E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058116 |
E.1.2 | Term | Nephrogenic anaemia |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is: • To demonstrate that AF37702 Injection can maintain hemoglobin (Hgb) in chronic renal failure subjects on hemodialysis and not yet on dialysis following conversion from darbepoetin alfa. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: • To determine the proportion of subjects who maintain a Hgb target of 10-12 g/dL following conversion from darbepoetin alfa to AF37702 Injection. • Evaluate the safety profile of AF37702 Injection in chronic renal failure subjects on hemodialysis and not yet on dialysis who were previously receiving darbepoetin alfa. The exploratory objective of this study is: • To evaluate change from baseline in patient-reported outcomes (PRO) assessment. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject eligibility is determined according to the following criteria: 1. The subject is male or female and aged 18 to 90 years, inclusive. 2. The subject is capable of understanding and complying with protocol requirements. 3. The subject or the subject’s legally authorised representative (if appropriate) signs a written, informed consent form prior to the initiation of any study procedures. 4. A female subject of childbearing potential who is sexually active agrees to use adequate contraception (as defined in the informed consent form) from screening throughout the duration of the study. 5. The subject has chronic renal failure and meets one of the following criteria: a) Has been on hemodialysis for ≥6 months prior to enrollment. b) Has not yet begun dialysis (hemodialysis or peritoneal dialysis) and is not anticipated to transition to dialysis during participation in the study. 6. The subject is on stable darbepoetin alfa maintenance therapy (either SC or IV) continuously prescribed for a minimum of 8 weeks prior to enrollment. Stability is defined as ≤50% change from the maximum prescribed weekly dose (ie, [max-min]/max ≤0.5) with no change in prescribed frequency during the last 4 weeks prior to enrollment. 7. The subject has 4 consecutive Hgb values with a mean ≥10.0 and ≤12.0 g/dL during the Screening Period, with the difference between the mean of the first 2 consecutive Hgb values and the mean of the last 2 consecutive values being ≤1.0 g/dL. Qualifying Hgb values must be taken 2 or more days between Hgb values, with maximum of 2 Hgb values within one calendar week and 9 or more days between the first and last of the 4 qualifying Hgb values. (Note: a maximum of 6 Hgb values may be obtained during a screening effort). 8. The subject has 1 ferritin level ≥100 ng/mL within 4 weeks prior to enrollment. 9. The subject has 1 serum folate level ≥ lower limit of normal within 4 weeks prior to enrollment. 10. The subject has 1 vitamin B12 level ≥ lower limit of normal within 4 weeks prior to enrollment. 11. The subject has a negative test result for hepatitis B surface antigen, and hepatitis C virus antibody at Screening and no known history of human immunodeficiency virus infection. |
|
E.4 | Principal exclusion criteria |
Any subject who meets any of the following criteria will not qualify for entry into the study: 1. If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 28 days after the end of this study; or intending to donate ova during such time period. 2. The subject has known intolerance to any ESA, all parenteral iron supplementation products, or any PEGylated molecule. 3. The subject has known bleeding or coagulation disorder. 4. The subject has known hematologic disease or cause of anemia other than renal disease (eg, PRCA, homozygous sickle-cell disease, thalassemia, multiple myeloma, hemolytic anemia and myelodysplastic syndrome). 5. The subject has had RBC or whole blood transfusion within 12 weeks prior to enrollment. 6. The subject has received a recent course of intensive iron replacement (ie, has received more than 500mg IV in the 28 days prior to enrollment). 7. The subject has poorly controlled hypertension within 4 weeks prior to enrollment, per investigator’s clinical judgment. 8. The subject has advanced chronic congestive heart failure – New York Heart Association Class III or IV. 9. The subject has uncontrolled, or symptomatic inflammatory disease (eg, rheumatoid arthritis, systemic lupus erythematosus, etc.) 10. The subject has a known history of seizure disorder or received anti-epileptic medication for seizure disorder within 6 months prior to enrollment. 11. The subject has any clinically significant medical disease or condition that, in the investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent. 12. The subject has evidence of active malignancy within past 5 years (except non-melanoma skin cancer or carcinoma-in-situ that has been completely excised). 13. The subject has a scheduled kidney transplant (Note: subjects currently on a transplant wait list are not excluded unless there is an identified donor). 14. The subject is anticipated to initiate dialysis during the course of the study (only applies to subjects who are not yet on dialysis). 15. The subject has a temporary (untunneled) dialysis access catheter (only applies to subjects receiving dialysis). 16. The subject has a scheduled surgery that may be expected to lead to significant blood loss. 17. The subject has previous exposure to any investigational agent within 4 weeks prior to enrollment, or planned receipt of an investigational agent, other than as specified by this protocol, during the study period. 18. The subject has previous exposure to AF37702 Injection. 19. The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to enrollment. 20. The subject is a study site employee, or is an immediate family member (ie, spouse, parent, child, sibling) of a study site employee, involved in conduct of this study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint • Mean change in hemoglobin between Baseline (the mean of the four most recent hemoglobin values prior to enrollment and the Hgb on the day of enrollment) and the evaluation period (mean Hgb from wks 19 to 24).
Secondary Efficacy Endpoints • Proportion of subjects who have mean Hgb values within the target range of 10.0-12.0 g/dL during the evaluation period (mean Hgb from wks 19 to 24). • Proportion of subjects with a change in Hgb between Baseline (the mean of the 4 most recent Hgb values prior to enrollment and the Hgb on the day of enrollment) and the Evaluation period (mean Hgb from wks 19 to 24) of ≤ ± 1 g/dL. • Proportion of subjects who receive red blood cell (RBC) transfusions during the Titration and Evaluation Periods. • Mean Hgb during 4-week intervals (wk 0-3, 4-7, etc.) until completion of the evaluation phase of the study. • Proportion of subjects who maintain a target Hgb of 10.0-12.0 g/dL during 4-week intervals (wk 0-3, 4-7, etc.) until completion of the evaluation phase of the study. • Proportion of subjects requiring dose adjustments during the study • Safety Endpoints: – Adverse events (AEs) and serious adverse events (SAEs). – Physical examination (including weight, vital signs, and oral temperature). – Composite safety endpoint. – Clinical laboratory tests. – Proportion of subjects with confirmed (2 consecutive values) Hgb outside the range of 10.0-12.0 g/dL. – Proportion of subjects with confirmed (2 consecutive values) Hgb values ≥12.0 g/dL, ≥13.0 g/dL, and ≥14.0 g/dL. – Proportion of subjects with Hgb increases of >1.0 g/dL in any 2-week interval during the Titration and Evaluation periods. – Proportion of subjects with Hgb increases of >2.0 g/dL in any 4-week interval during the Titration and Evaluation periods. – Incidence of AF37702-specific antibody formation.
Exploratory Endpoints: • Change from Baseline in the following patient-reported outcomes (PRO): EQ-5D, and Kidney Disease Quality of Life (KDQoL) Short Form v.1.2 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |