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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04836494
• Other study ID #: CoA-101
• Status: Terminated
• Phase: Phase 1
• Start date: March 25, 2021
• Est. completion date: November 20, 2023

Study information

• Verified date: December 2023
• Source: CoA Therapeutics, Inc., a BridgeBio company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 79
• Est. completion date: November 20, 2023
• Est. primary completion date: November 20, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acidosis
• Amino Acid Metabolism, Inborn Errors
• Healthy Volunteers
• Methylmalonic Acidemia
• Organic Acidemia
• Propionic Acidemia

Intervention

Drug:
• BBP-671
BBP-671, oral suspension
• Placebo
Placebo matching BBP-671
• BBP-671
BBP-671, tablet

Locations

Country	Name	City	State
United States	PPD Development, LP	Austin	Texas
United States	UPMC Children's Hospital of Pittsburg	Pittsburgh	Pennsylvania
United States	Community Health Clinic	Topeka	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
CoA Therapeutics, Inc., a BridgeBio company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events following administration of BBP-671		49 days
Primary	BBP-671 concentration dependent change in change from baseline in QTcF		49 days
Primary	Pharmacokinetic Assessments: Cmax	Time to maximum concentration (Cmax)	49 days
Primary	Pharmacokinetic Assessments: Tmax	Time to reach maximum observed plasma concentration (Tmax)	49 days
Primary	Pharmacokinetic Assessments: t1/2	Plasma decay half-life (t1/2)	49 days
Primary	Pharmacokinetic Assessments: AUC0-tau	Area under the plasma concentration-time curve (AUC0-tau)	49 days
Primary	Pharmacokinetic Assessments: CL/F	Apparent clearance (CL/F)	15 days
Primary	Pharmacokinetic Assessments: Vz/F	Apparent volume of distribution (Vz/F)	15 days
Primary	Pharmacokinetic Assessments: CLr	Renal clearance (CLr)	15 days
Secondary	Food Effect: Cmax	Time to maximum concentration	10 days
Secondary	Food Effect: Tmax	Time to reach maximum observed plasma concentration	10 days
Secondary	Food Effect: AUC	Area under the plasma concentration-time curve	10 days
Secondary	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	49 days