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

NCT03203642 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: ACT17675KD019-211
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 19

Brief Summary

The goal of the study was to compare and evaluate safety and efficacy of tesevatinib 50 milligrams (mg) versus placebo in participants with autosomal dominant polycystic kidney disease (ADPKD).

Conditions

Autosomal Dominant Polycystic Kidney; ADPKD

Keywords

ADPKD; Autosomal Dominant Polycystic Kidney Disease; Polycystic Kidney; Tesevatinib; Polycystic Kidney Disease; PKD

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Height Adjusted Total Kidney Volume (htTKV) at Month 12

  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.

  Baseline (Day 1), Month 12

• Change From Baseline in Height Adjusted Total Kidney Volume at Month 18

  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.

  Baseline (Day 1), Month 18

• Change From Baseline in Height Adjusted Total Kidney Volume at Month 24

  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 24 was reported in this outcome measure.

  Baseline (Day 1), Month 24

• Change From Baseline in Height Adjusted Total Kidney Volume at End of Study

  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 end of study (i.e., up to 26 months) was reported in this outcome measure.

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

Secondary Outcomes (2)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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

• Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 18, 24 and End of Study

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

Study Arms (2)

Tesevatinib

EXPERIMENTAL

Participants received tesevatinib 50 mg tablet orally once daily (QD) for up to 25.3 months.

Drug: Tesevatinib

Placebo

PLACEBO COMPARATOR

Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.

Drug: Placebo

Interventions

Tesevatinib DRUG

Pharmaceutical form: Tablet; Route of administration: orally

Also known as: KD019

Tesevatinib

Placebo DRUG

Pharmaceutical form: Tablet (identical to tesevatinib); Route of administration: orally

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• ADPKD diagnosis based on Ravine's criteria.
• Cysts of at least 1 centimeter.
• Estimated glomerular filtration rate greater than or equal to (\>=) 25 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) and less than or equal to (\<=) 90 mL/min/1.73 m\^2, using the Modification of Diet in Renal Disease-4 variable formula.
• htTKV must meet the following requirements: \>= 500 milliliters (mL) for participants 18-35 years of age; \>= 750 mL for participants 36-49 years of age; \>= 900 mL for participants 50-60 years of age.
• The participant had the following laboratory values:
• Platelets greater than (\>) lower limit of normal (LLN); Hemoglobin \> 9 grams per deciliter; Total bilirubin \<= 1.5 milligrams per deciliter; Aspartate aminotransferase less than (\<) 2.5\*upper limit of normal (ULN); Alanine aminotransferase \< 2.5\*ULN; Prothrombin time/partial thromboplastin time \<=1.5\*ULN; Serum potassium levels within normal limits; Serum magnesium levels within normal limits; Albumin \>= LLN; Amylase \<=1.5\*ULN; Lipase \<=1.5\*ULN; Prothrombin time and partial thromboplastin time \<=1.5\*ULN; International normalized ratio (INR) \<=1.5, except those participants taking warfarin who must have INR \<=3.
• Female participants of childbearing potential with negative pregnancy test at screening.
• If sexually active, the participant agreed to use 2 accepted methods of contraception during the course of the study and for 6 months after their last dose of study drug.

You may not qualify if:

• Previous nephrectomy.
• Kidney transplant.
• Tuberous sclerosis.
• Hippel-Lindau disease.
• Acquired cystic disease.
• Congenital absence of 1 kidney and/or need for dialysis or transplantation in the foreseeable future.
• Moderate hematuria.
• Uncontrolled hypertension.
• Presence of renal or hepatic calculi (stones) causing symptoms.
• Received any investigational therapy within 30 days prior to initiation of therapy (Day 1 visit).
• Received tolvaptan 30 days prior to initiation of therapy (Day 1 visit).
• Received active treatment for urinary tract infection 4 weeks prior to initiation of therapy (Day 1 visit).
• History of pancreatitis or known risk of pancreatitis.
• The participant met any of the following cardiac criteria:
• Mean QTc interval corrected for heart rate using Fridericia's formula (QTcF) of \>450 milliseconds.

Sponsors & Collaborators

• Kadmon, a Sanofi Company: lead

Study Sites (19)

University of California San Diego

La Jolla, California, 92037, United States

Location

California Institute for Renal Research

La Mesa, California, 91942, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Yale Nephrology Clinical Research

New Haven, Connecticut, 06520, United States

Location

Coastal Nephrology Associates Research Center, LLC

Port Charlotte, Florida, 33952, United States

Location

Genesis Clinical Research

Tampa, Florida, 33614, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Rogosin Institute

New York, New York, 10021, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor Scott & White Research Institute

Temple, Texas, 10016, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Polycystic Kidney Diseases

Interventions

XL647

Condition Hierarchy (Ancestors)

Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Kadmon, a Sanofi Company

Contact-US@Sanofi.com

800-633-1610

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2017
• First Posted: June 29, 2017
• Study Start: October 12, 2017
• Primary Completion: January 25, 2022
• Study Completion: January 25, 2022
• Last Updated: February 6, 2023
• Results First Posted: February 6, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

US (19)