Trial Outcomes & Findings for Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS) (NCT NCT03493685)

Last Updated: 2025-06-12

Results Overview

The total eGFR slope over 2 years, defined as the slope of eGFR following initiation of randomized treatment (ie, Day 1 to Week 108). Estimates are calculated from a mixed-effects model with treatment, Baseline eGFR, analysis visit, treatment-by-analysis visit, randomization stratification factors as fixed effects, and intercept and slope for each participant as a random effect.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

371 participants

Primary outcome timeframe

From Day 1 to Week 108

Results posted on

2025-06-12

Participant Flow

The DUPLEX study is a 112-week, Phase 3, randomized, multicenter, double-blind (DB), parallel, active-control study that evaluated the safety, tolerability, and long-term nephroprotective potential of treatment with sparsentan as compared to irbesartan in participants with focal segmental glomerulosclerosis (FSGS).

The study included participants 8 to 75 years of age from the United States (US) and United Kingdom (UK), and participants 18 to 75 years of age from countries other than the US and UK. The results presented are based on the primary analysis.

Participant milestones

Participant milestones
Measure	Sparsentan Participants were randomized to receive initial dose of sparsentan as 400 milligrams (mg) over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kilograms (kg) at screening; these participants received one-half of the specified dose of sparsentan. The dose was then titrated to achieve the maximum daily target dose of 800 mg.	Irbesartan Participants were randomized to receive active control doses of irbesartan 150 mg over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kg at screening; these participants received one-half of the specified dose of irbesartan. The dose was then titrated to achieve the maximum daily target dose of 300 mg.
Overall Study STARTED	184	187
Overall Study COMPLETED	168	171
Overall Study NOT COMPLETED	16	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Sparsentan Participants were randomized to receive initial dose of sparsentan as 400 milligrams (mg) over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kilograms (kg) at screening; these participants received one-half of the specified dose of sparsentan. The dose was then titrated to achieve the maximum daily target dose of 800 mg.	Irbesartan Participants were randomized to receive active control doses of irbesartan 150 mg over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kg at screening; these participants received one-half of the specified dose of irbesartan. The dose was then titrated to achieve the maximum daily target dose of 300 mg.
Overall Study Death	4	3
Overall Study Lost to Follow-up	3	2
Overall Study Physician Decision	2	0
Overall Study Withdrawal by Subject	7	11

Baseline Characteristics

Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sparsentan n=184 Participants Participants were randomized to receive initial dose of Sparsentan as 400 milligrams (mg) over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kilograms (kg) at screening; these participants received one-half of the specified dose of Sparsentan. The dose was then titrated to achieve the maximum daily target dose of 800 mg.	Irbesartan n=187 Participants Participants were randomized to receive active control doses of Irbesartan 150 mg over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kg at screening; these participants received one-half of the specified dose of Irbesartan. The dose was then titrated to achieve the maximum daily target dose of 300 mg.	Total n=371 Participants Total of all reporting groups
Age, Continuous	41.7 Years STANDARD_DEVIATION 16.53 • n=5 Participants	41.5 Years STANDARD_DEVIATION 17.25 • n=7 Participants	41.6 Years STANDARD_DEVIATION 16.87 • n=5 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	88 Participants n=7 Participants	171 Participants n=5 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	99 Participants n=7 Participants	200 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	34 Participants n=5 Participants	44 Participants n=7 Participants	78 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	147 Participants n=5 Participants	135 Participants n=7 Participants	282 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	23 Participants n=5 Participants	27 Participants n=7 Participants	50 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	16 Participants n=5 Participants	9 Participants n=7 Participants	25 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	134 Participants n=5 Participants	135 Participants n=7 Participants	269 Participants n=5 Participants
Race/Ethnicity, Customized Other	5 Participants n=5 Participants	12 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 to Week 108

Population: Full Analysis Set.

Outcome measures

Outcome measures
Measure	Sparsentan n=184 Participants Participants were randomized to receive initial dose of Sparsentan as 400 milligrams (mg) over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kilograms (kg) at screening; these participants received one-half of the specified dose of Sparsentan. The dose was then titrated to achieve the maximum daily target dose of 800 mg.	Irbesartan n=187 Participants Participants were randomized to receive active control doses of Irbesartan 150 mg over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kg at screening; these participants received one-half of the specified dose of Irbesartan. The dose was then titrated to achieve the maximum daily target dose of 300 mg.
Slope of Estimated Glomerular Filtration Rate (eGFR)	-5.4 milliliters/minute/1.73square meter/year Interval -6.89 to -3.93	-5.7 milliliters/minute/1.73square meter/year Interval -7.2 to -4.29

PRIMARY outcome

Timeframe: Week 36

Population: Full Analysis Set.

Percentage of participants achieving FPRE, defined as urine protein-to-creatinine ratio (UP/C) ≤1.5 grams/gram (g/g) (170 milligrams per millimoles \[mg/mmol\]) and a \>40% reduction from Baseline was analyzed using a generalized linear model to model probability of achieving FPRE. Missing responses were imputed prior to analysis using multiple imputation. A generalized linear model with appropriate link function was implemented with Baseline log (UP/C), treatment, analysis visit, treatment by analysis visit interaction, and randomization strata as fixed effects. For estimates of probability of achieving FPRE, risk difference, and odds ratio, binomial distribution with logit link was used. For relative risk, Poisson distribution with log link was used. Using Rubin's approach, estimated treatment effects are combined across all imputations to obtain overall estimates for probabilities.

Outcome measures

Outcome measures
Measure	Sparsentan n=184 Participants Participants were randomized to receive initial dose of Sparsentan as 400 milligrams (mg) over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kilograms (kg) at screening; these participants received one-half of the specified dose of Sparsentan. The dose was then titrated to achieve the maximum daily target dose of 800 mg.	Irbesartan n=187 Participants Participants were randomized to receive active control doses of Irbesartan 150 mg over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kg at screening; these participants received one-half of the specified dose of Irbesartan. The dose was then titrated to achieve the maximum daily target dose of 300 mg.
Percentage of Participants Achieving FSGS Partial Remission Endpoint (FPRE)	42.0 Percentage of participants	26.0 Percentage of participants

SECONDARY outcome

Timeframe: From Week 6 to Week 108

Population: Full Analysis Set.

The chronic eGFR slope over 2 years, defined as the slope of eGFR following the initial acute effect of randomized treatment (ie, Week 6 to Week 108). Estimates were calculated from a mixed-effects model with linear spline (ie, change point at Week 6), which included treatment, Baseline eGFR, time from Baseline (TFB) (weeks), time from change point (TFCP) (weeks), treatment-by-TFB and treatment-by-TFCP interactions, and randomization stratification factors as fixed effects, intercept and slopes as random effects. The slope difference was tested by the null hypothesis that the sum of the treatment-by-TFB and treatment-by-TFCP interactions = 0.

Outcome measures

Outcome measures
Measure	Sparsentan n=184 Participants Participants were randomized to receive initial dose of Sparsentan as 400 milligrams (mg) over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kilograms (kg) at screening; these participants received one-half of the specified dose of Sparsentan. The dose was then titrated to achieve the maximum daily target dose of 800 mg.	Irbesartan n=187 Participants Participants were randomized to receive active control doses of Irbesartan 150 mg over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kg at screening; these participants received one-half of the specified dose of Irbesartan. The dose was then titrated to achieve the maximum daily target dose of 300 mg.
Slope of eGFR Following the Initial Acute Effect of Randomized Treatment	-4.8 milliliters/minute/1.73square meter/year Interval -6.34 to -3.27	-5.7 milliliters/minute/1.73square meter/year Interval -7.2 to -4.18

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 112

Population: Full Analysis Set (Patients who Completed Blinded Treatment). Only those participants with data available at specified time points have been presented.

The change from Baseline to 4 weeks post-cessation of randomized treatment (Week 112) was analyzed via an analysis of covariance (ANCOVA) model on the natural log(eGFR) with treatment, Baseline eGFR, and randomization strata as fixed effects. Only participants who completed the 108-week treatment period were included. Estimated LS Mean and 95% CI are converted to percentages as follows: \[exponential (LS mean change from baseline in natural log(eGFR)) minus 1\] multiplied by 100. Baseline (Day 1) was defined as the last non-missing assessment prior to and including the first administration of study medication in the study including unscheduled assessments. Percent change from Baseline was calculated as "\[(Post Baseline minus Baseline value)/ Baseline value\] multiplied by 100.

Outcome measures

Outcome measures
Measure	Sparsentan n=129 Participants Participants were randomized to receive initial dose of Sparsentan as 400 milligrams (mg) over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kilograms (kg) at screening; these participants received one-half of the specified dose of Sparsentan. The dose was then titrated to achieve the maximum daily target dose of 800 mg.	Irbesartan n=136 Participants Participants were randomized to receive active control doses of Irbesartan 150 mg over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kg at screening; these participants received one-half of the specified dose of Irbesartan. The dose was then titrated to achieve the maximum daily target dose of 300 mg.
Change From Baseline in eGFR to 4 Weeks Post-cessation of Randomized Treatment	-10.4 milliliters/minute/1.73square meter Interval -12.6 to -8.13	-12.1 milliliters/minute/1.73square meter Interval -14.36 to -9.91

Adverse Events

Sparsentan

Serious events: 68 serious events

Other events: 172 other events

Deaths: 4 deaths

Irbesartan

Serious events: 82 serious events

Other events: 174 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Travere Therapeutics Call Center

Travere Therapeutics, Inc

Phone: 1-877-659-5518

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Sparsentan n=184 participants at risk Participants in this arm were randomized to receive initial dose of Sparsentan as 400 milligrams (mg) over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kilograms (kg) at screening; these participants received one-half of the specified dose of Sparsentan. The dose was then titrated to achieve the maximum daily target dose of 800 mg.	Irbesartan n=187 participants at risk Participants were randomized to receive active control doses of Irbesartan 150 mg over-encapsulated (blinded) with size 00 capsules orally once daily. A dose adjustment was made for participants whose body weight was ≤50 kg at screening; these participants received one-half of the specified dose of Irbesartan. The dose was then titrated to achieve the maximum daily target dose of 300 mg.
Infections and infestations COVID-19	22.3% 41/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	26.7% 50/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Infections and infestations Upper respiratory tract infection	5.4% 10/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	8.6% 16/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Infections and infestations Urinary tract infection	4.9% 9/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	9.1% 17/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Infections and infestations Nasopharyngitis	6.0% 11/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	4.8% 9/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Infections and infestations Influenza	3.3% 6/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	6.4% 12/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Infections and infestations Gastroenteritis	3.3% 6/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	5.3% 10/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Infections and infestations Sinusitis	4.9% 9/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	1.6% 3/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Gastrointestinal disorders Diarrhoea	13.6% 25/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	14.4% 27/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Gastrointestinal disorders Nausea	5.4% 10/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	9.6% 18/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Gastrointestinal disorders Vomiting	7.1% 13/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	4.3% 8/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Gastrointestinal disorders Abdominal pain	4.3% 8/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	5.3% 10/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Gastrointestinal disorders Abdominal pain upper	3.8% 7/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	5.9% 11/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Gastrointestinal disorders Dyspepsia	4.3% 8/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	4.8% 9/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Metabolism and nutrition disorders Hyperkalaemia	16.8% 31/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	10.7% 20/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Metabolism and nutrition disorders Gout	4.9% 9/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	3.7% 7/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
General disorders Oedema peripheral	19.6% 36/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	21.9% 41/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
General disorders Fatigue	8.7% 16/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	5.9% 11/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
General disorders Pyrexia	7.1% 13/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	4.8% 9/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Investigations Blood creatine phosphokinase increased	10.3% 19/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	4.3% 8/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Investigations Blood creatinine increased	6.5% 12/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	7.5% 14/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Investigations Glomerular filtration rate decreased	6.5% 12/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	5.9% 11/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Investigations Lipase increased	4.3% 8/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	5.9% 11/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Investigations Alanine aminotransferase increased	5.4% 10/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	2.1% 4/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Musculoskeletal and connective tissue disorders Muscle spasms	13.6% 25/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	8.0% 15/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Musculoskeletal and connective tissue disorders Back pain	8.2% 15/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	10.7% 20/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Musculoskeletal and connective tissue disorders Arthralgia	5.4% 10/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	4.3% 8/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	5.4% 10/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	2.1% 4/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Vascular disorders Hypotension	17.9% 33/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	11.2% 21/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Vascular disorders Hypertension	10.9% 20/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	12.8% 24/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Renal and urinary disorders Chronic kidney disease	7.1% 13/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	11.8% 22/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Renal and urinary disorders Acute kidney injury	4.3% 8/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	7.0% 13/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Renal and urinary disorders Nephrotic syndrome	5.4% 10/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	4.3% 8/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Renal and urinary disorders Proteinuria	3.8% 7/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	5.9% 11/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Renal and urinary disorders Renal impairment	6.0% 11/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	2.7% 5/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Nervous system disorders Dizziness	12.5% 23/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	11.2% 21/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Nervous system disorders Headache	10.9% 20/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	12.3% 23/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 13/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	8.6% 16/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.4% 10/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	1.6% 3/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Injury, poisoning and procedural complications Vaccination complication	6.5% 12/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	5.9% 11/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Blood and lymphatic system disorders Anaemia	13.0% 24/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	5.3% 10/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.
Psychiatric disorders Anxiety	2.2% 4/184 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.	4.8% 9/187 • Up to Week 112 Safety Analysis Set comprised of all participants who were randomized to receive at least 1 dose of double-blind study medication. The results presented are based on the primary analysis.