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ABI-009, an mTOR Inhibitor, for Patients With Severe Pulmonary Arterial Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02587325
Recruitment Status : Recruiting
First Posted : October 27, 2015
Last Update Posted : October 11, 2021
Sponsor:
Information provided by (Responsible Party):
Aadi, LLC

Study Description
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Brief Summary:
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. ABI-009 is an albumin-bound mTOR inhibitor with improved penetration in lung tissue.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Drug: ABI-009, nab-rapamycin, albumin-bound rapamycin Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Clinical Trial of ABI-009, an mTOR Inhibitor, for Patients With Severe Pulmonary Arterial Hypertension (PAH)
Actual Study Start Date : April 1, 2017
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: ABI-009 Drug: ABI-009, nab-rapamycin, albumin-bound rapamycin
ABI-009


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 16 weeks ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02587325


Contacts
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Contact: Berta Grigorian 818-416-8378 bgrigorian@aadibio.com

Locations
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United States, Arizona
University of Arizona Recruiting
Tucson, Arizona, United States, 85724
Contact: Valerie Bloss    520-626-8305    vbloss@email.arizona.edu   
United States, California
Harbor-UCLA Medical Center Recruiting
Torrance, California, United States, 90502
Contact: Ronald Oudiz, MD    310-222-3560    roudiz@labiomed.org   
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Shawna Prange    317-962-7459    sprange@iuhealth.org   
United States, Maryland
National Institutes of Health Recruiting
Bethesda, Maryland, United States, 20892
Contact: Keshia Thompson    301-827-6135    keshia.thompson@nih.gov   
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Kristin Shoemaker, RN, BSN, CCRC    412-692-2769    shoeka@UPMC.EDU   
United States, Virginia
Inova Fairfax Hospital Recruiting
Falls Church, Virginia, United States, 22042
Contact: Vinita Gupta    703-776-3697    vinita.gupta@inova.org   
Sponsors and Collaborators
Aadi, LLC
More Information
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Responsible Party: Aadi, LLC
ClinicalTrials.gov Identifier: NCT02587325    
Other Study ID Numbers: PAH-001
First Posted: October 27, 2015    Key Record Dates
Last Update Posted: October 11, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Pulmonary Arterial Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Sirolimus
 Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs