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.

Study Overview

• Status: Terminated
• Conditions: Healthy Volunteers; Propionic Acidemia; Methylmalonic Acidemia; Organic Acidemia
• Intervention / Treatment: Drug: BBP-671; Drug: BBP-671; Drug: Placebo

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: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

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

Eligibility Criteria

• 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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Food Effect: Cmax	Time to maximum concentration	10 days
Food Effect: Tmax	Time to reach maximum observed plasma concentration	10 days
Food Effect: AUC	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	Measurement will be done using liquid chromatography-tandem mass spectrometry	49 days

Collaborators and Investigators

• Sponsor: CoA Therapeutics, Inc., a BridgeBio company
• Investigators: Study Chair: Medical Monitor, VP Clinical Development, CoA Therapeutics, Inc., a Bridgebio company

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2021
• Primary Completion (Actual): November 20, 2023
• Study Completion (Actual): November 20, 2023

Study Registration Dates

• First Submitted: March 29, 2021
• First Submitted That Met QC Criteria: April 5, 2021
• First Posted (Actual): April 8, 2021

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Acid-Base Imbalance; Acidosis; Propionic Acidemia; Amino Acid Metabolism, Inborn Errors
• Other Study ID 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