Evaluation of Effect of TRC101 on Progression of Chronic Kidney Disease in Subjects With Metabolic Acidosis

Chronic Kidney Disease Clinical Trial

— VALOR-CKD  

Official 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03710291
• Other study ID #: TRCA-303
• Secondary ID: 2018-001303-36
• Status: Terminated
• Phase: Phase 3
• Start date: November 20, 2018
• Est. completion date: September 27, 2022

Study information

• Verified date: October 2022
• Source: Tricida, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effect of TRC101 on the progression of chronic kidney disease (CKD) and to evaluate the safety profile of TRC101 in CKD patients with metabolic acidosis.

Description:

This is a randomized, double-blind, placebo-controlled trial. Eligible subjects will be randomized in a 1:1 ratio to TRC101 or placebo. The primary endpoint of the study will be progression of renal disease, defined by time to first occurrence of any event in the composite endpoint consisting of a confirmed ≥ 40% reduction in eGFR, end-stage renal disease (ESRD), and renal death. The study will terminate when the independent blinded Clinical Endpoint Adjudication Committee has positively adjudicated the targeted number of primary efficacy endpoint events. The maximum duration of follow-up for a randomized subject is anticipated to be approximately 6 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1480
• Est. completion date: September 27, 2022
• Est. primary completion date: August 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Estimated glomerular filtration rate (eGFR) 20 - 40 mL/min/1.73m^2.
• Serum bicarbonate 12 - 20 mEq/L.
• On maximum tolerated dose of ACE inhibitor and/or ARB.

Exclusion Criteria:

• Acute metabolic acidosis.
• Anticipated dialysis or kidney transplant within 6 months.
• Recent acute kidney injury.

Related Conditions & MeSH terms

• Acidosis
• Chronic Kidney Disease
• Kidney Diseases
• Metabolic Acidosis
• Renal Insufficiency, Chronic

Intervention

Drug:
• TRC101
Oral, non-absorbed, polymeric hydrochloric acid binder
• Placebo
Placebo comparator

Locations

Country	Name	City	State
Albania	Investigative Site 1103	Shkodër
Albania	Investigative Site 1101	Tirana
Argentina	Investigative Site 4402	Buenos Aires
Argentina	Investigative Site 4408	Córdoba
Argentina	Investigative Site 4414	Córdoba
Argentina	Investigative Site 4410	Corrientes
Argentina	Investigative Site 4405	Mar Del Plata
Argentina	Investigative Site 4409	San Luis
Armenia	Investigative site 2801	Yerevan
Armenia	Investigative Site 2802	Yerevan
Armenia	Investigative Site 2803	Yerevan
Armenia	Investigative Site 2805	Yerevan
Armenia	Investigative Site 2807	Yerevan
Armenia	Investigative Site 2809	Yerevan
Australia	Investigative Site 5101	Gosford
Belarus	Investigative Site 1502	Grodno
Belgium	Investigative Site 3103	Liège
Belgium	Investigative Site 3108	Liège
Brazil	Investigative Site 4518	Caxias Do Sul
Brazil	Investigative Site 4504	Curitiba
Brazil	Investigative Site 4516	Curitiba
Brazil	Investigative Site 4507	Juiz De Fora
Brazil	Investigative Site 4506	São Paulo
Brazil	Investigative Site 4508	São Paulo
Brazil	Investigative Site 4509	São Paulo
Brazil	Investigative Site 4517	São Paulo
Brazil	Investigative Site 4519	São Paulo
Bulgaria	Investigative Site 1211	Kozloduy
Bulgaria	Investigative Site 1213	Montana
Bulgaria	Investigative Site 1210	Pleven
Bulgaria	Investigative Site 1205	Ruse
Bulgaria	Investigative Site 1212	Ruse
Bulgaria	Investigative Site 1206	Sevlievo
Bulgaria	Investigative Site 1204	Sliven
Bulgaria	Investigative Site 1201	Sofia
Bulgaria	Investigative Site 1208	Veliko Tarnovo
Bulgaria	Investigative Site 1203	Yambol
Canada	Investigative Site 4203	Brampton
Canada	Investigative Site 4202	Kitchener
Canada	Investigative Site 4201	London
Canada	Investigative Site 4204	Québec
Canada	Investigative Site 4208	Winnipeg
Chile	Investigative Site 4604	Concepción
Chile	Investigative Site 4601	Providencia
Chile	Investigative Site 4602	Temuco
Colombia	Investigative Site 4703	Barranquilla
Colombia	Investigative Site 4708	Barranquilla
Colombia	Investigative Site 4712	Barranquilla
Colombia	Investigative Site 4705	Cali
Colombia	Investigative Site 4709	Zipaquirá
Czechia	Investigative Site 2106	Sokolov
Czechia	Investigative Site 2107	Znojmo
France	Investigative Site 3209	Boulogne-Billancourt
France	Investigative Site 3205	Lille
Georgia	Investigative Site 2201	Batumi
Georgia	Investigative Site 2202	Kutaisi
Georgia	Investigative Site 2204	Tbilisi
Georgia	Investigative Site 2205	Tbilisi
Georgia	Investigative Site 2206	Tbilisi
Georgia	Investigative Site 2207	Tbilisi
Georgia	Investigative Site 2208	Tbilisi
Georgia	Investigative Site 2209	Tbilisi
Georgia	Investigative Site 2210	Tbilisi
Georgia	Investigative Site 2211	Tbilisi
Georgia	Investigative Site 2212	Tbilisi
Georgia	Investigative Site 2213	Tbilisi
Georgia	Investigative Site 2214	Tbilisi
Hong Kong	Investigative Site 6101	Hong Kong
Hong Kong	Investigative Site 6103	Hong Kong
Hong Kong	Investigative Site 6105	Hong Kong
Hong Kong	Investigative Site 6104	Sha Tin
Hungary	Investigative Site 2311	Baja
Hungary	Investigative Site 2304	Budapest
Hungary	Investigative Site 2312	Budapest
Hungary	Investigative Site 2306	Gyor
Hungary	Investigative Site 2309	Kaposvár
Hungary	Investigative Site 2310	Kistarcsa
Hungary	Investigative Site 2316	Nagykanizsa
Israel	Investigative Site 3913	Afula
Israel	Investigative Site 3902	Ashkelon
Israel	Investigative Site 3905	Jerusalem
Israel	Investigative Site 3911	Tel Aviv
Israel	Investigative Site 3903	Tiberias
Italy	Investigative Site 3408	Genova
Italy	Investigative Site 3407	Messina
Italy	Investigative Site 3405	Milano
Italy	Investigative Site 3406	Napoli
Italy	Investigative Site 3402	Pavia
Italy	Investigative Site 3409	Reggio Calabria
Korea, Republic of	Investigative Site 5207	Ansan
Korea, Republic of	Investigative Site 5203	Anyang
Korea, Republic of	Investigative Site 5218	Cheonan
Korea, Republic of	Investigative Site 5204	Daejeon
Korea, Republic of	Investigative Site 5205	Goyang
Korea, Republic of	Investigative Site 5215	Guri-si
Korea, Republic of	Investigative Site 5208	Seoul
Korea, Republic of	Investigative Site 5213	Seoul
Korea, Republic of	Investigative Site 5212	Wonju
Malaysia	Investigative Site 6208	Klang
Malaysia	Investigative Site 6203	Kota Bharu
Malaysia	Investigative Site 6207	Kota Bharu
Malaysia	Investigative Site 6202	Kuala Lumpur
Malaysia	Investigative Site 6204	Kuantan
Malaysia	Investigative Site 6205	Kulim
Malaysia	Investigative Site 6210	Pulau Pinang
Malaysia	Investigative Site 6206	Seri Manjung
Malaysia	Investigative Site 6201	Sungai Petani
Mexico	Investigative Site 4307	Cuernavaca
Mexico	Investigative Site 4304	Guadalajara
Mexico	Investigative Site 4313	Guadalajara
Mexico	Investigative Site 4319	Guadalajara
Mexico	Investigative Site 4301	Mérida
Mexico	Investigative Site 4316	Mérida
Mexico	Investigative Site 4302	Mexico City
Mexico	Investigative Site 4311	Mexico City
Mexico	Investigative Site 4325	Mexico City
Mexico	Investigative Site 4320	Monterrey
Mexico	Investigative Site 4315	Morelia
Mexico	Investigative Site 4324	Morelia
Mexico	Investigative Site 4310	Veracruz
Mexico	Investigative Site 4305	Xalapa
Mexico	Investigative Site 4312	Zapopan
Netherlands	Investigative Site 3507	Alkmaar
Netherlands	Investigative Site 3505	Amersfoort
Netherlands	Investigative Site 3503	Groningen
North Macedonia	Investigative Site 1304	Bitola
North Macedonia	Investigative Site 1305	Shtip
North Macedonia	Investigative Site 1301	Skopje
North Macedonia	Investigative Site 1303	Skopje
North Macedonia	Investigative Site 1302	Struga
Poland	Investigative Site 2421	Kraków
Poland	Investigative Site 2414	Warsaw
Poland	Investigative Site 2412	Zabrze
Portugal	Investigative Site 3604	Aveiro
Portugal	Investigative Site 3603	Lisboa
Portugal	Investigative Site 3607	Lisboa
Portugal	Investigative Site 3605	Vila Nova De Gaia
Romania	Investigative Site 1412	Oradea
Serbia	Investigative Site 2501	Belgrade
Serbia	Investigative Site 2508	Kragujevac
Serbia	Investigative Site 2510	Krusevac
Serbia	Investigative Site 2505	Niš
Serbia	Investigative Site 2514	Užice
Serbia	Investigative Site 2503	Vršac
Serbia	Investigative Site 2511	Zajecar
Singapore	Investigative Site 6401	Singapore
Singapore	Investigative Site 6403	Singapore
Singapore	Investigative Site 6404	Singapore
Slovakia	Investigative Site 2604	Košice
Slovakia	Investigative Site 2606	Košice
Slovakia	Investigative Site 2603	Svidník
Spain	Investigative Site 3706	Barcelona
Spain	Investigative Site 3707	Barcelona
Spain	Investigative Site 3716	Barcelona
Taiwan	Investigative Site 6512	Changhua
Taiwan	Investigative Site 6502	Hualien City
Taiwan	Investigative Site 6501	Kaohsiung
Taiwan	Investigative Site 6504	New Taipei City
Taiwan	Investigative Site 6506	Taichung
Taiwan	Investigative Site 6507	Taichung
Taiwan	Investigative Site 6510	Taichung
Taiwan	Investigative Site 6503	Tainan
Taiwan	Investigative Site 6509	Taipei
Taiwan	Investigative Site 6511	Taipei
Ukraine	Investigative Site 2712	Dnipro
Ukraine	Investigative Site 2714	Ivano-Frankivs'k
Ukraine	Investigative Site 2704	Kharkiv
Ukraine	Investigative Site 2707	Kharkiv
Ukraine	Investigative Site 2713	Kharkiv
Ukraine	Investigative Site 2717	Kharkiv
Ukraine	Investigative Site 2721	Kharkiv
Ukraine	Investigative Site 2703	Kyiv
Ukraine	Investigative Site 2705	Kyiv
Ukraine	Investigative Site 2706	Kyiv
Ukraine	Investigative Site 2709	Kyiv
Ukraine	Investigative Site 2710	Kyiv
Ukraine	Investigative Site 2716	Kyiv
Ukraine	Investigative Site 2718	Ternopil'
Ukraine	Investigative Site 2719	Zaporizhzhya
Ukraine	Investigative Site 2715	Zhytomyr
United Kingdom	Investigative Site 3815	Coventry
United Kingdom	Investigative Site 3804	Nottingham
United Kingdom	Investigative Site 3801	Swansea
United States	Investigative Site 4127	Augusta	Georgia
United States	Investigative Site 4136	Azusa	California
United States	Investigative Site 4124	Bethlehem	Pennsylvania
United States	Investigative Site 4157	Boca Raton	Florida
United States	Investigative Site 4146	Bradenton	Florida
United States	Investigative Site 4102	Coral Springs	Florida
United States	Investigative Site 4148	Denver	Colorado
United States	Investigative Site 4153	Fort Lauderdale	Florida
United States	Investigative Site 4141	Greenbelt	Maryland
United States	Investigative Site 4108	Greenville	North Carolina
United States	Investigative Site 4122	Hollywood	Florida
United States	Investigative Site 4123	Hollywood	Florida
United States	Investigative Site 4155	Kansas City	Missouri
United States	Investigative Site 4106	Kinston	North Carolina
United States	Investigative Site 4104	Miami	Florida
United States	Investigative Site 4130	Miami Lakes	Florida
United States	Investigative Site 4132	Nashville	Tennessee
United States	Investigative Site 4107	New Bern	North Carolina
United States	Investigative Site 4116	Port Charlotte	Florida
United States	Investigative Site 4152	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Tricida, Inc.

Countries where clinical trial is conducted

United States,  Albania,  Argentina,  Armenia,  Australia,  Belarus,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Czechia,  France,  Georgia,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  North Macedonia,  Poland,  Portugal,  Romania,  Serbia,  Singapore,  Slovakia,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety of TRC101	Frequency, intensity, and relationship to study drug of adverse events and serious adverse events.	Through study completion, up to approximately 6 years.
Primary	Progression of chronic kidney disease	Time to first occurrence of: a confirmed =40% reduction in eGFR; ESRD; renal death.	Through study completion, up to approximately 6 years.
Secondary	Death (all-cause), ESRD or a confirmed =50% reduction in eGFR	Time to first occurrence of: death (all-cause); ESRD; a confirmed =50% reduction in eGFR.	Through study completion, up to approximately 6 years.
Secondary	Physical functioning (subjective)	Kidney Disease Quality of Life Physical Functioning Survey.	18 months after randomization.
Secondary	Physical functioning (objective)	Repeated chair stand test.	18 months after randomization.
Secondary	ESRD or renal death	Time to ESRD or renal death.	Through study completion, up to approximately 6 years.
Secondary	Primary outcome measure OR cardiovascular death	Time to first occurrence of: a confirmed =40% reduction in eGFR; ESRD; renal death; cardiovascular death.	Through study completion, up to approximately 6 years.
Secondary	Serum creatinine	Time to first occurrence of a confirmed doubling of serum creatinine.	Through study completion, up to approximately 6 years.
Secondary	=50% reduction in eGFR	Time to first occurrence of a confirmed =50% reduction in eGFR.	Through study completion, up to approximately 6 years.
Secondary	=40% reduction in eGFR	Time to first occurrence of a confirmed =40% reduction in eGFR.	Through study completion, up to approximately 6 years.
Secondary	All-cause hospitalization	Frequency of all-cause hospitalization.	Through study completion, up to approximately 6 years.
Secondary	Cardiovascular death	Time to cardiovascular death.	Through study completion, up to approximately 6 years.
Secondary	All-cause mortality	Time to all-cause mortality.	Through study completion, up to approximately 6 years.