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

CoA Therapeutics

Status and phase

Terminated

Phase 1

Conditions

Organic Acidemia

Healthy Volunteers

Methylmalonic Acidemia

Propionic Acidemia

Treatments

Drug: BBP-671

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT04836494

CoA-101

Details and patient eligibility

About

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.

Full 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.

Enrollment

79 patients

Sex

All

Ages

15 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Triple Blind

79 participants in 6 patient groups, including a placebo group

BBP-671 for SAD

Experimental group

Description:

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).

Treatment:

Drug: BBP-671

Placebo for SAD

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo

BBP-671 for MAD

Experimental group

Description:

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).

Treatment:

Drug: BBP-671

Placebo for MAD

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo

BBP-671 for SAD Food Effect

Experimental group

Description:

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

Treatment:

Drug: BBP-671

BBP-671 for PA and MMA Patients

Experimental group

Description:

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