Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias

NCT03761069 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PTC299-HEM-001-LEU
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 17

Brief Summary

This is an open-label, non-randomized, Phase 1b study to evaluate the safety, pharmacokinetics (PK) profiles, and preliminary evidence of antitumor activity of PTC299 and the metabolite, O-desmethyl PTC299, in participants with relapsed/refractory acute myeloid leukemia (AML) who have exhausted standard available therapies known to provide clinical benefit. The study is designed as a series of cohort-based dose escalations. For each cohort, a minimum of 3 evaluable participants with PK and safety data will be assessed. Additional participants will be recruited if additional PK data are needed to assess mean exposure based on the observed variability.

Conditions

Leukemia, Myeloid, Acute; AML

Keywords

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Dihydroorotate dehydrogenase (DHODH) inhibitor

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Discontinued Study Drug Due to Adverse Event (AE)

  From Screening to 50 days post treatment

Secondary Outcomes (9)

• Time to Maximum Plasma Concentration (Tmax) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

  Days 1, 15, 28, 57, 71 and 99

• Maximum Plasma Concentration (Cmax) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

  Days 1, 15, 28, 57, 71 and 99

• Area Under the Concentration-Time Curve (AUC) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

  Days 1, 15, 28, 57, 71 and 99

• Half-life (t1/2) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food

  Days 1, 15, 28, 57, 71 and 99

• Estimate t1/2 of of both PTC299 and O-desmethyl PTC299 During 14-Day Washout Period

  Day 29 through Day 42

Study Arms (1)

PTC299

EXPERIMENTAL

PTC299 will be administered orally once daily (QD) for each 28-day cycle.

Drug: PTC299

Interventions

PTC299 DRUG

PTC299 will be administered per the treatment arm description

Also known as: Emvododstat

PTC299

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must have relapsed/refractory AML and exhausted standard available therapies known to provide clinical benefit.
• Subjects must be greater than or equal to 18 years of age.
• Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (≤) 2
• Women of childbearing potential must be willing to practice a highly-effective method of birth control for up to 50 days after the last dose of study drug.
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control during the study and for up to 50 days after the last dose of study drug.
• Subjects must be willing to participate to the study, have the ability to understand and adhere to study visit schedule and other protocol procedures, and be able and willing to sign a written informed consent form.

You may not qualify if:

• Medical history:
• Women who are or plan to become pregnant, or who are currently breastfeeding.
• Persistence of any clinically relevant (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 2 or above) toxicities from previous therapy.
• Active alcohol or drug abuse.
• Previous drug-induced liver injury.
• Cardiac assessments:
• Uncontrolled congestive heart failure, unstable angina pectoris.
• History or current evidence of a myocardial infarction during the last 6 months.
• QTc prolongation greater than (\>) 500 milliseconds (msec) (Fridericia formula).
• Congenitally long QT syndrome or has received any marketed or experimental compound in the last 4 weeks or 5 half-lives (whichever is shorter) prior to entering the study with possible or known effects of QT prolongation. (If equivalent medication is not available, QTc will be closely monitored.)
• Laboratory assessments:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) greater than or equal to (≥) 1 \* upper limit of normal (ULN).
• Serum bilirubin ≥ 1 \* ULN (except those known to have Gilbert's syndrome).
• Creatinine clearance ≤45 milliliters per minute (mL/min) (estimated by Cockcroft-Gault or by 24-hour urine collection).
• Any laboratory abnormality, which in the opinion of the investigator, places the participant at an unacceptably high risk for toxicities.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (17)

Rocky Mountain Cancer Center

Aurora, Colorado, 80012, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Rutgers, Cancer Institute of NJ

New Brunswick, New Jersey, 08903, United States

Location

Columbia

New York, New York, 10032, United States

Location

University of Rochester MC

Rochester, New York, 14642, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45236, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Rhode Island, Miriam Hospital

Providence, Rhode Island, 02903, United States

Location

SCRI Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology, P.A.

Austin, Texas, 78705, United States

Location

Texas Oncology, P.A.

Fort Worth, Texas, 76104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Oncology, P.A. - San Antonio Medical Center

San Antonio, Texas, 78240, United States

Location

Swedish Cancer Institute

Seattle, Washington, 91804, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms

Interventions

emvododstat

Condition Hierarchy (Ancestors)

Leukemia; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: December 3, 2018
• Study Start: October 29, 2018
• Primary Completion: December 28, 2021
• Study Completion: December 28, 2021
• Last Updated: February 2, 2022

Record last verified: 2022-01

Locations

US (17)