E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anemia in CKD patients not on dialysis |
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E.1.1.1 | Medical condition in easily understood language |
Anemia in patients with chronic kidney disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002272 |
E.1.2 | Term | Anemia |
E.1.2 | System Organ Class | 100000004851 |
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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 |
To evaluate the efficacy of roxadustat in the treatment of anemia in non-dialysis Chronic Kidney Disease (CKD) subjects. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety of roxadustat.
- To evaluate health-related quality of life benefit.
- To evaluate the need for rescue therapy. (RBC transfusion, ESA, or IV Iron) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject is eligible for the study if all of the following apply:
- Age ≥ 18 years
- Diagnosis of chronic kidney disease, with Kidney Disease Outcomes
Quality Initiative (KDOQI) Stage 3, 4 or 5, not receiving dialysis; with
an eGFR <60 mL/min/1.73 m2 estimated using the abbreviated 4-
variable Modification of Diet in Renal Disease (MDRD) equation.
- Mean of the three most recent Hb values during the Screening period,
obtained at least 4 days apart, must be ≤10.0 g/dL, with a difference of
≤1.0 g/dL between the highest and the lowest values.
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3
x upper limit of normal (ULN), and total bilirubin (TBL) ≤1.5 x ULN.
- Body weight of 45.0 kg up to a maximum of 160.0 kg. |
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E.4 | Principal exclusion criteria |
Subject will be excluded from participation if any of the following apply:
- Any ESA treatment within 12 weeks prior to randomization.
- More than one dose of IV iron within 12 weeks prior to randomization.
- RBC transfusion within 8 weeks prior to randomization.
- chronic inflammatory disease that could impact erythropoiesis even if it is currently in remission.
- myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., pulmonary embolism) within 12 weeks prior to randomization.
- two or more blood pressure values of systolic BP (SBP) ≥ 160 mmHg or diastolic BP (DPB) ≥ 95 mmHg confirmed by repeat measurement within 2 weeks prior to randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. The EU (EMA) primary efficacy endpoint is Hb response.
Hb response is defined as:
•Hb ≥ 11.0 g/dL and a Hb increase from BL by ≥ 1.0 g/dL in any subject with BL Hb > 8.0 g/dL, OR
•an increase from BL by ≥ 2.0 g/dL in any subject with BL Hb ≤ 8.0 g/dL
at two consecutive visits separated by at least 5 days during the first 24 weeks of treatment without rescue therapy (i.e., RBC transfusion, ESA, or IV iron) prior to Hb response.
2. The US (FDA) primary efficacy endpoint is the change in Hb from baseline to the average level during the evaluation period (defined as Week 28 until Week 52) regardless of rescue therapy.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to and including week 24 |
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E.5.2 | Secondary end point(s) |
•Hb maintenance: Hb change from BL to the average Hb of weeks 28-36, without having received rescue therapy within 6 weeks prior to and during this 8-week evaluation period.
•Change from BL in Low–density Lipoprotein (LDL) cholesterol to the average LDL cholesterol in weeks 12-28.
•Blood pressure effect
•Change from BL in Mean Arterial Pressure (MAP) to the average MAP in weeks 20-28.
•Occurrence, and time to occurrence of hypertension (defined as either SBP >170 mmHg AND an increase from BL ≥ 20 mmHg or as DBP > 110 mmHg, AND an increase from BL ≥ 15 mmHg on 2 consecutive visits).
•Use and time to use of rescue therapy (composite of RBC transfusions, ESA use, and IV iron) in the first 24 weeks of treatment.
•Change from BL in SF-36 Physical Functioning (PF) subscore to the average SF-36 PF subscore in weeks 12-28.
•Change from BL in SF-36 Vitality (VT) subscore to the average SF-36 VT subscore in weeks 12-28.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 93 |
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 | No |
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 |
Belgium |
Bulgaria |
Colombia |
Dominican Republic |
Estonia |
Georgia |
Greece |
Guatemala |
Hungary |
Italy |
Panama |
Peru |
Poland |
Romania |
Russian Federation |
Serbia |
South Africa |
Spain |
Turkey |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |