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

Phase 1

Terminated

• Conditions: Healthy Volunteers; Propionic Acidemia; Methylmalonic Acidemia; Organic Acidemia
• Interventions: Drug: Placebo; Drug: BBP-671

• Registration Number: NCT04836494
• Lead Sponsor: CoA Therapeutics, Inc., a BridgeBio company

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.

Study Timeline

• Study Start: 2021-03-25
• Study First Submitted: 2021-03-29
• Study First Submitted QC: 2021-04-05
• Study First Posted: 2021-04-08
• Primary Completion: 2023-11-20
• Study Completion: 2023-11-20
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-20
• Last Update Posted: 2023-12-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 79

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo for SAD	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).
Placebo for MAD	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).
BBP-671 for MAD	BBP-671	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).
BBP-671 for PA and MMA Patients	BBP-671	Up to sixteen (16) patients with either PA or MMA will receive BBP-671.
BBP-671 for SAD	BBP-671	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).
BBP-671 for SAD Food Effect	BBP-671	Eight (8) healthy male or female adult subjects will be randomized to receive BBP-671.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (3)

UPMC Children's Hospital of Pittsburg; 🇺🇸 Pittsburgh, Pennsylvania, United States

Community Health Clinic; 🇺🇸 Topeka, Indiana, United States

PPD Development, LP; 🇺🇸 Austin, Texas, United States