatment, comparing patients treated with HEMAX® PFS versus EPREX/ ERYPO®. | Per protocol analysis | Posted | Mean | Standard Deviation | Hemoglobin levels (g/dL) | 12 weeks of treatment |
|
After 12 and 24 weeks of treatment
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Eprex/Erypo | Receive EPREX/ ERYPO® subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks. Erythropoietin alfa: Prefilled syringes of erythropoietin |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sepsis | Infections and infestations | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Increased blood pressure | Cardiac disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director of Clinical Trials | Biosidus S.A.U. | +541149098044 | v.berstein@biosidus.com.ar |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 26, 2018 | Nov 1, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 31, 2022 | Nov 12, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000740 | Anemia |
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
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Evaluate the percentage of transfusional requirements after 12 weeks of treatment, comparing patients treated with HEMAX PFS versus those treated with EPREX/ ERYPO®. |
| 12 weeks of treatment |
| Change of Hemoglobin Level at Week 12 of Treatment | Evaluate the efficacy between arms (HEMAX® PFS and EPREX/ ERYPO®) of treatment with erythropoietin alfa through the change in the level of hemoglobin from baseline in every visit until the week 12 visit. | Intragroup efficacy until week 12 |
| Evaluate the Efficacy Between Arms 24 Weeks: Week Doses in the Titration | Evaluate the efficacy between arms (HEMAX® PFS and EPREX/ ERYPO®) of the change from the twice - a - week doses in the titration phase to a weekly dose in the maintenance phase through the changes in the hemoglobin levels from week 12 to weeks 16, 20 and 24 of treatment | Intragroup efficacy until week 24 |
| Incidence of Anti-drug Antibodies (Immunogenicity) | An anti-erythropoietin alfa antibody determination will be performed to evaluate treatment immunogenicity at week 12 and 24 visit | 12 and 24 weeks of treatment |
| Concentration of Hepcidin | Hepcidin will be analyzed by ELISA at baseline, week 12 and 24 in order to evaluate the treatment response. | 24 weeks of treatment |
| Buenos Aires |
| Argentina |
| CIMEL | Buenos Aires | Argentina |
| CIPREC (Centro de Investigación y Prevención Cardiovascular) | CABA | Argentina |
| GEMA Consultorio | Caba | Argentina |
| Hospital Argerich | CABA | Argentina |
| Hospital Británico de Buenos Aires | CABA | Argentina |
| Hospital Durand | CABA | Argentina |
| Hospital Fernandez | CABA | Argentina |
| Hospital Ramos Mejía | CABA | Argentina |
| IPHIC | Asunción | Paraguay |
| BG001 | Hemax PFS | Receive HEMAX® PFS subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks. Erythropoietin alfa: Prefilled syringes of erythropoietin |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Hemoglobin blood level | Three patients from the HEMAX group and four patients from the EPREX group did not complete the study procedures. | Mean | Standard Deviation | g/dL |
|
| OG001 | Hemax PFS | Receive HEMAX® PFS subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks. Erythropoietin alfa: Prefilled syringes of erythropoietin |
|
|
| Primary | Adverse Events and Adverse Reactions (Safety and Tolerability) at Weeks 12 and 24. | Evaluate the safety through the incidence of adverse events and adverse reactions asessed after 12 and 24 weeks of treatment (week 24 reported which includes those evaluated at week 12), comparing patients treated with HEMAX® PFS versus those treated with EPREX/ ERYPO®. | Posted | Number | Adverse Events | 24 weeks of treatment |
|
|
|
| Secondary | Percentage of Responder Patients | Evaluate the efficacy of treatment with erythropoietin alfa through the percentage of responder patients (increase of Hb ≥ 1g/ dl) after 12 weeks of treatment, comparing patients treated with HEMAX® PFS versus those treated with EPREX/ ERYPO®. | Patients were classified as non-responders when hemoglobin did not increase at least 1 g/dL regarding baseline during any of the first 12 weeks of treatment | Posted | Number | percentage of participants | 12 weeks of treatment |
|
|
|
| Secondary | Percentage of Patients That Required Any Transfusion | Evaluate the percentage of transfusional requirements after 12 weeks of treatment, comparing patients treated with HEMAX PFS versus those treated with EPREX/ ERYPO®. | Posted | Number | Percentage of patients | 12 weeks of treatment |
|
|
|
| Secondary | Change of Hemoglobin Level at Week 12 of Treatment | Evaluate the efficacy between arms (HEMAX® PFS and EPREX/ ERYPO®) of treatment with erythropoietin alfa through the change in the level of hemoglobin from baseline in every visit until the week 12 visit. | Posted | Mean | Standard Deviation | Hemoglobin levels (g/dL) | Intragroup efficacy until week 12 |
|
|
|
| Secondary | Evaluate the Efficacy Between Arms 24 Weeks: Week Doses in the Titration | Evaluate the efficacy between arms (HEMAX® PFS and EPREX/ ERYPO®) of the change from the twice - a - week doses in the titration phase to a weekly dose in the maintenance phase through the changes in the hemoglobin levels from week 12 to weeks 16, 20 and 24 of treatment | Posted | Mean | Standard Deviation | Hemoglobin levels (g/dL) | Intragroup efficacy until week 24 |
|
|
|
| Secondary | Incidence of Anti-drug Antibodies (Immunogenicity) | An anti-erythropoietin alfa antibody determination will be performed to evaluate treatment immunogenicity at week 12 and 24 visit | Posted | Number | Participants with positive result | 12 and 24 weeks of treatment |
|
|
|
| Secondary | Concentration of Hepcidin | Hepcidin will be analyzed by ELISA at baseline, week 12 and 24 in order to evaluate the treatment response. | The analysis was restricted to patients with available hepcidin samples at baseline, 12 weeks, and 24 weeks due to an unanticipated loss of samples. | Posted | Mean | Standard Deviation | ng hepcidin/ml | 24 weeks of treatment |
|
|
|
| 1 |
| 20 |
| 4 |
| 20 |
| 8 |
| 20 |
| EG001 | Hemax PFS | receive HEMAX® PFS subcutaneously with an initial dose of 29 IU/ kg twice a week (2000 IU twice a week for 70 kg of weight), to be titrated according to the scheme that is summarized below. There will be a follow - up of patients with visits to the site every two weeks during the first 12 weeks of dose titration that will be followed by 12 additional weeks of dose maintenance with visits every 4 weeks. Erythropoietin alfa: Prefilled syringes of erythropoietin | 0 | 23 | 3 | 23 | 5 | 23 |
| Gastrointestinal angiodysplasia | Gastrointestinal disorders | Non-systematic Assessment |
|
| Worsening of renal function | Renal and urinary disorders | Non-systematic Assessment |
|
| Urinary tract infection | Renal and urinary disorders | Non-systematic Assessment |
|
| Foot ulcer | Vascular disorders | Non-systematic Assessment |
|
| Worsened condition | General disorders | Non-systematic Assessment | Generalized implication syndrome, asthenia, frequent falls due to ambulatory difficulties, reason for which she was hospitalized. |
|
| Lower limb edema | Cardiac disorders | Non-systematic Assessment |
|
| Hypervolemia | Cardiac disorders | Non-systematic Assessment |
|
| Hypotension | Cardiac disorders | Non-systematic Assessment |
|
| Acute diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | Non-systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Acute gastroenteritis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Splenomegaly | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Increased lipids | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Increased creatinine levels | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Increased potassium levels | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypovitaminosis D | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Acute bronchitis | Infections and infestations | Non-systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | Non-systematic Assessment |
|
| Conjunctivitis | Infections and infestations | Non-systematic Assessment |
|
| COVID-19 | Infections and infestations | Non-systematic Assessment |
|
| Scabies | Infections and infestations | Non-systematic Assessment |
|
| Knee arthropathy | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Cervical pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Heel pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Insomnia | Nervous system disorders | Non-systematic Assessment |
|
| Renal cyst | Renal and urinary disorders | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Increased body weight | General disorders | Non-systematic Assessment |
|
| Pruritus | General disorders | Non-systematic Assessment |
|
| Venous ulcer | Vascular disorders | Non-systematic Assessment |
|
| Peripheral arterial disease | Vascular disorders | Non-systematic Assessment |
|
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| D014570 |
| Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Unknown or Not Reported |
|
| Change |
|
| Week 20 |
|
| Week 24 |
|
| Week 24 |
|