Pulmonary HypertensionPhase 1NCT02587325
Phase 1/1b Study With Nab-sirolimus for Patients With Severe Pulmonary Arterial Hypertension
A Phase 1 study testing nab-sirolimus in people with Pulmonary Hypertension, run by Aadi Bioscience, Inc. at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- nab-sirolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 6 sitesUnited States
- Study dates
- 1 Apr 2017to 16 Sep 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
National Institutes of Health
Bethesda, Maryland, 20892
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Indiana University
Indianapolis, Indiana, 46202
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Harbor-UCLA Medical Center
Torrance, California, 90502
University of Arizona
Tucson, Arizona, 85724
About this study
Official title: 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.
Read the 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).
- Conditions
- Pulmonary Hypertension
- Being tested
- nab-sirolimus
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nab-sirolimusDrug
Also called ABI-009, nab-rapamycin
nab-sirolimus is an mTOR inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Nab-Sirolimus Dose Cohort 1 | Experimental | 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) Receives: Drug: nab-sirolimus |
| Nab-Sirolimus Dose Cohort 2 | Experimental | 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) Receives: Drug: nab-sirolimus |
| Nab-Sirolimus Dose Cohort 3 | Experimental | 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) Receives: Drug: nab-sirolimus |
| Nab-Sirolimus Dose Cohort 4 | Experimental | 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) Receives: Drug: nab-sirolimus |
| Nab-Sirolimus Dose Cohort 5 | Experimental | 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) Receives: Drug: nab-sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting Toxicities
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.
Measured: 16 weeks
Secondary outcomes (3)
Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume)
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)
Measured: 17 Weeks
6-minute Walk Distance (6MWD)
Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in 6MWD
Measured: 17 Weeks
N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP)
Median Percent Change from Baseline to Week 17 (after 16 weeks of treatment) in NT Pro-BNP
Measured: 17 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2015 (estimated)
- Study start1 Apr 2017
- Primary completion16 Aug 2022
- Study completion16 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary HypertensionStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aadi Bioscience, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marc Simon, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02587325
- Sponsor's protocol ID
- PAH-001
- Status last verified
- Oct 2024
- First submitted
- 23 Oct 2015
- Last updated
- 25 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b Clinical Trial of ABI-009, an mTOR Inhibitor, for Patients With Severe Pulmonary Arterial Hypertension (PAH)
- ClinicalTrials.gov ID
- NCT02587325
- Acronym / sponsor ID
- PAH-001
- Conditions
- Pulmonary Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Aadi Bioscience, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 16 Aug 2022 (actual)
- Study completion
- 16 Sep 2022 (actual)
- First posted
- 27 Oct 2015 (estimated)
- Results
- Posted 25 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Nab-Sirolimus Dose Cohort 1 | Experimental | Drug: nab-sirolimusnab-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) |
| Nab-Sirolimus Dose Cohort 2 | Experimental | Drug: nab-sirolimusnab-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) |
| Nab-Sirolimus Dose Cohort 3 | Experimental | Drug: nab-sirolimusnab-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) |
| Nab-Sirolimus Dose Cohort 4 | Experimental | Drug: nab-sirolimusnab-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) |
| Nab-Sirolimus Dose Cohort 5 | Experimental | Drug: nab-sirolimusnab-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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
- 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:
Key exclusion criteria (24 listed)
- 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
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 |
|---|---|---|
| nab-sirolimusAlso: ABI-009, nab-rapamycinnab-sirolimus is an mTOR inhibitor | Drug | Nab-Sirolimus Dose Cohort 1, Nab-Sirolimus Dose Cohort 2, Nab-Sirolimus Dose Cohort 3, Nab-Sirolimus Dose Cohort 4, Nab-Sirolimus Dose Cohort 5 |
Primary outcome
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.
3 secondary outcomes
Right Heart Catheterization Based on Central Lab Analysis (Pulmonary Vascular Resistance, Cardiac Output, Cardiac Index, Stroke Volume)
Time frame: 17 Weeks
6-minute Walk Distance (6MWD)
Time frame: 17 Weeks
N-terminal Pro-brain Natriuretic Peptide (NT Pro-BNP)
Time frame: 17 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Marc Simon, MD principal investigator
University of California, San Francisco
6 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 nab-sirolimus in people with Pulmonary Hypertension, run by Aadi Bioscience, Inc. at 6 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 24 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: finished, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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. 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?
Yes. Results are posted in the registry (first posted 25 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Dose-limiting Toxicities (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Nov 2024.