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

January 18, 2022 updated by: PTC Therapeutics

Phase 1B Study of PTC299 in Relapsed/Refractory Acute Leukemias

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
33

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80012
        • Rocky Mountain Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers, Cancer Institute of NJ
    • New York
      • New York, New York, United States, 10032
        • Columbia
      • Rochester, New York, United States, 14642
        • University of Rochester MC
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Cancer Center
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center
      • Cincinnati, Ohio, United States, 45236
        • Oncology Hematology Care, Inc.
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island, Miriam Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • SCRI Tennessee Oncology
    • Texas
      • Austin, Texas, United States, 78705
        • Texas Oncology, P.A.
      • Fort Worth, Texas, United States, 76104
        • Texas Oncology, P.A.
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78240
        • Texas Oncology, P.A. - San Antonio Medical Center
    • Washington
      • Seattle, Washington, United States, 91804
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

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.

Gastrointestinal (GI) assessments:

  • Liver malignancy (including metastases) or chronic liver disease.
  • History of Gastrointestinal surgery or procedures or conditions that might interfere with the absorption or swallowing of the study drug.

Immunologic:

  • Known hypersensitivity to study drug or its excipients.

Miscellaneous:

  • Any sign of active uncontrolled infections; any severe chronic disease potentially interfering with the protocol, including human immunodeficiency virus (HIV) infection, or active hepatitis B or C or those with a positive screen for hepatitis A Immunoglobulin M (IgM).
  • Any other malignancies within the past 2 years other than basal cell skin cancer or carcinoma in situ of the cervix.
  • Participant concomitantly receiving any other investigational agents.
  • Systemic chemotherapy within 2 weeks or investigational therapy within 5 half-lives prior to first dose of study drug, unless there is evidence of rapidly progressive disease (in which case the shorter washout of 2 weeks will be followed). For monoclonal antibodies, the washout from prior therapy will be 4 weeks, unless there is evidence of rapidly progressive disease, in which case, the shorter washout period of 2 weeks will be followed. Persistent chronic clinically significant toxicities from prior chemotherapy must not be >Grade 1. Use of hydroxyurea (Hydrea) is permitted up to 24 hours prior to start of study drug for control of proliferative disease. Hydrea treatment may be reinstated during study for control of proliferative disease, as needed, at the discretion of investigator.
  • Participants with AML that has advanced with central nervous system (CNS) involvement.
  • Participant is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
  • Participants receiving CYP2B6 substrates such as bupropion and methadone.
  • Participants receiving strong CYP3A4 inducers such as carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, and St. John's wort (hypericin) or drugs that are exclusively substrates of CYP3A4.
  • Participant is receiving moderate or strong CYP3A4 inhibitors. (Note: This exclusion criterion is not applicable to subjects participating in sub-study where only subjects who are currently on/require antifungals [prophylaxis/treatment] will be enrolled)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PTC299
PTC299 will be administered orally once daily (QD) for each 28-day cycle.
Drug: PTC299
PTC299 will be administered per the treatment arm description
Other Names:
  • Emvododstat

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number of Participants Who Discontinued Study Drug Due to Adverse Event (AE)
Time Frame: From Screening to 50 days post treatment
From Screening to 50 days post treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Time to Maximum Plasma Concentration (Tmax) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time Frame: Days 1, 15, 28, 57, 71 and 99
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
Time Frame: Days 1, 15, 28, 57, 71 and 99
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
Time Frame: Days 1, 15, 28, 57, 71 and 99
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
Time Frame: Days 1, 15, 28, 57, 71 and 99
Days 1, 15, 28, 57, 71 and 99
Estimate t1/2 of of both PTC299 and O-desmethyl PTC299 During 14-Day Washout Period
Time Frame: Day 29 through Day 42
Day 29 through Day 42
Apparent Clearance (CL/F) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time Frame: Days 1, 15, 28, 57, 71 and 99
Days 1, 15, 28, 57, 71 and 99
Apparent Volume of Distribution (Vz/F) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time Frame: Days 1, 15, 28, 57, 71 and 99
Days 1, 15, 28, 57, 71 and 99
Accumulation Ratio (R) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time Frame: Days 1, 15, 28, 57, 71 and 99
Days 1, 15, 28, 57, 71 and 99
Percentage of Participants Achieving Response Rate/Overall Response Rate Utilizing International Working Group (IWG) Response Criteria for AML
Time Frame: Up to 6 Months
Up to 6 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PTC Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 29, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 28, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 28, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 29, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 29, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 3, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 2, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 18, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PTC299-HEM-001-LEU

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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