Research

Research Program - COPD and Alpha-1

The UCLA COPD and Alpha-1 research program links patients, providers, and scientists to further the understanding and treatment of these conditions. UCLA conducts several types of research in these areas:

• Basic science research – Experimental work carried out in a laboratory helps the center to better understand the fundamental cellular mechanisms of COPD and related conditions like Alpha-1.
• Clinical and translational research – Clinical research includes both observational studies and clinical trials that use the knowledge gained in basic research to study the benefits of new treatments.
• Health services research – Health services research uses techniques to better understand how patients experience their conditions and their healthcare in the real world, and to improve the way health systems and providers take care of their patients.

Patients are eligible to participate in a research study at UCLA whether or not their doctors are here at UCLA. Our study team may reach out to patients to see if they are interested in participating in studies if they have expressed interest in being a part of our research program. Participation is entirely voluntary and choosing whether or not to participate in research in no way influences patient care. Funding for our research studies comes from a variety of sources, both public and private.

To become involved in a research study

Speak with the physicians in the UCLA Chronic Obstructive Pulmonary Disease and Alpha-1 Anti-Trypsin Deficiency Program about potential studies. For additional information, you can also call the study coordinators in the COPD-Alpha 1 Research Program at 310-825-2616 or e-mail [email protected] for Alpha-1 studies or [email protected] for COPD-related studies.

Upcoming and Currently Enrolling Studies

The American Lung Association (ALA) Lung Health Cohort

Sponsor: National Heart, Lung and Blood institute (NHLBI) or National Health Institute (NIH), together with ALA

This research is being done to find out why some people have better lung function than others as young adults during the period of peak lung health (ages 25 to 35 years old). This will allow us to come up with ideas about how to promote the best possible lung function in you adults and also prevent and treat lung diseases like asthma, chronic obstructive pulmonary disease (COPD, also called emphysema or bronchitis), pulmonary fibrosis (scarring in the lungs), and lung cancer.   A main focus of the study is to identify modifiable characteristics (i.e. behaviors that can be changed such as smoking, vaping and diet), environmental exposures (e.g. pollution such as car exhaust, allergies such as pet dander) that affect lung function and risk of future lung disease. Study participation stipend provided.

Eligibility: healthy individuals between the ages of 25 to 35 years with no history of chronic (i.e. long-lasting) lung diseases other than mild asthma and no history of cardiovascular disease can join this study. Participation and all related costs will be reimbursed.

If interested, please contact at: [email protected] 

SOURCE – SPIROMICS Understanding the Origins of Early COPD

Sponsor: National Heart, Lung and Blood institute (NHLBI) or National Health Institute (NIH)

The Early COPD Study is studying the clinical characteristics and biological underpinnings of early chronic obstructive pulmonary disease (COPD). We will use 12 clinical centers (all current SPIROMICS sites) to enroll a total of 600 participants ages 35-55 years old, both sexes, all races and ethnicities. The participants will include never-smokers (n=20) and GOLD 0-2 participants (n=580). All never-smokers and 80 of the GOLD 1-2 participants will also undergo bronchoscopy in a sub-study of airway epithelial biomarkers. Participation and all related costs will be reimbursed. Study participation stipend provided. Associated with an additional reimbursement, a subgroup of enrolled participants will undergo research bronchoscopy.

Eligibility: healthy or COPD-diagnosed individuals 35- 55 years of age, with ≥10 pack-years smoking history, and with either: (a) mild to moderate airflow obstruction; or (b) respiratory symptoms in the absence of airflow obstruction.

If interested, please contact at: [email protected] 

Alpha-1 Antitrypsin Disease Cohort: Longitudinal Biomarker Study of Disease (A1BC)

Sponsor: National Heart, Lung and Blood institute (NHLBI) and Alpha-1 Foundation

Progression of lung disease in patients with Alpha-1 Anti-trypsin deficiency is variable and while some patients may have stable lung function over many years, some progress and deteriorate rapidly. Currently there are no predictors that would help identify patient at risk of rapid deterioration. The aim of this study is to identify markers and features in CT imaging that may allow identification of these patients early before deterioration. To achieve this, the study will follow a cohort of patients with confirmed Alpha-1 Anti-trypsin deficiency and lung disease and measure a number of biomarkers in blood and sputum and obtain high resolution CT scans at baseline and again three years later. If the study is able to determine markers that allow the identification of patients at risk early, the investigator may be able to study early interventions in later studies and possibly find ways to avoid serious complications. Patients will be followed longitudinally to assess deterioration of lung function. Study participation stipend provided.

Study procedures include: Review of medical history and medication history, blood draw, complete Pulmonary Function Test (PFT), induced sputum (at some sites), completion of questionnaires and CT Chest scan. All of the mentioned procedures above will be performed on enrollment and repeated at 18 months and 36 months, with the exception of monthly Alpha- net exacerbation questionnaires.

Eligibility: Individuals age 18 years and older with known Alpha-1 Anti-trypsin deficiency (PiZZ)

If interested, please contact: [email protected]

Doxycycline for Emphysema in People Living With HIV (The DEPTH Trial) (DEPTH)

Sponsor: National Heart, Lung and Blood institute (NHLBI)

The purpose of this study is to determine if doxycycline will reduce progression of emphysema in people living with HIV. The secondary objectives are to examine the effects of doxycycline on change in quantity of emphysema, six minute walk distance, patient reported outcomes, ratio of forced expiratory volume in 1 second and forced vital capacity. Secondary objectives will also describe the safety and tolerability of doxycycline and determine if doxycycline is associated with development of antibiotic-resistant bacterial infections.

Eligibility: Individuals age 30 years and older; HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to the enrollment visit, and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. Current or former smoker with at least a 3 pack-year history of cigarette smoking at screening visit. Study participation stipend provided.

If interested, please contact: [email protected] 

Redwood: Two Studies to Check the Safety of Fazirsiran and Learn if Fazirsiran Can Help People With Liver Disease and Scarring (Fibrosis) Due to an Abnormal Version of Alpha-1 Antitrypsin Protein

Sponsor: TAKEDA

The main aim of this study is to learn if fazirsiran reduces liver scarring (fibrosis) compared to placebo. Other aims are to learn if fazirsiran slows down the disease worsening in the liver, to get information on how fazirsiran affects the body (called pharmacodynamics), to learn if fazirsiran reduces other liver injury (inflammation) and the abnormal Z-AAT protein in the liver, to get information on how the body processes fazirsiran (called pharmacokinetics), to test how well fazirsiran works compared with a placebo in improving measures of liver scarring including imaging and liver biomarkers (substances in the blood that the body normally makes and help show if liver function is improving, staying the same, or getting worse) as well as to check for side effects in participants treated with fazirsiran compared with those who received placebo.

Participants will either receive fazirsiran or placebo. Liver biopsies, a way of collecting a small tissue sample from the liver, will be taken twice during this study. Study participation stipend provided.

1. TAK-999 3001

Eligibility: Individuals 18-75 years of age with diagnosed Alpha-1 Anti-trypsin deficiency, PiZZ genotype and evidence of METAVIR stage F2, F3, or F4 liver fibrosis; body mass index (BMI) between 18.0 and 39.0; nonsmoker for at least 12 months before screening.

1. TAK-999 3002

Eligibility: Individuals 18-75 years of age with diagnosed Alpha-1 Anti-trypsin deficiency, PiZZ genotype and evidence of METAVIR stage F1 liver fibrosis; body mass index (BMI) between 18.0 and 39.0; nonsmoker for at least 12 months before screening.

If interested, please contact: [email protected] 

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Participants With Alpha1-Antitrypsin Deficiency

Sponsor: Grifols Therapeutics LLC

A multi-center, single-dose and repeat-dose over eight weeks, sequential cohort study to evaluate safety and tolerability as well as pharmacokinetics of two different doses of Alpha1-Proteinase Inhibitor Subcutaneous 15% administered subcutaneously in subjects with Alpha1-Antitrypsin Deficiency. 

Eligibility: Individuals 18-75 years of age diagnosed with Alpha-1 Anti-trypsin deficiency with an allelic combination of ZZ, SZ, Z(null), (null)(null), S(null), or "at-risk" alleles (subjects with "at-risk" alleles must be individually evaluated for eligibility by the Medical Monitor); post-bronchodilator forced expiratory volume (FEV1) ≥30% and <80% of predicted and FEV1/forced vital capacity (FVC) <70% (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II or III). Study participation stipend provided.

If interested, please contact: [email protected]  

Study of INBRX-101 Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (ELEVAATE)

Sponsor: Inhibrx, Inc.

This is a multicenter, double-blinded, randomized study to assess the pharmacokinetics, pharmacodynamics, immunogenicity, and safety of INBRX-101 and Plasma-Derived Alpha1-Proteinase Inhibitor (A1PI) Augmentation Therapy in participants with Alpha-1 Antitrypsin Deficiency (AATD) Emphysema. This head-to-head study is designed to test superiority of INBRX-101 at achieving a greater change from baseline in serum fAAT concentrations at steady-state trough, when compared to the current approved treatment, plasma derived A1PI augmentation therapy. Study participation stipend provided.

Eligibility: Individuals 18-80 years of age; diagnosis of AATD; Evidence of emphysema secondary to AATDFEV1 of ≥ 30% and ≤ 80% predicted at screening; Current non-smoking status.

If interested, please contact: [email protected]

Revefenacin in Acute Respiratory Insufficiency in COPD (RARICO)

Sponsor: Theravance Biopharma and Mylan Pharmaceuticals Inc

RARICO is a pragmatic, randomized, controlled, double-blinded, multi-center trial evaluating the safety and feasibility of nebulized revefenacin in comparison to nebulized ipratropium in patients with COPD and acute respiratory failure requiring invasive mechanical ventilation.

Eligibility: Adults ≥ 40 years of age; Acute respiratory failure requiring invasive mechanical ventilation; Documented history of COPD based on spirometric evidence of FEV1/FVC<70%; Smoking history >10 years (current or prior); Invasive mechanical ventilation for < 96 hours.

If interested, please contact: [email protected]

Pilot Study Evaluating the Nasal Epithelium scRNAseq changes in Chronic Bronchitis (NET-CB)

Sponsor: AMGEN

Prospective observational study in stable COPD bronchitis phenotype and or healthy controls. Goal is to identify novel cell states and biomarkers from stable COPD bronchitis phenotype from scRNAseq data from nasal epithelial cells of COPD chronic bronchitis patients vs healthy age matched controls. Participants will undergo nasal swab sampling and bloodwork in addition to collection of information about their disease state. Stipend will be provided.

Eligibility: 1) for COPD chronic bronchitis phenotype: Male sex at birth, Age 40-80 years, Former smoking status with exposure ≥ 10 pack-years,COPD defined by FEV₁/FVC<70% post-bronchodilation (acceptable historic PFT within 6 months accepted) Chronic bronchitis defined by both SGRQ criteria and MRC criteria and Symptomatic disease defined by COPD assessment tool (CAT) ≥10, and for 2) Healthy Controls: Male sex at birth, Age 40-80 years, Never-smoking tobacco, defined by <100 cigarettes in a lifetime, Normal spirometry defined by FEV₁/FVC>70% with both FEV₁ and FVC>80% predicted (Z>-1.65), Participant has Provided Informed Consent

Alpha-1 Antitrypsin Response in the Acute Phase of Systemic Inflammation

Sponsor: Takeda

Prospective observational study to enroll individuals with the PiMM genotype admitted to the inpatient medical ward with an acute respiratory infection and evidence of systemic inflammation to compare A1AT levels and functional activity in this state and upon resolution of the acute inflammatory response. We propose a targeted, prospective assessment of A1AT response in the setting of a highly inflammatory acute state as defined by the presence of the systemic inflammatory response syndrome (SIRS) secondary to acute lower respiratory infection with respiratory insufficiency. This will be compared to the steady-state level upon the resolution of inflammation. Our study aims to comprehensively compare the acute phase reaction and steady state of A1AT antigenic levels and functional activity in serum, sputum, nasal epithelium and bronchoalveolar lavage specimen

1. Eligibility: Male or female subjects who are ≥ 18 years of age at the time of informed consent,

Evidence of the SIRS defined by at least two of the following criteria: Body temperature over 38 or under 36 degrees Celsius, Heart rate greater than 90 beats/minute, Respiratory rate greater than 20 breaths/minute or partial pressure of CO2 less than 32 mmHg, Leukocyte count >12000 or <4000 cells/uL or over 10% immature forms or bands; Acute respiratory insufficiency defined by the sudden (within 96 hours of enrollment) onset of severe impairment of pulmonary gas exchange with PaO2<60mmHg or SpO2<88% on room air requiring oxygen (>2L/min nasal cannula) or ventilatory support therapies including non-invasive or invasive mechanical ventilation, Microbiologically proven or highly suspected acute infectious respiratory illness as demonstrated by an ICD-10 code for acute lower respiratory tract infection, community acquired pneumonia, bacterial or viral bronchitis or bronchopneumonia with or without acute respiratory distress syndrome, Willingness of the subject or subject’s surrogate consent for the subject to participate in the study

Ongoing Studies No Longer Enrolling

COURSE study - Tezepelumab COPD Exacerbation Study
Sponsor: Astra Zeneca

This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving triple inhaled maintenance therapy, and having had 2 or more documented COPD exacerbations in the 12 months prior to Visit 1. Approximately, 282 subjects will be randomized globally. Subjects will be stratified by region and prior number of exacerbations (2 vs. 3 or more). Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the study site, over a 52 week treatment period. The study also includes a post-treatment follow-up period of 12 weeks. Study participation transportation, expenses and time will be facilitated or reimbursed.

Eligible patients: Individuals 40 – 80 years of age, with smoking history of >10 pack-years diagnosed with COPD emphysema/chronic bronchitis who are taking multiple daily inhalers and have a history of documented flare-ups (upper respiratory infections, COPD exacerbations or chest cold episodes) over past year.

ENHANCE 2: A Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD
Sponsor: Verona Pharma

The purpose of this study is to determine if ensifentrine is safe and effective for the treatment of patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).  Enrolled individuals with undergo 24-week long study in which nebulized study drug or placebo (1:1 ratio) will be administered twice daily. Participation and all related costs will be reimbursed.

Eligibility: Individuals 40 – 80 years of age with smoking history of >10 pack-years, diagnosed with COPD/emphysema/chronic bronchitis or who are suspected to have COPD.

Evaluation of the Efficacy and Safety of VX-864 in Subjects With the PiZZ Genotype
Sponsor: Vertex pharmaceuticals

This study will evaluate the efficacy, safety and pharmacokinetics (PK) of VX-864, an oral medication, in PiZZ phenotype Alpha 1-Antitrypsin Deficiency subjects.

RETHINC: REdefining THerapy In Early COPD for the Pulmonary Trials Cooperative (RETHINC)
Sponsor: National Heart, Lung and Blood institute (NHLBI) or National Health Institute (NIH)

The first choice for therapy in persons with Chronic Obstructive Pulmonary Disease (COPD) is a long-acting bronchodilator. These persons have evidence of airflow obstruction on a special breathing test called “spirometry”.  However, it has been unclear whether current and former smokers who have symptoms but do not have evidence of airflow obstruction on spirometry benefit from bronchodilators.  Our aim is to determine whether such individuals will derive benefit from the use of bronchodilator therapy. In the study, patients will be randomized to receive an inhaler with either medication that is used to open up the airways of the lung, or placebo. After enrolling, breathing function and symptoms will be tracked over a period of several weeks.

PHASE 3/4 GLASSIA SAFETY, IMMUNOGENICITY, AND BRONCHOALVEOLAR LAVAGE STUDY
Sponsor: Glassia

This study for patients with certain types of alpha-1 anti-trypsin deficiency evaluates the body’s response to an IV alpha-1 replacement medication (called “Glassia”). In this study, eligible participants will receive infusions of the Glassia medication and various tests will be done to assess the body’s response to the medication, including blood work, and sampling of the fluid inside the lungs using a technique called “bronchoscopy”, in which a flexible camera is introduced into the lung to wash and sample the lung environment.

INtervention Study In overweightGHT Patients With COPD (INSIGHT COPD)
Sponsor: National Heart, Lung and Blood institute (NHLBI) or National Health Institute (NIH)

Symptoms of chronic obstructive pulmonary disease (COPD) and high body mass index (BMI) overlap. The investigators are trying to find out if a program proven to help people lose a modest amount of weight and increase their physical activity will improve COPD symptoms for those with a high BMI. The program uses a series of digital video discs (DVD) sessions focused on healthy eating and physical activity, and encourages participants to monitor their weight, diet, and physical activity for two years. For those who want to, they will be able to work with a health coach to help meet weight and activity goals. We hope that the program will lead to weight loss, better exercise tolerance, and less shortness of breath. To be in the study, participants will need to have COPD, high BMI, history of smoking, shortness of breath, and be at least 40 years old.

Sub-populations and intermediate outcomes in COPD study (SPIROMICS) – National Clinical Trial ID # 01969344
Sponsor: National Heart, Lung and Blood institute (NHLBI) or National Health Institute (NIH)

SPIROMICS I and SPIROMICS II are observational studies of Chronic Obstructive Pulmonary Disease (COPD). SPIROMICS I had two main aims: (1) To find groups of patients with COPD who share certain characteristics; (2) To find new ways of measuring whether or not COPD is getting worse and so provide new ways of testing whether a new treatment is working. SPIROMICS II has three primary aims. Aim 1 is to define the natural history of "Smokers with symptoms despite preserved spirometry" and characterize the airway mucus abnormalities underlying this condition. Aim 2 is to determine the radiographic precursor lesion(s) for emphysema, and identify the molecular phenotypes underlying airway disease and emphysema. Aim 3 is to advance understanding of the biology of COPD exacerbations through analysis of predisposing baseline phenotypes, exacerbation triggers and host inflammatory response.

Prospective Study to Validate Biomarkers of Seven Proposed Phenotypes in Clinically Stable Chronic Obstructive Pulmonary Disease and Comparison with Subjects Experiencing Exacerbations
Sponsor: AMGEN

COPD is recognized to be a classic example of gene-environment interaction resulting in markedly heterogeneous disease with many different phenotypes (or outward clinical manifestations of the disease). Defining homogenous subpopulations with specific COPD phenotypes will better characterize COPD in its multiple manifestations. The definition of these phenotypes links different laboratory and other tests to clinically meaningful patient characteristics that will lend themselves to specialized treatment approaches.

ASPIRE: Clinical Evaluation of Asthma Sensing Predictive Intuitive Respiratory E-alert Monitor (ASPIRE) in individuals undergoing bronchoprovocation testing
Sponsor: National Heart, Lung and Blood institute (NHLBI) or National Health Institute (NIH) in collaboration with the University of Irvine

Evaluate whether capturing early obstruction can be predicted by ASPIRE device, which is harmless, band-aid like temporary attachment to the abdomen during the bronchoprovocation test. Early obstruction may manifest by altered respiratory motion which may be captured by this devices. A small study stipend will be offered.

Eligibility: Individuals undergoing evaluation for asthma or airway disease who will undergo bronchoprovocation testing (Methacholine challenge test) in Pulmonary Function Lab at UCLA.

A 12-week Study Treating Participants Who Have alpha1-antitrypsin-related COPD With Alvelestat (MPH966) or Placebo. (ASTRAEUS)
Sponsor: Mereo

The purpose of this study is to investigate the effect of alvelestat (an oral neutrophil elastase inhibitor) on blood and sputum biomarkers in patients with Pizz or null genotype alpha-1 anti-trypsin deficient lung disease. Change in a number of different blood and sputum biomarkers related to lung damage, inflammation and elastase activity will be measured over a 12-week period. The effect on lung function and respiratory symptoms will also be measured. Enrolled subjects will take study drug or placebo twice daily for 12 weeks. Participation and all related costs will be reimbursed.

Eligibility: individuals 18-75 year of age diagnosed with Alpha-1 AT deficiency with PiZZ genotype with CT evidence of emphysema (we will perform chest CT if no study available).

Safety, Tolerability and Effect on Liver Histologic Parameters of ARO-AAT (SEQUOIA)
Sponsor: Arrowhead

The purpose of AROAAT2001 (SEQUOIA) is to evaluate the safety, tolerability and effect on liver histologic parameters with administration of the investigational product, ARO-AAT, in participants with alpha-1 antitrypsin deficiency (AATD). Participants will receive multiple subcutaneous doses of ARO-AAT over a period of up to 2 years Participation and all related costs will be reimbursed.

Eligibility: individuals 18-75 year of age diagnosed with Alpha-1 AT deficiency with PiZZ genotype with suspected liver or liver/lung abnormalities

Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency (ATALANTa)
Sponsor: National Institutes of Health (NIH), Mereo BioPharma

This is a Phase 2, multicenter, double-blind, randomized (1:1), placebo-controlled, 12-week, proof-of-concept study to evaluate the safety and tolerability as well as the mechanistic effect of oral administration of alvelestat (MPH966) as a pill, twice daily in subjects with confirmed AATD defined as Pi*ZZ, Pi*SZ, Pi*null, or another rare phenotype/genotype known to be associated with either low (serum AAT level <11 μM or <57.2 mg/dL) or functionally impaired AAT including "F" or "I" mutations.

Eligibility: Age ≥18 and ≤80 years;  Patients with a confirmed diagnosis of AATD: Pi*ZZ, Pi*SZ, Pi*null, or another rare phenotype/genotype known to be associated with either low (serum AAT level <11 μM or <57.2 mg/dL) or functionally impaired AAT including "F" or "I" mutations.