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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

Primary Purpose

Healthy Volunteers, Propionic Acidemia, Methylmalonic Acidemia

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BBP-671
Placebo
BBP-671
Sponsored by
CoA Therapeutics, Inc., a BridgeBio company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthy Volunteers

Eligibility Criteria

15 Years - 55 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • Community Health ClinicRecruiting
  • UPMC Children's Hospital of PittsburgRecruiting
  • PPD Development, LP

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

BBP-671 for SAD

Placebo for SAD

BBP-671 for MAD

Placebo for MAD

BBP-671 for SAD Food Effect

BBP-671 for PA and MMA Patients

Arm Description

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).

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).

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).

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).

Eight (8) healthy male or female adult subjects will be randomized to receive BBP-671.

Up to sixteen (16) patients with either PA or MMA will receive BBP-671.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
March 29, 2021
Last Updated
January 11, 2023
Sponsor
CoA Therapeutics, Inc., a BridgeBio company
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1. Study Identification

Unique Protocol Identification Number
NCT04836494
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 25, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CoA Therapeutics, Inc., a BridgeBio company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers, Propionic Acidemia, Methylmalonic Acidemia, Organic Acidemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
128 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
BBP-671 for SAD
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo for SAD
Arm Type
Placebo Comparator
Arm Description
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).
Arm Title
BBP-671 for MAD
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo for MAD
Arm Type
Placebo Comparator
Arm Description
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).
Arm Title
BBP-671 for SAD Food Effect
Arm Type
Experimental
Arm Description
Eight (8) healthy male or female adult subjects will be randomized to receive BBP-671.
Arm Title
BBP-671 for PA and MMA Patients
Arm Type
Experimental
Arm Description
Up to sixteen (16) patients with either PA or MMA will receive BBP-671.
Intervention Type
Drug
Intervention Name(s)
BBP-671
Intervention Description
BBP-671, oral suspension
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matching BBP-671
Intervention Type
Drug
Intervention Name(s)
BBP-671
Intervention Description
BBP-671, tablet
Primary Outcome Measure Information:
Title
Incidence of adverse events following administration of BBP-671
Time Frame
49 days
Title
BBP-671 concentration dependent change in change from baseline in QTcF
Time Frame
49 days
Title
Pharmacokinetic Assessments: Cmax
Description
Time to maximum concentration (Cmax)
Time Frame
49 days
Title
Pharmacokinetic Assessments: Tmax
Description
Time to reach maximum observed plasma concentration (Tmax)
Time Frame
49 days
Title
Pharmacokinetic Assessments: t1/2
Description
Plasma decay half-life (t1/2)
Time Frame
49 days
Title
Pharmacokinetic Assessments: AUC0-tau
Description
Area under the plasma concentration-time curve (AUC0-tau)
Time Frame
49 days
Title
Pharmacokinetic Assessments: CL/F
Description
Apparent clearance (CL/F)
Time Frame
15 days
Title
Pharmacokinetic Assessments: Vz/F
Description
Apparent volume of distribution (Vz/F)
Time Frame
15 days
Title
Pharmacokinetic Assessments: CLr
Description
Renal clearance (CLr)
Time Frame
15 days
Secondary Outcome Measure Information:
Title
Food Effect: Cmax
Description
Time to maximum concentration
Time Frame
10 days
Title
Food Effect: Tmax
Description
Time to reach maximum observed plasma concentration
Time Frame
10 days
Title
Food Effect: AUC
Description
Area under the plasma concentration-time curve
Time Frame
10 days
Title
Pharmacodynamic Assessment: Whole blood, plasma, and urine biomarker concentrations will be quantified and summarized using appropriate descriptive parameters
Description
Measurement will be done using liquid chromatography-tandem mass spectrometry
Time Frame
49 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Medical Information
Phone
(650) 391-9740
Email
medinfo@coatherapeutics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
VP Clinical Development, CoA Therapeutics, Inc., a Bridgebio company
Official's Role
Study Chair
Facility Information:
Facility Name
Community Health Clinic
City
Topeka
State/Province
Indiana
ZIP/Postal Code
46571
Country
United States
Individual Site Status
Recruiting
Facility Name
UPMC Children's Hospital of Pittsburg
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Recruiting
Facility Name
PPD Development, LP
City
Austin
State/Province
Texas
ZIP/Postal Code
78744
Country
United States
Individual Site Status
Completed

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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