Trial Outcomes & Findings for Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD (NCT NCT03203642)

NCT ID: NCT03203642

Last Updated: 2023-02-06

Results Overview

htTKV was calculated using total kidney volume (in milliliters) obtained from magnetic resonance imaging (MRI) divided by height (in meters). Least square (LS) mean and standard error (SE) were estimated by using analysis of covariance (ANCOVA) model. Change from Baseline in htTKV at Month 12 was reported in this outcome measure.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

Baseline (Day 1), Month 12

Results posted on

2023-02-06

Participant Flow

The study was conducted at 20 active sites in the United States. A total of 191 participants were screened between 12 October 2017 and 29 January 2020, of which 80 participants were enrolled.

Participants were randomized in a 1:1 ratio to receive tesevatinib or placebo.

Participant milestones

Participant milestones
Measure	Tesevatinib Participants received tesevatinib 50 milligrams (mg) tablet orally once daily (QD) for up to 25.3 months.	Placebo Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.
Overall Study STARTED	40	40
Overall Study Treated	38	40
Overall Study COMPLETED	25	29
Overall Study NOT COMPLETED	15	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Tesevatinib Participants received tesevatinib 50 milligrams (mg) tablet orally once daily (QD) for up to 25.3 months.	Placebo Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.
Overall Study Adverse Event	3	1
Overall Study Withdrawal by Subject	6	6
Overall Study Lost to Follow-up	2	1
Overall Study Termination of the study by sponsor	1	1
Overall Study Participant moved	0	1
Overall Study Investigator's decision	3	0
Overall Study Other than above specified	0	1

Baseline Characteristics

Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tesevatinib n=38 Participants Participants received tesevatinib 50 mg tablet orally once daily (QD) for up to 25.3 months.	Placebo n=40 Participants Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.	Total n=78 Participants Total of all reporting groups
Age, Continuous	47.0 years STANDARD_DEVIATION 9.6 • n=5 Participants	45.6 years STANDARD_DEVIATION 10.0 • n=7 Participants	46.3 years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	18 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	22 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants	33 Participants n=7 Participants	65 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Month 12

Population: Analysis was performed on efficacy population which included all randomized participants who received at least 1 dose of study drug and completed at least 12 months of tesevatinib or placebo treatment and had a centrally read MRI at Baseline and after 12 months of treatment.

Outcome measures

Outcome measures
Measure	Tesevatinib n=31 Participants Participants received tesevatinib 50 mg tablet orally QD for up to 25.3 months.	Placebo n=34 Participants Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.
Change From Baseline in Height Adjusted Total Kidney Volume (htTKV) at Month 12	0.0236 milliliters per meter Standard Error 0.0059	0.0288 milliliters per meter Standard Error 0.0057

PRIMARY outcome

Timeframe: Baseline (Day 1), Month 18

Population: Analysis was performed on efficacy population.

htTKV was calculated using total kidney volume (in milliliters) obtained from MRI divided by height (in meters). LS mean and SE were estimated by using ANCOVA model. Change from Baseline in htTKV at Month 18 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Tesevatinib n=31 Participants Participants received tesevatinib 50 mg tablet orally QD for up to 25.3 months.	Placebo n=34 Participants Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.
Change From Baseline in Height Adjusted Total Kidney Volume at Month 18	0.0383 milliliters per meter Standard Error 0.0081	0.0425 milliliters per meter Standard Error 0.0075

PRIMARY outcome

Timeframe: Baseline (Day 1), Month 24

Population: Analysis was performed on efficacy population.

Outcome measures

Outcome measures
Measure	Tesevatinib n=31 Participants Participants received tesevatinib 50 mg tablet orally QD for up to 25.3 months.	Placebo n=34 Participants Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.
Change From Baseline in Height Adjusted Total Kidney Volume at Month 24	0.0485 milliliters per meter Standard Error 0.0103	0.0607 milliliters per meter Standard Error 0.0095

PRIMARY outcome

Timeframe: Baseline (Day 1), End of study (anytime up to 26 months)

Population: Analysis was performed on efficacy population.

Outcome measures

Outcome measures
Measure	Tesevatinib n=31 Participants Participants received tesevatinib 50 mg tablet orally QD for up to 25.3 months.	Placebo n=34 Participants Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.
Change From Baseline in Height Adjusted Total Kidney Volume at End of Study	0.0604 milliliters per meter Standard Error 0.0090	0.0589 milliliters per meter Standard Error 0.0094

SECONDARY outcome

Timeframe: From Baseline (Day 1) up to 30 days post last dose of study drug (i.e., up to 26 months)

Population: Analysis was performed on safety population which included all participants who received at least 1 dose of study drug and were analyzed according to the study drug they actually received.

An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. TEAEs were AEs that developed or worsened or became serious from the first dose (Day 1) of the study drug until end of study.

Outcome measures

Outcome measures
Measure	Tesevatinib n=38 Participants Participants received tesevatinib 50 mg tablet orally QD for up to 25.3 months.	Placebo n=40 Participants Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	37 Participants	40 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Months 12, 18, 24 and at end of study (i.e., anytime up to 26 months)

Population: Analysis was performed on efficacy population.

eGFR is a test for renal function. eGFR was calculated by using the 4-variable modification of diet in renal disease (MDRD-4) formula reported as milliliters per minute per 1.73 square meter (mL/min/1.73 m\^2). LS mean and SE were estimated using ANCOVA model.

Outcome measures

Outcome measures
Measure	Tesevatinib n=31 Participants Participants received tesevatinib 50 mg tablet orally QD for up to 25.3 months.	Placebo n=34 Participants Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 18, 24 and End of Study Month 12	-6.8032 mL/min/1.73m^2 Standard Error 1.2293	-2.1780 mL/min/1.73m^2 Standard Error 1.1709
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 18, 24 and End of Study Month 18	-7.3626 mL/min/1.73m^2 Standard Error 1.6645	-3.8950 mL/min/1.73m^2 Standard Error 1.6971
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 18, 24 and End of Study Month 24	-9.7307 mL/min/1.73m^2 Standard Error 1.4708	-6.4070 mL/min/1.73m^2 Standard Error 1.4138
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 18, 24 and End of Study End of study	-3.2757 mL/min/1.73m^2 Standard Error 0.5990	-3.7497 mL/min/1.73m^2 Standard Error 0.6323

Adverse Events

Tesevatinib

Serious events: 6 serious events

Other events: 37 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tesevatinib n=38 participants at risk Participants received tesevatinib 50 mg tablet orally QD for up to 25.3 months.	Placebo n=40 participants at risk Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.
Infections and infestations Appendicitis	0.00% 0/38 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.	2.5% 1/40 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.
Infections and infestations Renal cyst infection	2.6% 1/38 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.	0.00% 0/40 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Pain in extremity	2.6% 1/38 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.	0.00% 0/40 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	2.6% 1/38 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.	0.00% 0/40 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.
Cardiac disorders Coronary artery disease	2.6% 1/38 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.	0.00% 0/40 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.
Eye disorders Retinal detachment	2.6% 1/38 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.	0.00% 0/40 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.
Gastrointestinal disorders Colitis ulcerative	2.6% 1/38 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.	0.00% 0/40 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.
Metabolism and nutrition disorders Dehydration	2.6% 1/38 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.	0.00% 0/40 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/38 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.	2.5% 1/40 • From Baseline (Day 1) up to 30 days post last dose of the study drug (i.e., up to 26 months) Reported AEs were TEAEs that developed or worsened or became serious from the first dose (Day 1) of the study drug up to end of the study. Analysis was performed on safety population.

Other adverse events

Additional Information

Trial Transparency Team

Kadmon, a Sanofi Company

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

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