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

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.

If interested, please email at: [email protected]

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.

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. 

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.

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.

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.

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.

Evaluate Efficacy and Safety of "Kamada-AAT for Inhalation" in Patients With AATD (InnovAATe) (Not enrolling yet!)
Sponsor: Kamada

Alpha-antitrypsin (AAT) is a member of the serpin family of proteinase inhibitors and is to a large extent responsible for restricting proteinases, notably neutrophil elastase, and proteinase 3, which might otherwise attack the lung tissue. Individuals with a genetic deficiency of alpha-1-antitrypsin (AATD) are at a significantly increased risk (80-100%) of developing emphysema. This study is designed to administer a solution of AAT by nebulizer so that patients can inhale the drug instead of requiring infusions as in current treatment. A significant advantage of inhalation is that the AAT is directly transferred to the lungs, which is the site most in need of the protein. Previous results show that in addition to the added convenience, three times higher concentrations of AAT can be achieved in the lungs by inhalation than by intravenous infusions. To date, more than 220 patients have completed Inhalation studies for several indications.

The current study population will consist of adult patients with congenital alpha-1 antitrypsin (AAT) deficiency who have moderate airflow limitation (forced expiratory volume in 1 second 50% ≤ [FEV1] ≤ 80% of predicted) and FEV1/slow vital capacity [SVC] ≤ 70% and who have not experienced two or more moderate or one or more severe exacerbations of COPD during the past year. A total of 220 patients will be recruited, and after 4 weeks practice inhaling saline with the nebulizer, will be randomized 1:1 to inhale either 80 mg/day "Kamada-AAT for Inhalation" or a placebo with identical appearance. Patients will be treated for 104 weeks and then followed up for a further 26 weeks. Over this time there will be 13 visits to the clinical study site for evaluation of lung function by blood tests and CT densitometry. In addition the patients will be required to fill out a daily e-diary with details of the inhalations and will also report their daily symptoms.

Ongoing Studies No Longer Enrolling

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.