Evaluation of the Efficacy and Safety of MV130 in Chronic Obstructive Pulmonary Disease (COPD)

Phase 2

Completed

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Interventions: Biological: MV130
Biological: Placebo

Registration Number: NCT01842360

Lead Sponsor: Inmunotek S.L.

Brief Summary: The goal of this clinical trial is to learn whether the bacterial vaccine MV130 helps reduce the number of exacerbations in adults with moderate to severe COPD. It will also assess the safety and immune effects of MV130. The main questions it aims to answer is: Does MV130 lower the number and severity of COPD flare-ups? Other questions include: Does it reduce the use of healthcare resources and improve quality of life?

Researchers will compare MV130 to a placebo (a similar spray without the active substance; bacterial species) to see how well it works. Participants will use either MV130 or placebo daily under the tongue for 12 months, attend regular clinic visits, and be followed for an additional 6 months to monitor health outcomes and side effects.

Detailed Description: This was a randomized, double-blind, placebo-controlled, prospective, parallel, multicenter clinical trial designed to evaluate the efficacy, safety, and immunomodulatory effects of a sublingually administered bacterial polyvalent vaccine (BACTEK®, also known as MV130) in adult participants with moderate to severe Chronic Obstructive Pulmonary Disease (COPD). The study was conducted by Inmunotek, S.L., and included seven sHospitals across Spain. A total of 198 participants were enrolled and randomized equally into two groups to receive either MV130 or placebo over a period of 12 months, followed by a 6-month observation phase, totaling 18 months of participation per participant.

The investigational product, MV130, consisted of a glycerinated suspension containing six inactivated non-lysate bacterial species: Streptococcus pneumoniae, Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. The product was administered sublingually at a dosage of two sprays (0.2 mL total) per day. The placebo formulation was identical in appearance and composition, excluding the active bacterial components. All study participants received their first dose under supervision at the clinical site and were trained for home administration.

Eligible participants were between 35 and 85 years old, with a diagnosis of moderate or severe COPD according to GOLD guidelines, a history of recurrent exacerbations (≥3 moderate or ≥2 with at least one hospitalization in the past year), and a smoking history of at least 10 pack-years. Subjects were excluded if they had very severe COPD, a history of recent exacerbations or systemic corticosteroid use, concurrent immunodeficiency or serious comorbid conditions, or if they were pregnant, breastfeeding, or unwilling to use contraception during the study.

The primary efficacy endpoint was the total number of COPD exacerbations during the full 18-month period. Secondary endpoints included the severity of exacerbations, time to first exacerbation, healthcare resource usage (hospitalizations, emergency room visits, unscheduled consultations), medication use, health-related quality of life (assessed using the CAT questionnaire), and a pharmacoeconomic evaluation based on healthcare expenditures. In a subset of participants, immunological parameters were also assessed to explore the immunomodulatory response. Safety analysis included all randomized participants.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 198

Inclusion Criteria

Written informed consent.
Both sexes.
Age between 35 and 85.
Must be capable of complying with the dosing regimen.
Diagnosis of moderate or severe COPD according to GOLD criteria.
Experienced at least three moderate exacerbations (i.e., those requiring treatment with antibiotics, systemic corticosteroids, or both, as prescribed by their general practitioner or pulmonologist in the standard consultation and/or the Emergency Department of their Clinic) or two exacerbations with at least one requiring hospitalization due to a COPD exacerbation and the other one a moderate exacerbation occurred within the last year.
Not changed their medication for the maintenance treatment of COPD within the past 6 months.
Consumption of 10 or more packs of cigarettes/year. Participants may be or not active smokers.
Live in the Autonomous Community of Madrid throughout the study period.
Women of childbearing age women of must use an approved contraceptive method and obtain a negative result in the urine pregnancy test performed during the screening visit.

Exclusion Criteria

Participants outside allowed age range.
Participants unable to cooperate and/or have a severe psychiatric disorder.
Women who are pregnant, breastfeeding, expect to become pregnant during the study (including assisted reproduction), or who refuse to use contraceptives during the study (including barrier methods). Women who become pregnant during the clinical trial will have to discontinue their participation in it.
Participants who has participated in a study or clinical trial with an investigational product in the last 3 months before inclusion.
Participants diagnosed with asthma based on the guidelines of the American Thoracic Society and the European Respiratory Society. If the investigators are unable to differentiate between COPD and asthma after applying the criteria listed in the following table, a bronchodilator test with inhaled salbutamol must be performed, excluding those subjects with FEV1 changes >400 ml.
Participants with a diagnosis other than COPD that causes them to have an unstable condition or a life expectancy <3 years.
Participants who had an exacerbation within 4 weeks before starting the trial.
Participants with moderate COPD who required treatment with inhaled corticosteroids in the last 4 weeks.
Participants with moderate COPD who received systemic corticosteroids (orally, intramuscularly, or intravenously) in the last 4 weeks.
Participants diagnosed with a Primary or Secondary Immunodeficiency within the 12 months preceding their inclusion in the clinical trial or the trial's baseline visit.
Participants diagnosed with chronic lymphoproliferative disease.
Participants diagnosed with chronic infectious disease.
Participants with chronic heart disease, arrhythmias, or episodes of arrhythmia secondary to the administration of bronchodilators.
Participants diagnosed with COPD and chronic colonization by Pseudomonas aeruginosa.
Participants with COPD and bronchiectasis diagnosed by CT imaging before the age of 40.
Participants diagnosed with very severe COPD according to the GOLD classification.
Participants requiring home oxygen therapy or non-invasive mechanical ventilation.
Participants with a history of hypersensitivity to any of the vaccine's components.
Participants receiving immunosuppressive treatment with: azathioprine, methotrexate, ciclosporin, cyclophosphamide, tacrolimus, antimalarial drugs, or gold salts.
Participants who have been treated with monoclonal antibodies such as rituximab or TNF-alpha inhibitors in the last 6 months.
Participants receiving chronic treatment with azithromycin or inhaled antibiotics (tobramycin or colistin).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active - MV130	MV130	The participants will receive daily dose of MV130 during 12 months sublingually.
Placebo	Placebo	The participants will receive daily dose of placebo during 12 months sublingually.

Primary Outcome Measures

Name	Time	Method
Number of COPD Exacerbations.	18 months	Comparison in the number of COPD exacerbations in the two study groups in the 18-month study period.

Secondary Outcome Measures

Name	Time	Method
Change in the Rate of COPD Exacerbations.	18 months	Incidence is the number of new events per total participants in the sample population.
Time Elapsed Between Start of Treatment and First COPD Exacerbation.	18 months	For reference, median survival or event-free times are reported with the 95% CI of the median.
Change in Severity of COPD Exacerbations.	18 months	The severity of exacerbations was to be measured by the consumption of health care resources: Emergency Department/Hospitalisation/Intensive Care Unit/Consultations visits, as follows: ICU hospitalisation 4 points Hospitalisation 3 points Emergency room visit 2 points Consultation resulting in change in usual treatment 1 point
Use of Drugs (Antibiotics, Corticosteroids, Etc).	18 months	The use of drugs will be calculated using the following index: * antibiotics: 1 point * inhaled corticosteroids: 2 points * systemic corticosteroids: 3 points
Number of Hospitalizations Due to a COPD Exacerbation.	18 months	The same patient could have more than one hospitalizations.
Number of Visits to the Emergency Room.	18 months	Number of individual visits were recorded per patient. One patient could have multiple visits.
Days of Hospitalization Due to a COPD Exacerbation.	18 months	Number of days of hospitalization per patient were recorded. The same patient could have more than one hospitalization.
Number of Unscheduled Medical Consultations Due to COPD	18 months.	Number of consultations per patient. One patient could have multiple consultations.
Health Related Quality of Life.	18 months	COPD Assessment Test per patient determined by an adapted version of the specific COPD Assessment Test. Minimum value is 0 (better) and maximum value is 40 (worse). The change between two or more time points is reported. Change between baseline and 18 months in shown.
Healthcare Resource Utilization During COPD Exacerbations	18 months	Healthcare resource utilization was assessed as the sum of: * Complementary tests * Programmed visits to the specialist * Total number of visits to the specialist * Non-programmed visits to the specialist * ICU hospitalization days * Visits to the emergency room * Days hospitalized * Sum of antibiotics * Number of visits to General Practitioner * Sum of oral corticosteroids * Number of telephone calls to the GP * Sum of inhalers * Home visits * Sum of antipyretics Total number of healthcare resources used during COPD exacerbation episodes. Data were summarized per treatment group and reported as total counts and percent differences. No baseline or monetary data were collected
Adverse Events and Overall Tolerability (Adverse Reactions).	18 months	Total number of adverse events in Active (MV130) and Placebo groups were compared.

Trial Locations

Locations (7): Hospital Universitario de Torrejón
🇪🇸
Torrejón de Ardoz, Madrid, Spain
Hospital Universitario de Vic
🇪🇸
Vic, Barcelona, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸
Madrid, Spain
Hospital Universitario Infanta Leonor
🇪🇸
Madrid, Spain
Hospital Clínico San Carlos
🇪🇸
Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Hospital Universitario La Paz
🇪🇸
Madrid, Spain
Hospital Universitario de Torrejón
🇪🇸Torrejón de Ardoz, Madrid, Spain