| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Hyperphosphataemia in patients with Chronic Kidney Disease (CKD) on hemodialysis |
|
| 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 | 10020712 |
| E.1.2 | Term | Hyperphosphatemia |
|
| 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 |
This study is designed to demonstrate superior or at least non-inferior
efficacy of SBR759 in phoshate binding, versus sevelamer HCl and evaluate safety over a long term exposure. Efficacy will be measured by the number of patients with a serum phosphate level below or equal to 5.5 mg/dl (i.e. 1.78 mmol/L) at 12 weeks |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate safety and tolerability of SBR759 compared to sevelamer HCl over a 12-week period.
To evaluate whether SBR759 has superior efficacy at week 12 compared to sevelamer HCl, as measured by the number of patients with a serum calcium-phosphate product levels below or equal to 55 mg2/dL2.
To evaluate whether SBR759 is associated with less increase in serum iPTH levels compared to sevelamer HCl at 12 weeks.
To evaluate whether SBR759 has an equivalent rate of hypercalcemia events at 12 weeks compared to sevelamer HCl as measured by serum calcium levels.
To evaluate changes in patient-reported gastrointestinal symptom burden, using
gastrointestinal symptom rating scale (GSRS) total and subscales scores, in patients treated with SBR759 compared to patients treated with sevelamer HCl. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Assessments subjects to an additional informed consent form but included in the main protocol:
- phosphate dynamics during dialysis (evaluation of phosphate levels removed during dialysis in all patients and validation of Gutzwiller formula in 12 patients)
- Imaging and Pulse Wave Velocity procedure (evaluation of changes in bone metabolism and vascular calcification in 50 patients) |
|
| E.3 | Principal inclusion criteria |
- Men or women of at least 18 years old.
- Patient must be on maintenance renal replacement therapy (i.e. hemodialysis, hemofiltration or hemodiafiltration) 3 times per week for > 3 months before screening with a stable dialysis prescription, as defined by no change in material (i.e. dialyzer, filter/membrane) type and dialysis duration for ≥ 4 weeks before screening and planned to be maintained the same throughout the study duration.
- Patient must be on restricted phosphate diet at screening and throughout the study.
- If currently under phosphate binder therapy, patient has a controlled serum phosphate > 3.0 mg/dL (> 0.97 mmol/L) and ≤6.5 mg/dL ( ≤2.1 mmol/L) as indicated
by the single value obtained from the central laboratory at screening (i.e. obtained at a 72-hr postdialysis interval)
- Patient has a serum phosphate level ≥6.0 mg/dL ( ≥1.9 mmol/L) obtained at a
72-hr post-dialysis interval, from central laboratory, prior to randomization and study
treatment initiation (i.e. after 2 weeks washout if no exception is applicable
- Patient must have a Urea Reduction Ratio of ≥ 60% (obtained from central laboratory at screening).
- Patient must be on a stable phosphate binder dose (i.e. No change in prescribed dose) or not have received phosphate binder therapy for at least 4 weeks prior to
screening.
- Patient must, in the investigator’s opinion, be compliant with prescribed phosphate
binders.
- If patient is currently being treated with calcimimetics, the prescribed dose must be
constant for at least 30 days prior to baseline and should remain constant during the total core study duration.
- If patient is currently being treated with vitamin D, the prescribed dose must be constant for at least 30 days prior to screening and should remain constant during the total core study duration.
|
|
| E.4 | Principal exclusion criteria |
Patient is on peritoneal dialysis.
Patient has a parathyroidectomy within 3 months prior to screening or transplant scheduled during the study.
Patient has an uncontrolled hyperparathyroidism (i.e. intact PTH > 800pg/ml obtained from the central laboratory at screening).
Patient has a history of hemochromatosis or ferritin > 1000 μg/L obtained from the central laboratory at screening.
Patient has a clinically significant GI disorder
Patient has a chronic unstable GI disorder
Patient has an history of major gastrointestinal tract surgery
- Patient has a clinically significant unstable medical condition as per investigator judgement.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
- Patient is known to currently have a drug or alcohol abuse problem.
- Patient has a known history of immunodeficiency disease, e.g. existing positive HIV
(ELISA or Western blot) test result.
- History of intolerance to sevelamer HCl.
- Patient is currently being treated with oral iron.
- Patient currently has an active antiviral treatment for Hepatitis B and/or C (within 30 days prior to screening).
- Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives of enrollment, whichever is longer
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical
classes
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant. UNLESS they are using a highly effective method of birth control
(i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some
intrauterine devices (IUDs).
- Patient is treated with osteoporosis treatment within 30 days prior to screening
- Patient has a transferrin saturation > 60%, obtained from central lab, at screening |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Number of patients with a serum phosphate level below or equal to 5.5 mg/dL (1.78 mmol/L) |
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| change in bone metabolism and vascular calcification biomarkers; dynamics of phosphate levels in HD |
|
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Stratified per serum phosphorus levels (<or>= to 75.mg/dL) |
|
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| 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 | 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
|
| The trial will be considered completed after completion of the extension study, including the 2 weeks random treatment withdrawal period. |
|
| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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