A Phase 3, Long-Term Safety Study of Subcutaneous Epoetin Hospira in Patients With Chronic Renal Failure Requiring Hemodialysis and Receiving Epoetin Maintenance Treatment. AiME -Anemia Management With Epoetin (AiME - 04)

• ClinicalTrials.gov Identifier: NCT01628120
• Recruitment Status: Completed
• First Posted: June 26, 2012
• Results First Posted: July 19, 2018
• Last Update Posted: March 18, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: June 22, 2012
• First Posted Date: June 26, 2012
• Results First Submitted Date: May 21, 2018
• Results First Posted Date: July 19, 2018
• Last Update Posted Date: March 18, 2019
• Actual Study Start Date: May 31, 2012
• Actual Primary Completion Date: February 13, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 22, 2018)

• Percentage of Participants With Treatment Emergent Adverse Events (AEs): Week 1 [ Time Frame: Up through 7 days after first dose of study drug (Week 1) ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.
• Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 1 to 12 [ Time Frame: Week 1 up to Week 12 ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.
• Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 13 to 24 [ Time Frame: Week 13 up to Week 24 ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.
• Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 25 to 36 [ Time Frame: Week 25 up to Week 36 ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.
• Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 37 to 48 [ Time Frame: Week 37 up to Week 48 ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.
• Percentage of Participants With Treatment Emergent Adverse Events (AEs): Over Week 1 to 48 [ Time Frame: Week 1 up to Week 48 ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment emergent are events that emerged during the treatment period and were absent before treatment or that worsened relative to pretreatment state.

Original Primary Outcome Measures (submitted: June 22, 2012)

Treatment emergent adverse events [ Time Frame: 48 weeks ]

The percentage of patients with TEAEs every 7 days from the date of the first dose, each 12 week period, and the last day of the Treatment Period

Current Secondary Outcome Measures (submitted: June 22, 2018)

• Mean Weekly Dosage of Epoetin Hospira: Over Week 1 to 48 [ Time Frame: Week 1 up to Week 48 ]
• Mean Weekly Dosage of Epoetin Hospira for Interval of 12 Weeks [ Time Frame: Week 1 up to Week 12; Week 13 up to Week 24; Week 25 up to Week 36; Week 37 up to Week 48 ]
• Mean Hemoglobin Levels: Over Week 1 to 48 [ Time Frame: Week 1 up to Week 48 ]
• Mean Hemoglobin Levels for Interval of 12 Weeks [ Time Frame: Week 1 up to Week 12; Week 13 up to Week 24; Week 25 up to Week 36; Week 37 up to Week 48 ]
• Mean Hematocrit Levels: Over Week 1 to 48 [ Time Frame: Week 1 up to Week 48 ]
  Hematocrit is defined as the percentage of red blood cells in the blood.
• Mean Hematocrit Levels for Interval of 12 Weeks [ Time Frame: Week 1 up to Week 12; Week 13 up to Week 24; Week 25 up to Week 36; Week 37 up to Week 48 ]
  Hematocrit is defined as the percentage of red blood cells in the blood.
• Percentage of Participants With Hemoglobin Level Outside Target Range [ Time Frame: Week 1 up to Week 48 ]
  Percentage of participants with hemoglobin level outside the target range of 9.0 to 11.0 g/dL were reported.
• Percentage of Participants Who Received Blood Transfusions [ Time Frame: Week 1 up to Week 48 ]

Original Secondary Outcome Measures (submitted: June 22, 2012)

• Mean weekly epoetin dosage [ Time Frame: 48 weeks ]
  Mean weekly epoetin dosage per kg body weight over 48 weeks and for each 12 week period
• Mean hemoglobin levels [ Time Frame: 48 weeks ]
  Mean Hb levels over 48 weeks and for each 12 week period
• Mean hematocrit levels [ Time Frame: 48 weeks ]
  Mean hematocrit (Hct) levels over 48 weeks and for each 12 week period

Current Other Pre-specified Outcome Measures (submitted: June 22, 2018)

• Percentage of Participants With Hemoglobin Level Less Than (<) 8.0 Gram Per Deciliter (g/dL) [ Time Frame: Week 1 up to Week 48 ]
• Percentage of Participants With Hemoglobin Level Greater Than (>) 12.0 Gram Per Deciliter (g/dL) [ Time Frame: Week 1 up to Week 48 ]
• Number of Participants With Clinically Significant Change From Baseline in Hemoglobin (Hb) Levels [ Time Frame: Baseline up to Week 48 ]
  Participants with clinically significant change from baseline in hemoglobin levels were upon investigator's discretion.
• Number of Participants Who Received Concomitant Medication [ Time Frame: Week 1 up to Week 48 ]
• Number of Participants With Clinically Significant Change From Baseline in Laboratory Tests [ Time Frame: Baseline up to Week 48 ]
  Laboratory tests included: Hematology (hematocrit, hemoglobin, red blood cells count, reticulocytes, white blood cells count, neutrophils, bands, lymphocytes, monocytes, basophils, eosinophils, platelets, mean corpuscular volume); Coagulation panel (prothrombin time, international normalized ratio, activated partial thromboplastin time); Chemistry (blood urine nitrogen, creatinine, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, calcium, gamma-glutyl transpeptidase, phosphorus, uric acid, total protein, glucose, albumin, C-reactive protein); iron status (plasma ferritin, transferrin saturation). Participants with clinically significant change from baseline in laboratory tests were based on investigator's discretion.
• Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiogram (ECG) [ Time Frame: Baseline up to Week 48 ]
  ECG parameters included: PR interval, QRS complex, QT interval and QTC interval. Participants with clinically significant change from baseline in 12-lead ECGs were based on investigator's discretion.
• Number of Participants With Clinically Significant Change From Baseline in Physical Examinations [ Time Frame: Baseline up to Week 48 ]
  Physical examination included examination of the skin, eyes, ears, throat, neck, and cardiac, respiratory, gastrointestinal and musculoskeletal systems. The examination assessed the participants for any clinically significant changes in physical status, as determined by the investigator.
• Percentage of Participants With Anti-Recombinant Human Erythropoietin (rhEPO) Antibodies [ Time Frame: Baseline, Week 48 ]
  Percentage of participants with at least 1 positive anti-rhEPO antibodies were reported. Radioimmunoprecipitation assay method was used to determine the presence of anti-rhEPO antibodies.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 3, Long-Term Safety Study of Subcutaneous Epoetin Hospira in Patients With Chronic Renal Failure Requiring Hemodialysis and Receiving Epoetin Maintenance Treatment. AiME -Anemia Management With Epoetin
• Official Title: A Phase 3, Open-label, Multicenter, Long-term Safety Study Of Subcutaneous Epoetin Hospira In Patients With Chronic Renal Failure Requiring Hemodialysis And Receiving Epoetin Maintenance Treatment
• Brief Summary: To determine the long term safety in treatment-emergent adverse events (TEAEs) of SC administration of Epoetin Hospira for maintenance of target hemoglobin (Hgb) levels in patients treated for anemia associated with chronic renal failure and on hemodialysis.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Renal Failure Requiring Hemodialysis

Intervention

Biological: Epoetin Hospira

Subcutaneous(SC) injection

Other Names:

• ESA
• Erythropoetin Stimulation Agents

Study Arms

Experimental: Epoetin Hospira

Epoetin Hospira will be administered by SC bolus injection 1 to 3 times per week per each patient's dosing schedule. Other ESAs (except for long-acting) may be used as rescue therapy.

Intervention: Biological: Epoetin Hospira

• Publications *: Wish JB, Rocha MG, Martin NE, Reyes CRD, Fishbane S, Smith MT, Nassar G. Long-term Safety of Epoetin Alfa-epbx for the Treatment of Anemia in ESKD: Pooled Analyses of Randomized and Open-label Studies. Kidney Med. 2019 Aug 28;1(5):271-280. doi: 10.1016/j.xkme.2019.06.009. eCollection 2019 Sep-Oct.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 22, 2018): 170
• Original Estimated Enrollment (submitted: June 22, 2012): 288
• Actual Study Completion Date: February 13, 2015
• Actual Primary Completion Date: February 13, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patient is able to provide written Informed Consent after the risks and benefits of the study have been explained prior to any study related activities.
2. Patient previously completed the core study Maintenance Period up to and including Week 16 study assessments per protocol and is willing to continue open-label Epoetin Hospira for up to 48 weeks.

3. If female, patient must be postmenopausal for at least 1 year prior to enrollment, surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or practicing at least 1 of the following methods of birth control:

   • hormonal contraceptives (oral, parenteral, or transdermal) for at least 3 months prior to enrollment
   • intrauterine device
   • double-barrier method (condoms, contraceptive sponge, diaphragm, or vaginal ring with spermicidal jellies or cream)

   If hormonal contraceptives are used, the specific contraceptive must have been used for at least 3 months prior to enrollment. If the patient is currently using a hormonal contraceptive, she should also use a barrier method during this study and for at least 30 days following the administration of the patient's last open-label dose.

4. Adequate methods of contraception to prevent pregnancy are to be maintained throughout the course of the study in both male and female study subjects.

Exclusion Criteria:

1. Patient had a serious or severe adverse event in the core study that, in the opinion of the Investigator, was probably or definitely related to epoetin use and precluded safe use of epoetin.

2. Any of the following that developed during the core study and prior to enrollment:

   • Myocardial infarction
   • Stroke (cerebrovascular accident)/cerebrovascular insult (minor stroke) or transient ischemic attack/intracerebral bleeding/cerebral infarction
   • Severe/unstable angina
   • Coronary angioplasty, bypass surgery, or peripheral artery bypass graft
   • Decompensated congestive heart failure (New York Heart Association [NYHA] class IV)
   • Pulmonary embolism
   • Deep vein thrombosis or other thromboembolic event
   • Received live or attenuated vaccination (except flu vaccination)
3. A patient with any active, uncontrolled systemic, inflammatory, or malignant disease that developed during the core study and in the Investigator's opinion may be significant to exclude participation in the study, including but not limited to demyelinating diseases such as multiple sclerosis, microbial, viral, or fungal infection or mental disease.
4. Any newly developed significant drug sensitivity or a significant allergic reaction to any drug, as well as known hypersensitivity or idiosyncratic reaction to epoetin (or its excipients, including albumin) or any other related drugs that in the judgment of the Investigator is exclusionary for study participation.
5. A female patient who is pregnant, lactating, or planning a pregnancy during the study.
6. History of drug abuse or alcohol abuse during the core study prior to enrollment as determined by the Investigator.
7. Current participation or participation in a drug or other investigational research study within 30 days prior to enrollment (except the core study or any observational studies with prior written approval from Hospira).
8. May not be able to comply with the requirements of this clinical study, communicate effectively with study personnel, or is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
9. Evidence of human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg).
10. A patient who, in the Investigator's opinion, has any clinically significant abnormal laboratory results that may impact patient safety.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01628120
• Other Study ID Numbers: EPOE-11-04; C3461005 ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: February 2019