Healthy VolunteersPhase 1NCT04836494

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 Phase 1 study testing BBP-671 in people with Healthy Volunteers and Propionic Acidemia, run by CoA Therapeutics, Inc., a BridgeBio company at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 15 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers, Propionic Acidemia, Methylmalonic Acidemia
What is being tested?: BBP-671
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 79 participants
Where: 3 sitesUnited States
Study dates: 25 Mar 2021to 20 Nov 2023
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 15 to 55 years
All sexes
Healthy volunteers accepted
Child, Adult

Who may be able to join

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

Show all 14Show fewer

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.

Who cannot join

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

Show all 31Show fewer

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
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 locations and contacts

3 sites in 1 country.

United States3 sites

PPD Development, LP
Austin, Texas, 78744
UPMC Children's Hospital of Pittsburg
Pittsburgh, Pennsylvania, 15224
Community Health Clinic
Topeka, Indiana, 46571

Other trials in United States

About this study

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

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.

Read the 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.

Conditions: Healthy Volunteers, Propionic Acidemia, Methylmalonic Acidemia, Organic Acidemia
Being tested: BBP-671, Placebo
Medical subject headings: Propionic Acidemia, Methylmalonic acidemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BBP-671Drug
BBP-671, oral suspension
PlaceboDrug
Placebo matching BBP-671
BBP-671Drug
BBP-671, tablet

Study groups in NCT04836494
Study group	Role	What they receive
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). Receives: 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). Receives: 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). Receives: 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). Receives: Drug: Placebo
BBP-671 for SAD Food Effect	Experimental	Eight (8) healthy male or female adult subjects will be randomized to receive BBP-671. Receives: 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. Receives: Drug: BBP-671

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (4)

Food Effect: Cmax
Time to maximum concentration
Measured: 10 days
Food Effect: Tmax
Time to reach maximum observed plasma concentration
Measured: 10 days
Food Effect: AUC
Area under the plasma concentration-time curve
Measured: 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
Measured: 49 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Mar 202120 Nov 2023

First posted8 Apr 2021
Study start25 Mar 2021
Primary completion20 Nov 2023
Study completion20 Nov 2023

Why it stopped: Slow recruitment

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 79 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04836494
Sponsor's protocol ID: CoA-101
Status last verified: Dec 2023
First submitted: 29 Mar 2021
Last updated: 21 Dec 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 37875310

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 21 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04836494
Acronym / sponsor ID: CoA-101
Conditions: Healthy Volunteers, Propionic Acidemia, Methylmalonic Acidemia, Organic Acidemia
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Slow recruitment
Enrolment: 79 participants (actual)
Lead sponsor: CoA Therapeutics, Inc., a BridgeBio companyIndustry (pharma, biotech, devices)
Study start: 25 Mar 2021 (actual)
Primary completion: 20 Nov 2023 (actual)
Study completion: 20 Nov 2023 (actual)
First posted: 8 Apr 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 6

Arm	Type	Receives
BBP-671 for SAD	Experimental	Drug: BBP-671The 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).
Placebo for SAD	Placebo comparator	Drug: PlaceboThe 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).
BBP-671 for MAD	Experimental	Drug: BBP-671The 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).
Placebo for MAD	Placebo comparator	Drug: PlaceboThe 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 SAD Food Effect	Experimental	Drug: BBP-671Eight (8) healthy male or female adult subjects will be randomized to receive BBP-671.
BBP-671 for PA and MMA Patients	Experimental	Drug: BBP-671Up to sixteen (16) patients with either PA or MMA will receive BBP-671.

Who may qualify

Ages: 15 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (14 listed)

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

Key exclusion criteria (31 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BBP-671BBP-671, oral suspension	Drug	BBP-671 for MAD, BBP-671 for SAD, BBP-671 for SAD Food Effect
PlaceboPlacebo matching BBP-671	Drug	Placebo for MAD, Placebo for SAD
BBP-671BBP-671, tablet	Drug	BBP-671 for PA and MMA Patients

Primary outcome

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

4 secondary outcomes

Food Effect: Cmax
Time frame: 10 days
Food Effect: Tmax
Time frame: 10 days
Food Effect: AUC
Time frame: 10 days
Pharmacodynamic Assessment: Whole blood, plasma, and urine biomarker concentrations will be quantified and summarized using appropriate descriptive parameters
Time frame: 49 days

Results and safety

The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2023.
Derived from this study: PubMed 37875310Subramanian 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study chair

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

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BBP-671 in people with Healthy Volunteers and Propionic Acidemia, run by CoA Therapeutics, Inc., a BridgeBio company at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events following administration of BBP-671 (time frame: 49 days). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04836494, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2023.