Paroxysmal Nocturnal Hemoglobinuria (PNH) MedDRA version: 20.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857
Conditions
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The study will enroll subjects with PNH who are stable on eculizumab treatment. Subjects cannot be enrolled or randomized before all inclusion criteria (including test results) are confirmed: 1. Men and women = 18 years of age 2. Historical diagnosis of PNH by documented flow cytometry 3. Administration of eculizumab for = 6 months and currently receiving 900 mg of eculizumab every 14 ± 2 days 4. Hemoglobin = 9.0 g/dL for at least 6 weeks prior to randomization 5. Lactate dehydrogenase (LDH) =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: If any of the following apply, the subject MUST NOT enter the study: 1. Known or suspected hereditary complement deficiency 2. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure [New York Heart Association = Class III], serious uncontrolled cardiac arrhythmia), peripheral vascular disease, cerebrovascular accident, or transient ischemic attack in the previous 6 months 3. Evidence of acute thrombosis (liver Doppler ultrasound of hepatic and portal veins) 4. Known to be positive for human immunodeficiency virus 5. Woman who is pregnant or breastfeeding 6. Woman of childbearing potential who does not consent to use a highly effective method of birth control (e.g., true abstinence, sterilization, birth control pills, Depo Provera injections, or contraceptive implants) during treatment and for an additional 5 months after the last administration of protocol-specified treatment 7. Man with a partner of childbearing potential who does not consent to use a highly effective method of birth control (eg, true abstinence, vasectomy, or a condom in combination with hormonal birth control or barrier methods used by the woman) during treatment and for an additional 5 months after the last administration of protocol-specified treatment 8. Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s). 9. Subject has known sensitivity to any constituent of the products to be administered during the study, including mammalian cell-derived drug products. 10. History or evidence of clinically significant disorder, infection, condition, or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. 11. History of meningococcal infection 12. Presence or suspicion of active bacterial infection, or recurrent bacterial infection. 13. History of bone marrow transplantation 14. Red blood cell transfusion required within 12 weeks before randomization 15. Subject experienced = 2 breakthrough events, (ie, signs and symptoms of intravascular hemolysis, that require dose and/or schedule adjustments of eculizumab) in the previous 12 months before screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective for this study is to evaluate the efficacy of ABP 959 compared with that of eculizumab based on control of intravascular hemolysis.; Secondary Objective: The secondary objective is to assess the safety, pharmacokinetics (PK), and immunogenicity of ABP 959 compared with that of eculizumab. ; Primary end point(s): Primary Endpoint for Parallel Comparison: • Hemolysis, as measured by LDH at week 27 Primary Endpoint for Crossover Comparison: • Hemolysis, as measured by the time-adjusted AUEC of LDH from week 39 to 53 and from week 65 to 79 ; Timepoint(s) of evaluation of this end point: The primary analysis of the primary endpoint of week 27 LDH for the parallel comparison will be conducted on the Full Analysis Set (FAS), consisting of all randomized subjects, with treatment as randomized in Period 1 regardless of treatment actually received. The primary analysis of the primary endpoint of time-adjusted AUEC of LDH for the crossover comparison will be conducted on the Modified Full Analysis Set (mFAS), consisting of all randomized subjects who have an LDH-time profile evaluable for the time-adjusted AUEC within weeks 39 to 53 and/or within weeks 65 to 79, according to treatment per the randomized sequence regardless of treatment actually received. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Total complement (CH50), total hemoglobin, serum-free hemoglobin, haptoglobin, bilirubin, degree of hemoglobinuria, and type III erythrocytes at week 27, week 39, week 53, and post-crossover week 65 and week 79 • Crossover comparison of hemolysis as measured by LDH at week 53 and week 79 • Lactate dehydrogenase-time profile • Red blood cell transfusion • Pharmacokinetic area under the curve (AUC) of ABP 959 and eculizumab from week 13 to 15, and trough PK ; Timepoint(s) of evaluation of this end point: The analysis of secondary endpoints (except for PK) will be conducted on the FAS. Total complement, total hemoglobin, serum-free hemoglobin, haptoglobin, bilirubin, degree of hemoglobinuria, and type III erythrocytes (%) at weeks 27, 39, 53, 65, and 79 will be summarized descriptively. For the endpoint of RBC transfusions, summary statistics for the number of packed red cells transfused per month after week 13 will be presented. A descriptive summary of LDH at each time point through the end of the study (EOS) visit will be presented. Individual and mean LDH-time profile through EOS visit will also be presented graphically. The secondary endpoint of crossover comparison of LDH at week 53 and week 79 will be evaluated descriptively. | — |
Countries
Czech Republic, France, Germany, Ireland, Italy, Netherlands, Norway, Slovenia, Spain, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed