A First in Human, Dose Escalation Study to Evaluate the Safety and Tolerability of BBP-671 in Healthy Volunteers and Patients With Propionic Acidemia or Methylmalonic Acidemia

December 20, 2023 updated by: CoA Therapeutics, Inc., a BridgeBio company

A First-in-human, Randomized, Placebo-controlled, Single and Multiple Ascending Dose Escalation to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BBP-671 in Healthy Subjects and In Patients With Propionic Acidemia or Methylmalonic Acidemia

The purpose of this study is to assess the safety, tolerability, PK and PD of BBP-671 in healthy volunteers and patients with Propionic Acidemia or Methylmalonic Acidemia.

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.

Detailed Description

This is the first-in-human study with BBP-671 and is designed to provide healthy subjects single- and multiple-dose and patient multidose safety, tolerability, PK, and PD data regarding BBP-671 for future clinical studies.

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.
79

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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Indiana
      • Topeka, Indiana, United States, 46571
        • Community Health Clinic
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • UPMC Children's Hospital of Pittsburg
    • Texas
      • Austin, Texas, United States, 78744
        • PPD Development, LP

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

15 years to 55 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria (Healthy Volunteers):

  • Subject is male or female 18 to 55 yrs old
  • Subject has a BMI 18 to 32 kg/m^2
  • Female and male subjects must use effective method of birth control
  • Female subjects must have negative pregnancy test prior to first dose of study drug
  • Subject must not have any clinically significant history or presence of ECG findings
  • Subject must be in good general health

Inclusion Criteria (PA or MMA Patients):

  • Patient is male or female 15 to 55 yrs old
  • Patient has a BMI 18 to 32 kg/m^2
  • Female and male patients must use effective method of birth control
  • Female patients must have negative pregnancy test prior to first dose of study drug
  • Patient must have confirmed PA or MMA diagnosis
  • Patient with MMA must have elevated plasma MMA levels
  • Patient is willing to provide access to medical records for the last 6-12 months of care prior to study initiation
  • Patient is on consistent disease management and treatment regimen is stable for at least 30 days prior to study initiation.

Exclusion Criteria (Healthy Volunteers):

  • Subject has used prescription drugs (contraceptive medications are allowed) within 4 weeks before first dose of study drug or over-the-counter medication within 7 days of the first dose of study drug
  • Subject who is unable or unwilling to refrain from wearing contact lenses during participation in the study.
  • Subject has a history of dry eye or eye surgery, including radial keratotomy and LASIK surgery.
  • Subject who has taken the COVID-19 vaccine, the last vaccine dose must be at least 14 days prior to first dose of study drug.
  • Subject has abnormal laboratory test results
  • Subject has a baseline eGFR <90 mL/minute
  • Subject has positive result for Hepatitis B, Hepatitis C, or HIV
  • Female subject is non-pregnant and non-lactating
  • Subject is a smoker or has used nicotine or nicotine-containing products
  • Subject has a history of alcohol or drug abuse within 12 months prior to first dose of study drug and/or has a positive result prior to dosing or throughout the study
  • Subject has donated blood or blood products >450mL within 30 days prior to study drug dosing
  • Subject has a history of relevant drug or food allergies
  • Subject has received study drug in another investigational study within 30 days of dosing
  • Subject has undergone prior liver and/ or kidney transplant.

Exclusion Criteria (PA or MMA Patients):

  • Patient has used prescription drugs (contraceptive medications are allowed) within 4 weeks before first dose of study drug or over-the-counter medication within 7 days of the first dose of study drug that is not part of their PA or MMA disease management and treatment
  • Patient who has taken the COVID-19 vaccine, the last vaccine dose (or booster) must be at least 14 days prior to first dose of study drug.
  • Patient is unable or unwilling to refrain from wearing contact lenses during participation in the study.
  • Patient has a history of dry eye or eye surgery, including radial keratotomy and LASIK surgery.
  • Patient has clinically significant abnormal laboratory test results unrelated to PA or MMA
  • Patient has a baseline eGFR <60 mL/minute
  • Patient has positive result for Hepatitis B, Hepatitis C, or HIV
  • Female patient is non-pregnant and non-lactating
  • Patient has a history of alcohol or drug abuse within 12 months prior to first dose of study drug and/or has a positive result prior to dosing or throughout the study
  • Patient has donated blood or blood products >450mL within 30 days prior to study drug dosing
  • Patient has a history of relevant drug or food allergies
  • Patient has received study drug in another investigational study within 30 days of dosing
  • PA patient has undergone prior liver and/ or kidney transplant. Prior liver and/or kidney transplant is allowed for patients with MMA.
  • Patient has had a recent infection requiring system antibiotics within 4 weeks of Baseline or any active infection that precludes the patient from participation
  • Patient has Grade 3 or 4 heart failure according to the Modified Ross Heart Failure Classification for Children or the New York Heart Association.
  • Patient has been exposed to gene therapy for PA or MMA at any time prior to study entry.
  • Patient is currently taking sensitive CYP3A4 substrates (e.g., tacrolimus or sirolimus)

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: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Triple

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: BBP-671 for SAD
The SAD portion of the study will consist of up to 8 cohorts. Six (6) healthy male or female adult subjects will be randomized to receive BBP-671 per cohort (6:2 ratio, BBP-671:placebo).
Drug: BBP-671
BBP-671, oral suspension
Drug: BBP-671
BBP-671, tablet
Placebo Comparator: Placebo for SAD
The SAD portion of the study will consist of up to 8 cohorts. Two (2) healthy male or female adult subjects will be randomized to receive matching placebo per cohort (6:2 ratio, BBP-671:placebo).
Drug: Placebo
Placebo matching BBP-671
Experimental: BBP-671 for MAD
The MAD portion of the study will consist of up to 6 cohorts. Six (6) healthy male or female adult subjects will be randomized to receive BBP-671 per cohort (6:2 ratio, BBP-671:placebo).
Drug: BBP-671
BBP-671, oral suspension
Drug: BBP-671
BBP-671, tablet
Placebo Comparator: Placebo for MAD
The MAD portion of the study will consist of up to 6 cohorts. Two (2) healthy male or female adult subjects will be randomized to receive matching placebo per cohort (6:2 ratio, BBP-671:placebo).
Drug: Placebo
Placebo matching BBP-671
Experimental: BBP-671 for SAD Food Effect
Eight (8) healthy male or female adult subjects will be randomized to receive BBP-671.
Drug: BBP-671
BBP-671, oral suspension
Drug: BBP-671
BBP-671, tablet
Experimental: BBP-671 for PA and MMA Patients
Up to sixteen (16) patients with either PA or MMA will receive BBP-671.
Drug: BBP-671
BBP-671, oral suspension
Drug: BBP-671
BBP-671, tablet

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
Measure Description
Time Frame
Incidence of adverse events following administration of BBP-671
Time Frame: 49 days
49 days
BBP-671 concentration dependent change in change from baseline in QTcF
Time Frame: 49 days
49 days
Pharmacokinetic Assessments: Cmax
Time Frame: 49 days
Time to maximum concentration (Cmax)
49 days
Pharmacokinetic Assessments: Tmax
Time Frame: 49 days
Time to reach maximum observed plasma concentration (Tmax)
49 days
Pharmacokinetic Assessments: t1/2
Time Frame: 49 days
Plasma decay half-life (t1/2)
49 days
Pharmacokinetic Assessments: AUC0-tau
Time Frame: 49 days
Area under the plasma concentration-time curve (AUC0-tau)
49 days
Pharmacokinetic Assessments: CL/F
Time Frame: 15 days
Apparent clearance (CL/F)
15 days
Pharmacokinetic Assessments: Vz/F
Time Frame: 15 days
Apparent volume of distribution (Vz/F)
15 days
Pharmacokinetic Assessments: CLr
Time Frame: 15 days
Renal clearance (CLr)
15 days

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
Measure Description
Time Frame
Food Effect: Cmax
Time Frame: 10 days
Time to maximum concentration
10 days
Food Effect: Tmax
Time Frame: 10 days
Time to reach maximum observed plasma concentration
10 days
Food Effect: AUC
Time Frame: 10 days
Area under the plasma concentration-time curve
10 days
Pharmacodynamic Assessment: Whole blood, plasma, and urine biomarker concentrations will be quantified and summarized using appropriate descriptive parameters
Time Frame: 49 days
Measurement will be done using liquid chromatography-tandem mass spectrometry
49 days

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.
CoA Therapeutics, Inc., a BridgeBio company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Medical Monitor, VP Clinical Development, CoA Therapeutics, Inc., a Bridgebio company

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.
March 25, 2021

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.
November 20, 2023

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.
November 20, 2023

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).
March 29, 2021

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.
April 5, 2021

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.
April 8, 2021

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.
December 21, 2023

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.
December 20, 2023

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.
December 1, 2023

More Information

Terms related to this study

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.
  • CoA-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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