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

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.

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.

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)