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

NCT04836494 | Terminated Phase 1 FDA Drug

• 1 other identifier: CoA-101
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 3

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.

Conditions

Healthy Volunteers; Propionic Acidemia; Methylmalonic Acidemia; Organic Acidemia

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (4)

• Food Effect: Cmax

  10 days

• Food Effect: Tmax

  10 days

• Food Effect: AUC

  10 days

• Pharmacodynamic Assessment: Whole blood, plasma, and urine biomarker concentrations will be quantified and summarized using appropriate descriptive parameters

  49 days

Study Arms (6)

BBP-671 for SAD

EXPERIMENTAL

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

Placebo for SAD

PLACEBO COMPARATOR

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

BBP-671 for MAD

EXPERIMENTAL

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

Placebo for MAD

PLACEBO COMPARATOR

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

BBP-671 for SAD Food Effect

EXPERIMENTAL

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

Drug: BBP-671

BBP-671 for PA and MMA Patients

EXPERIMENTAL

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

Drug: BBP-671

Interventions

BBP-671 DRUG

BBP-671, oral suspension

BBP-671 for MAD; BBP-671 for SAD; BBP-671 for SAD Food Effect

Placebo DRUG

Placebo matching BBP-671

Placebo for MAD; Placebo for SAD

Eligibility Criteria

• Age: 15 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• CoA Therapeutics, Inc., a BridgeBio company: lead

Study Sites (3)

Community Health Clinic

Topeka, Indiana, 46571, United States

Location

UPMC Children's Hospital of Pittsburg

Pittsburgh, Pennsylvania, 15224, United States

Location

PPD Development, LP

Austin, Texas, 78744, United States

Location

Related Publications (1)

• 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.

  PMID: 37875310 DERIVED

MeSH Terms

Conditions

Propionic Acidemia; Methylmalonic acidemia

Condition Hierarchy (Ancestors)

Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Medical Monitor

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 8, 2021
• Study Start: March 25, 2021
• Primary Completion: November 20, 2023
• Study Completion: November 20, 2023
• Last Updated: December 21, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)