ABI-009, an mTOR Inhibitor, for Patients With Severe Pulmonary Arterial Hypertension
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| ClinicalTrials.gov Identifier: NCT02587325 |
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Recruitment Status :
Recruiting
First Posted : October 27, 2015
Last Update Posted : February 7, 2019
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Sponsor:
Aadi, LLC
Information provided by (Responsible Party):
Aadi, LLC
- Study Details
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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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 25 participants |
| 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 : | August 2019 |
| Estimated Study Completion Date : | December 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Pulmonary Hypertension
| Arm | Intervention/treatment |
|---|---|
| Experimental: ABI-009 |
Drug: ABI-009, nab-rapamycin, albumin-bound rapamycin
ABI-009 |
Primary Outcome Measures :
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 16 weeks ]
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 year 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)
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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 ≤ 12 mm
- PVR >5 mmHg/L/min (Woods unit)
- Functional class III or IV according to the WHO set forth at the Dana Point Classification 2008 Meeting
- On 2 or more specific standard PAH therapies (for ≥ 12 consecutive weeks and at stable dose for ≥ 8 consecutive weeks) unless documented inability to tolerate 2 standard therapies
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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 (< 3 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
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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 (Cockroft formula) ≤ 60 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
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
| Contact: Berta Grigorian | 818-416-8378 | bgrigorian@aadibio.com |
Locations
| United States, Arizona | |
| University of Arizona | Not yet 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 | Not yet recruiting |
| Indianapolis, Indiana, United States, 46202 | |
| Contact: Annie Thorpe 317-962-9904 Athorp2@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: Mary Kunkel 412-647-4463 kunkelme@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
| Responsible Party: | Aadi, LLC |
| ClinicalTrials.gov Identifier: | NCT02587325 History of Changes |
| Other Study ID Numbers: |
PAH-001 |
| First Posted: | October 27, 2015 Key Record Dates |
| Last Update Posted: | February 7, 2019 |
| Last Verified: | February 2019 |
| 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 Hypertension, Pulmonary Familial Primary Pulmonary Hypertension Vascular Diseases Cardiovascular Diseases Lung Diseases Respiratory Tract Diseases Sirolimus Everolimus |
Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antineoplastic Agents Antifungal Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |