Phase3b study of TRC101 in Delaying Chronic Kidney Disease Progression
Research type
Research Study
Full title
A Phase 3b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of TRC101 in Delaying Chronic Kidney Disease Progression in Subjects with Metabolic Acidosis
IRAS ID
251419
Contact name
Mohsen El Kossi
Contact email
Sponsor organisation
Tricida Inc.
Eudract number
2018-001303-36
Clinicaltrials.gov Identifier
125,832, IND Number
Duration of Study in the UK
3 years, 10 months, 30 days
Research summary
Summary of Research
Chronic kidney disease occurs when the kidneys are damaged. Over time this causes the kidneys to function less well and they become unable to clean the body by eliminating waste products. Some of the waste products that build up in the body cause the blood to become acidic (“metabolic acidosis”). When there is too much acid in the blood, the blood bicarbonate level goes down, below the normal range. Increasing the blood bicarbonate level makes the level of acid in the blood go down. When left untreated, metabolic acidosis may speed up worsening of kidney disease, lead to muscle weakening and result in thinner bones. When kidney disease becomes very advanced, dialysis or a kidney transplant is needed for survival.
This research study is being done to learn whether TRC101 (the study medication) can slow down the worsening of kidney disease. TRC101 is an” investigational” medication, which means that it is still being tested for safety and effectiveness. TRC101 works by removing acid from the stomach and intestines. This causes the blood acid level to go down and the blood bicarbonate level to go up. By raising the blood bicarbonate, TRC101 may help to slow down the worsening of kidney disease.
This research study will enrol both male and female participants, 18 to 85 years of age who have kidney disease and a lower than normal level of bicarbonate in their blood. The research study will consist of an optional pre-screening period, screening period, Part A, Part B and a post-treatment follow-up period. The treatment period in part A will last for 4 to 8 weeks and in Part B for an average of 3.5 years. Some participants will complete their participation at the end of Part A.
Summary of Results
The VALOR-CKD trial did not meet its primary endpoint, which was defined as the time to the first occurrence of any event in the composite endpoint of renal death, end-stage renal disease (ESRD), or a confirmed greater than or equal to 40% reduction in estimated glomerular filtration rate (eGFR), also known as DD40. One hundred forty-nine veverimer-treated patients versus 148 placebo-treated patients experienced a DD40 primary endpoint event, representing a veverimer to placebo hazard ratio of 0.99 [95% CI, 0.78, 1.24; (p=0.898)] over the 26.7 months median duration of treatment. Given the failure on the primary endpoint, the prespecified hierarchical analysis did not permit statistical testing of the secondary endpoints, however, the nominal p-values for all of these endpoints were non-significant. The overall safety profile of veverimer observed in both Part A and Part B of the trial was consistent with that expected for the general population of patients with Stage 3 to 5 chronic kidney disease (CKD). The incidence of all-cause death (14.2% vs. 14.0%) and cardiovascular death (5.7% vs. 6.0%) was balanced between patients randomized to veverimer and placebo. The percentage of patients reporting serious adverse events (SAEs) (26.7% and 27.8%) was also similar in the two respective groups. There were only 2 treatment-related SAEs. Adverse events resulting in discontinuation of randomized study drug treatment were reported for 6.6% of the veverimer group and 6.0% of the placebo group. The majority of adverse events were mild to moderate in severity and balanced between the two groups. The most common adverse events (i.e., those reported in at least 5% of the veverimer group), in the veverimer and placebo groups, respectively, were hypertension (8.8% vs. 9.6%), hyperkalemia (7.4% vs. 5.8%), COVID-19 (5.3% vs. 7.3%), headache (5.3% vs. 5.0%), and anemia (5.1% vs. 4.9%).
REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
18/EM/0298
Date of REC Opinion
13 Nov 2018
REC opinion
Further Information Favourable Opinion