Phase 1/1b Study With Nab-sirolimus for Patients With Severe Pulmonary Arterial Hypertension

October 7, 2024 updated by: Aadi Bioscience, Inc.

A Phase 1/1b Clinical Trial of ABI-009, an mTOR Inhibitor, for Patients With Severe Pulmonary Arterial Hypertension (PAH)

mTOR activation has been shown to be relevant in the development and progression of pulmonary hypertension. Inhibition of mTOR has been shown to reverse or regress pulmonary hypertension in animal models. nab-Sirolimus (also known as ABI-009, nab-rapamycin) is an albumin-bound mTOR inhibitor with improved penetration in lung tissue.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

nab-Sirolimus, an mTOR inhibitor, is a novel formulation of albumin-bound sirolimus nanoparticles and has produced encouraging results in oncology at doses up to 100 mg/m2 given once weekly IV. This study is aimed to determine the optimal clinial dose of once weekly IV nab-sirolimus in patients with PAH and safety of 16 weeks of therapy (Phase 1, Dose finding Safety Part) followed optionally by up to 32 weeks of therapy (Extension Part).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • University of Arizona
    • California
      • Torrance, California, United States, 90502
        • Harbor-UCLA Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female age >18 years old with a current diagnosis of WHO Group 1 PAH including idiopathic pulmonary arterial hypertension (IPAH), heritable pulmonary arterial hypertension (HPAH), drug and toxin induced PAH, or PAH associated with connective tissue disease, or congenital heart defects (repaired greater than 1 year prior to Screening)

  • Must meet following hemodynamic definition prior to initiation of study drug

    • Mean PAP of ≥ 25 mm Hg
    • PCWP or left ventricular end diastolic pressure (LVEDP) of ≤ 15 mm
    • PVR > 5 mmHg/L/min (Woods unit)
  • Functional class II or III according to the WHO set forth at the Dana Point Classification 2008 Meeting
  • On 2 or more specific standard PAH therapies (for ≥ 8 consecutive weeks and at stable dose for ≥ 4 consecutive weeks) unless documented inability to tolerate 2 standard therapies

  • Meet the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to screening, performed with or without bronchodilation:

    • Forced expiratory volume in one second (FEV1) ≥ 55% of predicted normal
    • FEV1:forced vital capacity (FVC) ratio ≥ 0.60
  • 6MWD ≥150 meters and ≤450 meters
  • Negative serum pregnancy test
  • Female of childbearing age either surgically sterilized or using acceptable method of contraception
  • Ability to provide written informed consent by the patient or legal guardian

Exclusion criteria:

  • History of heart disease including left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant valvular constrictive or atherosclerotic heart disease (myocardial infarction, angina, cerebrovascular accident)
  • History of malignancy in 2 years prior to enrollment
  • Pulmonary hypertension (PH) belonging to groups 2 to 5 of the 2013 Nice classification
  • Current or recent (< 3 months) use of inotropic or vasopressor agents for the treatment of PAH
  • Recent (< 2 months) PAH related hospital admission
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition including macrolide (eg, azithromycin, clarithromycin, dirithromycin, and erythromycin) and ketolide antibiotics
  • Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy
  • Uncontrolled hyperlipidemia (serum triglyceride ≥300 mg/dL)
  • Serum cholesterol ≥350 mg/dL
  • Surgery within 3 months of start date of study drug

  • Baseline cytopenias:

    • Absolute Neutrophil Count ≤ 1.5 x 109/L
    • Hemoglobin ≤ 9 g/dL
    • Platelet count < 100,000/mm3
  • Baseline liver disease: ALT/AST, total bilirubin, alkaline phosphatase >1.5 x ULN
  • Baseline renal disease: creatinine >1.5 ULN and/or creatinine clearance (Cockcroft formula) ≤ 30 mL/min
  • Inability to attend scheduled clinic visits
  • Prior use of study drug within previous 6 months from enrollment
  • Previous lung transplant
  • Naïve to available standard PAH therapy
  • Concomitant genetic or acquired immunosuppressive diseases (such as HIV, AIDS)
  • Uncontrolled intercurrent illness that in the opinion of the investigator would limit compliance and tolerance to study requirements (eg, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, uncontrolled hypertension, coronary artery disease, or psychiatric illness/social situations)
  • Concomitant enrollment in another investigational treatment protocol for PAH
  • Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfanide) within the 14 days prior to receiving the first dose of ABI-009

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Nab-Sirolimus Dose Cohort 1
nab-Sirolimus Dose Cohort 1 at 10 mg/m2, given once weekly intravenously for 16 weeks. The initial 16-Week treatment was followed optionally by up to 32 weeks of therapy (Extension Part)
Drug: nab-sirolimus
nab-sirolimus is an mTOR inhibitor
Other Names:
  • ABI-009, nab-rapamycin
Experimental: Nab-Sirolimus Dose Cohort 2
nab-Sirolimus Dose Cohort 2 at 1.0 mg/m2, given once weekly intravenously for 16 weeks. The initial 16-Week treatment was followed optionally by up to 32 weeks of therapy (Extension Part)
Drug: nab-sirolimus
nab-sirolimus is an mTOR inhibitor
Other Names:
  • ABI-009, nab-rapamycin
Experimental: Nab-Sirolimus Dose Cohort 3
nab-Sirolimus Dose Cohort 3 at 2.5 mg/m2, given once weekly intravenously for 16 weeks. The initial 16-Week treatment was followed optionally by up to 32 weeks of therapy (Extension Part)
Drug: nab-sirolimus
nab-sirolimus is an mTOR inhibitor
Other Names:
  • ABI-009, nab-rapamycin
Experimental: Nab-Sirolimus Dose Cohort 4
nab-Sirolimus Dose Cohort 4 at 5.0 mg/m2, given once weekly intravenously for 16 weeks. The initial 16-Week treatment was followed optionally by up to 32 weeks of therapy (Extension Part)
Drug: nab-sirolimus
nab-sirolimus is an mTOR inhibitor
Other Names:
  • ABI-009, nab-rapamycin
Experimental: Nab-Sirolimus Dose Cohort 5
nab-Sirolimus Dose Cohort 5 at 7.5 mg/m2, given once weekly intravenously for 16 weeks. The initial 16-Week treatment was followed optionally by up to 32 weeks of therapy (Extension Part)
Drug: nab-sirolimus
nab-sirolimus is an mTOR inhibitor
Other Names:
  • ABI-009, nab-rapamycin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose-limiting Toxicities
Time Frame: 16 weeks
A dose-limiting toxicity (DLT) was defined as a study drug-related Grade ≥3 hematologic AE or persistent intolerable nonhematologic AE of any grade that occurred during the first 4 weeks of treatment, requiring dose reduction or permanent discontinuation of the study drug, in the opinion of the Investigator. The number and percent of patients with a DLT were to be reported by dose cohorts in the Phase 1 dose finding part of the study if any were observed in the study.
16 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume)
Time Frame: 17 Weeks
Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in RHC based on Central Lab Analysis (Pulmonary vascular resistance, Cardiac Output, Cardiac Index, Stroke Volume)
17 Weeks
6-minute Walk Distance (6MWD)
Time Frame: 17 Weeks
Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in 6MWD
17 Weeks
N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP)
Time Frame: 17 Weeks
Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in NT Pro-BNP
17 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Aadi Bioscience, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marc Simon, MD, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 16, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 16, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 23, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 26, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 27, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 25, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PAH-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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