Clinical trial NCT04836494: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Volunteers
Propionic Acidemia
Methylmalonic Acidemia
Organic Acidemia
Lead sponsor: CoA Therapeutics, Inc., a BridgeBio company
Sponsor class: INDUSTRY
First posted: 2021-04-08
Enrollment: 79
Sex: ALL
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Incidence of adverse events following administration of BBP-671
timeFrame: 49 days
measure: BBP-671 concentration dependent change in change from baseline in QTcF
timeFrame: 49 days
measure: Pharmacokinetic Assessments: Cmax
timeFrame: 49 days
measure: Pharmacokinetic Assessments: Tmax
timeFrame: 49 days
measure: Pharmacokinetic Assessments: t1/2
timeFrame: 49 days
measure: Pharmacokinetic Assessments: AUC0-tau
timeFrame: 49 days
measure: Pharmacokinetic Assessments: CL/F
timeFrame: 15 days
measure: Pharmacokinetic Assessments: Vz/F
timeFrame: 15 days
measure: Pharmacokinetic Assessments: CLr
timeFrame: 15 days
Secondary outcomes:
measure: Food Effect: Cmax
timeFrame: 10 days
measure: Food Effect: Tmax
timeFrame: 10 days
measure: Food Effect: AUC
timeFrame: 10 days
measure: Pharmacodynamic Assessment: Whole blood, plasma, and urine biomarker concentrations will be quantified and summarized using appropriate descriptive parameters
timeFrame: 49 days
Other outcomes:
Locations:
city: Topeka
country: United States
facility: Community Health Clinic
state: Indiana
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburg
state: Pennsylvania
city: Austin
country: United States
facility: PPD Development, LP
state: Texas
Study officials:
affiliation: VP Clinical Development, CoA Therapeutics, Inc., a Bridgebio company
name: Medical Monitor
role: STUDY_CHAIR
References: