E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Longstanding kidney disease |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 effect of TRC101 on the progression of chronic kidney disease and to evaluate the safety profile of TRC101 in CKD patients with metabolic acidosis. |
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E.2.2 | Secondary objectives of the trial |
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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 |
DXA sub-study Dual energy x-ray absorptiometery (DXA) scans will be performed in a subset of subjects (approximately 200 to 400) to evaluate bone mineral density and trabecular bone score. These subjects will be enrolled from a subset of sites who have qualified DXA facilities if they consent to undergo the scans. |
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E.3 | Principal inclusion criteria |
1. Male or female subjects 18 to 85 years of age, inclusive. 2. The mean of two Screening eGFR measurements, drawn at least 2 weeks apart and both within 6 weeks of the first day of Part A, is 20 to 40 mL/min/1.73m2, inclusive. 3. Have stable renal function as defined by eGFR Screening values that are not different by > 20% (the higher of the two Screening eGFR values will be used as the denominator to calculate the 20% allowable difference). 4. Based on onsite measurement using an i-STAT point of care device, have three serum bicarbonate values, each ≥ 2 weeks apart from each other and all within 6 weeks of the A1 Visit, in the range from 12 to 20 mEq/L, inclusive. 5. Mean systolic and diastolic blood pressure (determined as the average of three replicates) must be < 160/92 mmHg at the Screening 2 Visit. 6. Receiving treatment with an ACE inhibitor and/or ARB at the maximum tolerated (for the individual subject) dose within the country-specific labeled dose range, without adjustments, for ≥ 4 weeks prior to the Screening 1 Visit and during the Screening Period. 7. If receiving an oral alkali supplement, the dose must be stable for ≥ 2 weeks prior to Screening 1 Visit and during the Screening Period. If not receiving alkali treatment, there must be no such treatment within the 2 weeks prior to Screening 1 Visit or during the Screening Period. 8. Have a hemoglobin A1c (HbA1c) value of ≤ 11.0% (0.11 fraction; 97 mmol/mol) at the Screening 1 Visit
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E.4 | Principal exclusion criteria |
1. Have any level of low serum bicarbonate at either Screening Visit that, in the opinion of the Investigator, requires emergency intervention or evaluation for an acute acidotic process. 2. Have had anuria, dialysis, or acute kidney injury/acute renal failure in the 3 months prior to the Screening 1 Visit. 3. Had heart failure with maximum New York Heart Association (NYHA) Class IV symptoms during the 3 months prior to the Screening 1 Visit. 4. Had a heart, liver or kidney transplant. 5. Have an ileostomy or colostomy or have had a bowel resection or bariatric surgery. Subjects who have had gastric lap band procedures (no gastric resection) are allowed. 6. Have a corrected serum calcium < 8.0 mg/dL (80 mg/L; 2 mmol/L) at the Screening 1 Visit, based on central laboratory measurement.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression of chronic kidney disease, defined by time to first occurrence of any event in the composite endpoint consisting of the following as adjudicated by the independent blinded Clinical Endpoint Adjudication Committee (CEAC): • A confirmed ≥ 40% reduction in eGFR • End-stage renal disease (ESRD) • Renal death |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The time to first occurrence of any component of the composite endpoint as adjudicated by an independent blinded CEAC. |
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E.5.2 | Secondary end point(s) |
1. Time to ESRD 2. eGFR slope 3. Change from baseline in the total score of the KDQOL Physical Functioning Survey at the end of treatment or last measurement prior to initiation of renal replacement therapy (RRT), whichever occurs first 4. Time to first occurrence of the primary composite endpoint or cardiovascular (CV) death 5. Frequency of all-cause hospitalization |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Time to occurrence of ESRD 2. At end of treatment 3. At end of treatment or last measurement prior to initiation of RRT, whichever occurs first 4. Time to first occurrence of primary composite endpoint or CV death 5. At end of treatment |
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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 | No |
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) | 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 | Yes |
E.8.1.7.1 | Other trial design description |
This study includes a single-blind period of 4-8 weeks and a double-blind period of approx 3.5 years |
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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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 158 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
Colombia |
Hong Kong |
Israel |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Singapore |
Taiwan |
United States |
France |
Poland |
Bulgaria |
Netherlands |
Romania |
Spain |
Czechia |
Germany |
Italy |
Albania |
Belgium |
Georgia |
Hungary |
North Macedonia |
Portugal |
Serbia |
Slovakia |
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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The point in time when all subjects who are required to complete and likely to complete the 2-Week Post-Treatment Visit have done so. |
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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 | 4 |
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 | 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 |