A Phase 2 Study to Determine the Safety and Efficacy of AIR001 in Subjects With Pulmonary Arterial Hypertension (PAH)
7 april 2014 bijgewerkt door: Aires Pharmaceuticals, Inc.
A Phase 2, Multi-Center, Open-label, Randomized, Parallel-Dose Study to Determine the Safety and Efficacy of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension (PAH)
The purpose of this study is to evaluate the safety and effectiveness of an investigational/experimental drug called AIR001.
To test the effectiveness, the study will evaluate how AIR001 affects the blood vessels in the lungs and the function of the heart. This will be done by monitoring changes in Pulmonary Vascular Resistance (PVR); from Baseline/Day 1 (start of study drug) to Week 16 of the study. PVR measures the resistance to flow in the blood vessels of the lungs. The study will include other assessments to evaluate the effect of the study drug on PAH, including measurements of exercise ability and evaluations of PAH disease symptoms.
Studie Overzicht
Toestand
Beëindigd
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
The primary objective of this study is to evaluate the efficacy of inhaled nebulized AIR001 administered, for 16 weeks, according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH), as determined by change in Pulmonary Vascular Resistance (PVR) from Baseline to Week 16 measured immediately post completion of AIR001 nebulization (as soon as feasible).
Studietype
Ingrijpend
Inschrijving (Werkelijk)
29
Fase
- Fase 2
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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New South Wales
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Darlinghurst, New South Wales, Australië, 2010
- St. Vincent's Hospital
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Queensland
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Chermside, Queensland, Australië, 4032
- The Prince Charles Hospital
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Tasmania
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Hobart, Tasmania, Australië, 7000
- Royal Hobart Hospital
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Victoria
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Melbourne, Victoria, Australië, 3004
- The Alfred Hospital
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Budapest, Hongarije, 1083
- Gottsegen Gyorgy Hungarian
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Budapest, Hongarije, 1125
- Semmelweis Karlocai
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Debrecen, Hongarije, 4032
- University of Debrecen
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Szeged, Hongarije, 6720
- University Of Szeged
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California
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La Jolla, California, Verenigde Staten, 92037
- UCSD Medical Center
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Torrance, California, Verenigde Staten, 90509
- UCLA Medical Center
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Colorado
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Aurora, Colorado, Verenigde Staten, 80045
- University of Colorado Denver
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Kentucky
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Louisville, Kentucky, Verenigde Staten, 40202
- Kentuckiana Pulmonary Associates
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Maryland
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Baltimore, Maryland, Verenigde Staten, 21201
- University of Maryland Medical Center
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, Verenigde Staten, 02111
- Tufts Medical Center
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Boston, Massachusetts, Verenigde Staten, 02118
- Boston University School of Medicine
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Missouri
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St. Louis, Missouri, Verenigde Staten, 63110-1093
- Washington University School of Medicine
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North Carolina
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Durham, North Carolina, Verenigde Staten, 27710
- Duke University Medical Center
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Ohio
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Cincinnati, Ohio, Verenigde Staten, 45267
- University of Cincinnati
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Columbus, Ohio, Verenigde Staten, 43210
- The Ohio State University Medical Center
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Pennsylvania
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Pittsburgh, Pennsylvania, Verenigde Staten, 15213
- University of Pittsburgh Medical Center
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Texas
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Dallas, Texas, Verenigde Staten, 75390
- University of Texas Southwestern Medical Center
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Houston, Texas, Verenigde Staten, 77030
- Baylor College of Medicine
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Virginia
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Falls Church, Virginia, Verenigde Staten, 22042
- INOVA Fairfax Hospital
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Wisconsin
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Milwaukee, Wisconsin, Verenigde Staten, 53215
- Aurora St. Luke's Medical Center
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar tot 75 jaar (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
Inclusion Criteria:
- Signed and dated informed consent document
- Able to comply with study procedures
Diagnosis of PAH as classified by:
- Idiopathic (IPAH) or heritable(HPAH); or
- PAH associated with CTD; Systemic Sclerosis, Limited Scleroderma, Mixed, SLE, or overlap syndrome;
- PAH associated with HIV ii. Simple, congenital shunts at least one year post repair. iii. Exposure to legal drugs, chemicals and toxins
Cardiac catheterization prior to Screening with:
- mPAP ≥ 25 mmHg (at rest);
- PCWP ≤ 15 mmHg; and
- PVR > 3 mmHg/L/min or 240 dyn.sec/cm5
A qualification cardiac catheterization, to confirm the persistence and severity of PAH, if the diagnostic catheterization was performed more than 30 days prior to Baseline
- Confirms diagnosis;
- PVR above 300 dyn.sec/cm5 to demonstrate the persistence and severity of PAH; and
- No change in disease-specific PAH therapy since the qualification catheterization used
- Newly diagnosed PAH on no disease-specific PAH therapy or previously diagnosed on oral disease-specific PAH therapy for 90 days prior with either an ETRA and/or PDE-5i
Has PFTs within 180 days prior to Baseline with no evidence of significant parenchymal lung disease defined as:
- FEV1 ≤ 70% (predicted) (pre-bronchodilators);
- FEV1/FVC ≤ 70% (pre-bronchodilators); or
- Total lung capacity < 70% (predicted).
- Has WHO/NYHA FC II- IV.
- ≥ 18 and ≤ 75 years.
- Weight ≥ 40 kg.
- Has 6MWT distance at least 50 meters.
- Had a V/Q scan or pulmonary angiogram prior to Screening that shows no evidence of thromboembolic disease
- If on the following: vasodilators (including calcium channel blockers), digoxin, spironolactone, or L-Arginine; must be on a stable dose 30 days prior to Baseline and maintained throughout the study
- If on corticosteroids, has been receiving a stable dose of ≤ 20 mg/day of prednisone (or equivalent dose, if other corticosteroid) for at least 30 days
- Women of childbearing potential must be using at least one form of medically acceptable contraception. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential. Men who are not sterile must also agree to use contraception
Exclusion Criteria:
- Participation in a device or other interventional clinical studies, within 30 days of Baseline and during study participation
- Participation in a cardio-pulmonary rehabilitation program based upon exercise within 30 days prior to Baseline and/or during the study
- Has uncontrolled systemic hypertension: SBP > 160 millimeter of mercury (mmHg) or DBP > 100 mmHg during Screening
- SBP < 90 mmHg at Screening or Baseline
- History of orthostatic hypotension or at the time of Screening; defined as a drop in SBP by ≥ 20 mmHg or DBP of ≥ 10 mmHg during Screening
History of left-sided heart disease and/or clinically significant cardiac disease, including:
- Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild;
- Pericardial constriction;
- Restrictive or congestive cardiomyopathy;
- Left ventricular ejection fraction < 40%
- Left ventricular shortening fraction < 22% by ECHO prior to Screening;
- Symptomatic coronary disease
- Significant (2+ for regurgitation) valvular disease other than TR or PR
- Acutely decompensated heart failure within 30 days prior to Baseline
- History of atrial septostomy within 180 days prior to Baseline
- History of obstructive sleep apnea (treated, untreated or resolved)
- Diagnosis of Down syndrome
- Moderate to severe hepatic impairment
- Has chronic renal insufficiency as defined by serum creatinine > 2.5 mg/dL or has an eGFR < 30 mL/min at Screening, or requires dialysis
- Has a Hgb concentration < 8.5 g/dL at Screening
Personal or family history of the following:
- Congenital or acquired methemoglobinemia;
- RBC CYPB5 reductase deficiency
- G6PD deficiency or any contraindication to receiving methylene blue
For subjects with HIV any of the following:
- Concomitant active opportunistic infections 180 days prior to Screening;
- Detectable viral load within 90 days of Screening;
- T-cell count < 200 mm3 within 90 days of Screening;
- Changes in antiretroviral regimen within 90 days of Screening;
- Using inhaled pentamidine
- Receiving chronic treatment with prostacyclin/prostacyclin analogue within 60 days of Baseline
- Requirement of intravenous inotropes within 30 days prior to Baseline
- The use of oral or topical nitrates (nitroglycerin, glyceryl trinitrate (GTN), isosorbide dinitrate, and isosorbide mononitrate) within 30 days prior to Baseline and until EOS or Termination
- Known or suspected hypersensitivity or allergic reaction to sodium nitrite or sodium nitrate
- History of malignancy within 5-years prior to Baseline
- Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation
- Has a disorder that compromises the ability to give informed consent
- Is currently pregnant or breastfeeding or intends to become pregnant
- Investigators, study staff or their immediate families
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 80mg AIR001 four times daily
80mg AIR001 nebulized four times daily for 16 weeks
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Dose arms specify dose loaded into the I-neb AAD System nebulizer
Andere namen:
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Experimenteel: 46mg AIR001 four times daily
46mg AIR001 nebulized four times daily for 16 weeks
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Dose arms specify dose loaded into the I-neb AAD System nebulizer
Andere namen:
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Experimenteel: 80mg AIR001 once daily
80mg AIR001 nebulized once daily for 16 weeks
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Dose arms specify dose loaded into the I-neb AAD System nebulizer
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Change in pulmonary vascular resistance (PVR)from baseline to week 16 assessed at peak AIR001
Tijdsspanne: 16 weeks
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The primary objective of this study is to evaluate the efficacy of inhaled nebulized AIR001 administered, for 16 weeks, according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension (PAH), as determined by change in Pulmonary Vascular Resistance (PVR) from Baseline to Week 16 measured immediately post completion of AIR001 nebulization (as soon as feasible).
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16 weeks
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Time to Clinical Worsening (TTCW), other hemodynamics, and safety
Tijdsspanne: 16 weeks
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To evaluate the effect of inhaled nebulized AIR001 administered according to 3 treatment arms (80 mg once daily, 46 mg 4 times daily, or 80 mg 4 times daily) in subjects with WHO Group 1 PAH for 16 weeks, as determined by time to the first morbidity/mortality event as defined in Time to Clinical Worsening (TTCW) assessments and change from Baseline to Week 16 in the following: Pulmonary Vascular Resistance Index (PVRI), N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP), 6-Minute Walk Distance (6MWD) assessed at peak, 6MWD assessed prior to AIR001 nebulization (trough), Cardiac Output (CO), Cardiac Index (CI), Mean Right Atrial Pressure (mRAP), WHO/NYHA Functional Class (FC), Quality of Life (QOL) as measured by Short-Form 36 (SF-36), Borg Dyspnea Index, Mean pulmonary artery pressure (mPAP), PVR measured at trough, PVR/systemic vascular resistance (SVR) ratio at trough and peak, To evaluate the safety and tolerability of AIR001 in subjects with WHO Group 1 PAH. |
16 weeks
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Onderzoekers
- Hoofdonderzoeker: Adaani E Frost, M.D., Baylor College of Medicine
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Algemene publicaties
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Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 november 2012
Primaire voltooiing (Werkelijk)
1 februari 2014
Studie voltooiing (Werkelijk)
1 februari 2014
Studieregistratiedata
Eerst ingediend
8 november 2012
Eerst ingediend dat voldeed aan de QC-criteria
9 november 2012
Eerst geplaatst (Schatting)
12 november 2012
Updates van studierecords
Laatste update geplaatst (Schatting)
9 april 2014
Laatste update ingediend die voldeed aan QC-criteria
7 april 2014
Laatst geverifieerd
1 april 2014
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- AIR001-CS05
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