| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Correction of anemia in ESA-naïve patients with chronic kidney disease (CKD) who are not on dialysis. |
|
| MedDRA Classification |
| 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 |
1) To define the effective starting dose(s) for subcutaneous administration of
MK-2578 to anemic patients with CKD who are not on dialysis and who are ESA
naive.
2) To assess the safety and tolerability of subcutaneous administration of MK-2578 in patients with CKD who are not on dialysis.
|
|
| E.2.2 | Secondary objectives of the trial |
1) To determine the percentage of responders over 12 weeks (as defined by
patients achieving [pre-transfusion] an increase from baseline Hb of ≥ 1 g/dL and a
Hb concentration of ≥ 11 g/dL), the percentage of patients with at least 1 change from baseline Hb of ≥ 1 g/dL (pre-transfusion) over 12 weeks, and the percentage of
patients with at least 1 Hb value of ≥ 11 g/dL (pre-transfusion) over 12 weeks.
2) To evaluate the performance of each dose over 12 weeks, as measured by
change from baseline Hb by week; the percentage of patients requiring dose
decreases; the percentage of patients whose Hb at Week 12 is > 10 g/dL and ≤ 12 g/dL; and the percentage of patients receiving transfusions. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient is a male or female ≥ 18 and ≤ 65 years of age who weighs between 40 and 90 kg at screening Visit 1.
2. Patient is unlikely to conceive, as indicated by at least one es answer to the
following questions:
a) Patient is a male.
b) Patient is a surgically sterilized female.
c) Patient is a postmenopausal female ≥ 45 years of age with > 2 years since last
menses.
d) Patient is a non-sterilized, premenopausal female and agrees to abstain from
heterosexual activity or to use an adequate method of contraception.
Note: Acceptable methods of birth control are: hormonal contraceptive,
intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge,
condom, vasectomy.
3. Patient must meet the diagnostic criteria for chronic kidney disease as indicated by an estimated glomerular filtration rate (eGFR) between 15-60 mL/min/1.73 m2.
Note: Glomerular filtration rate is estimated using the Modification of Diet in Renal
Disease (MDRD) formula (see Appendix 6.10).
4. Patient must meet all laboratory criteria defined in Table 2-1 (See Appendix 6.1 and Appendix 6.2 for an algorithm for assessing pre-study laboratory values and a listing of all laboratory tests performed).
Note: For patients whose serum ferritin and transferrin saturation values are below
the lower limit of the inclusion ranges, iron supplementation may be started, per
center practice. If iron supplementation is initiated at screening, all screening
procedures should be delayed, including collection of Hb values used for baseline
determination. Screening procedures should subsequently be performed at least one
week after the iron dose has been stabilized over 4 weeks, per center practice. If oral iron is not sufficient to correct iron deficiency, intravenous iron may be given.
5. Patient understands the study procedures, alternative treatments available and risks involved with the study, and the patient voluntarily agrees to participate in the study by giving written informed consent. |
|
| E.4 | Principal exclusion criteria |
1. Patient is mentally or legally incapacitated, or has significant emotional problems or has a history of psychiatric disorders at the time of screening Visit 1.
2. Patient has used another ESA within 12 weeks of screening Visit 1.
3. Patient is likely to require dialysis during the study and/or is planning to have a
kidney transplant within the next 6 months.
Note: Patient may be registered for a cadaveric transplant.
4. Patient has had a blood transfusion within 12 weeks of screening Visit 1 for any reason.
5. Patient has had major surgery within the past 12 weeks or plans to have major surgery during the course of the study.
Note: Creation of a vascular access and oral surgical procedures are not considered
major surgery.
6. Patient has poorly controlled hypertension defined as systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg at screening Visit 1.
7. Patient has been on androgen therapy within 8 weeks of screening Visit 1.
8. Patient has been diagnosed with the human immunodeficiency virus.
9. Patient has a new or unexplained clinically significant abnormality on pre-study
electrocardiogram.
10. Patient has a history of blood dyscrasia, hematologic disorders (including, but not
limited to thalassemia, hemoglobinopathy, sickle cell anemia, myelodysplastic
syndromes, hematologic malignancy, hemolytic anemia, megaloblastic anemia,
thrombocytosis, iron deficiency, liver disease) or any other disease known to cause
anemia (except for CKD).
11. Patient has Class III or IV (New York Heart Association criteria) congestive heart
failure, i.e., with symptoms that occur at rest or with minimal activity (see Appendix 6.3).
12. Patient has a prolonged QTc > 480 ms on pre-study ECG.
13. Patient has a history of a malignant neoplasm, except for adequately treated nonmelanomatous skin lesions or carcinoma in situ of the cervix.
14. Patient has unstable angina or has had a thrombotic vascular event, including but not limited to myocardial infarction (MI), cerebrovascular accident (stroke, CVA),
transient ischemic attack (TIA), pulmonary embolus or deep vein thrombosis (DVT)
within 6 months of randomization.
15. Patient has a history of grand mal seizures within 6 months of randomization.
16. Patient has an active systemic infection or inflammatory disease or other conditions associated with resistance to ESAs.
17. Patient has a history of antibodies to any ESA, a history of pure red cell aplasia
(PRCA) or previous unresponsiveness to ESA.
18. Patient has a known intolerance and/or hypersensitivity to epoetin, darbepoetin alfa, and/or PEGylated products.
19. Patient has participated in a clinical study with an investigational agent within 6 weeks prior to screening Visit 1.
20. Patient is pregnant, has a positive serum pregnancy test during the screening period (prior to randomization), is expecting to conceive within the projected duration of the study or is breastfeeding.
21. Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance which in the opinion of the investigator, SPONSOR or its delegates, might pose a risk to the patient or make participation not in the patient’s best interest, that might confound the results of the study, or interfere with the patient’s participation for the full duration of the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline Hb at Week 4. |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| Consecutive double blind administration of placebo and MK-2578 |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | No |
| 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 | 10 |
| 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 | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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