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

NCT ID: NCT04836494

Last Updated: 2023-12-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-25
• Study Completion Date: 2023-11-20

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.

Conditions

Healthy Volunteers; Propionic Acidemia; Methylmalonic Acidemia; Organic Acidemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

BBP-671

Intervention Type: DRUG

BBP-671, oral suspension

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching BBP-671

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).

Group Type: EXPERIMENTAL

BBP-671

Intervention Type: DRUG

BBP-671, oral suspension

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching BBP-671

BBP-671 for SAD Food Effect

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

Group Type: EXPERIMENTAL

BBP-671

Intervention Type: DRUG

BBP-671, oral suspension

BBP-671 for PA and MMA Patients

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

Group Type: EXPERIMENTAL

BBP-671

Intervention Type: DRUG

BBP-671, tablet

Interventions

BBP-671

BBP-671, oral suspension

Intervention Type: DRUG

Placebo

Placebo matching BBP-671

Intervention Type: DRUG

BBP-671

BBP-671, tablet

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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.

• 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)

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

CoA Therapeutics, Inc., a BridgeBio company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_CHAIR

VP Clinical Development, CoA Therapeutics, Inc., a Bridgebio company

Locations

Community Health Clinic

Topeka, Indiana, United States

UPMC Children's Hospital of Pittsburg

Pittsburgh, Pennsylvania, United States

PPD Development, LP

Austin, Texas, United States

Countries

United States

References

Subramanian C, Frank MW, Sukhun R, Henry CE, Wade A, Harden ME, Rao S, Tangallapally R, Yun MK, White SW, Lee RE, Sinha U, Rock CO, Jackowski S. Pantothenate Kinase Activation Restores Brain Coenzyme A in a Mouse Model of Pantothenate Kinase-Associated Neurodegeneration. J Pharmacol Exp Ther. 2024 Jan 2;388(1):171-180. doi: 10.1124/jpet.123.001919.

Reference Type: DERIVED

PMID: 37875310 (View on PubMed)

Other Identifiers

CoA-101

Identifier Type: -

Identifier Source: org_study_id