A Phase 2 interventional study of alpha1-proteinase inhibitor, produced from the plasma of human donors (Prolastin 1000 mg, powder and solvent for solution for infusion) and Placebo in Acute Exacerbation Chronic Obstructive Pulmonary Disease, sponsored by Fondazione IRCCS Policlinico San Matteo di Pavia. Not yet recruiting at 1 site in Italy. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2025-08-24.
Sponsored by Fondazione IRCCS Policlinico San Matteo di Pavia · Phase 2, Interventional, and Treatment
Intravenous augmentation therapy with purified preparations of AAT (Alpha1-antitrypsin) derived from human plasma is a well consolidated specific therapeutic option to treat the severe deficient state of AAT. Prolastin is used to restore the balance between AAT and elastases in the lung and consequently to prevent a further deterioration in the pulmonary emphysema. Recently, in patients with COVID-19, without genetically lowered AAT levels with moderate to severe ARDS, treatment with AAT was demonstrated to be safe, feasible, and biochemically efficacious as an anti-inflammatory therapeutic therapy.
The aim of the study, based on biological plausibility, is to evaluate the safety and efficacy (from a biological perspective) of the administration of intravenous plasma-purified AAT as an anti-inflammatory treatment for patients admitted to hospital because of a COPD exacerbation leading to an acute or an acute on chronic respiratory failure.
Thirty-six adult patients hospitalized because of a COPD exacerbation leading to an acute or an acute on chronic respiratory failure will be enrolled by the two sites involved in the study, the Pneumology Unit of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) and the Pneumology Unit of IRCCS Istituto Clinico Humanitas, Rozzano (Milano, Italy).
Participants will be randomized 2:1 in the active treatment group (standard treatment + IV administration of Prolastin) or in the placebo group (standard treatment+ IV administration of 0.9% sodium chloride).
To address the clinical question from a biological perspective, we will investigate the decrease in inflammatory markers in the active treated group in comparison with the placebo group.
The primary objective is to demonstrate a significant reduction in systemic inflammation by IV Prolastin administered once at 120 mg per kilogram of body weight in patients with moderate to severe AECOPD, as assessed by the change in plasma concentration of IL6 at 7 days after randomization, in the active treatment group with respect to placebo group.
Secondary outcomes are:
The expected duration of subject participation is from randomization to 30 days after hospital discharge, with a follow up phone contact.
COPD is the third leading cause of death in the world and it is characterized by airflow limitation, breathlessness, and exacerbations. Exacerbations are important events with a significant influence on prognosis and survival. Neutrophils, eosinophils, other inflammatory cells in the lung, as well as systemic inflammation and inflammatory biomarkers increase during exacerbations. Alpha1-antitrypsin (AAT) is an acute phase protein with antineutrophil elastase properties and several studies have demonstrated an elevation of acute phase proteins during COPD exacerbations. Intravenous augmentation therapy with purified preparations of AAT, derived from human plasma, is a well consolidated specific therapeutic option to treat the severe deficient state of AAT. In turn, the abrupt cessation of AAT augmentation therapy for patients with a hereditary deficiency of the protein results in increased systemic inflammation and subsequent progression of emphysema and COPD. Recently, in patients with COVID-19, without genetically lowered AAT levels with moderate to severe ARDS (Acute Respiratory Distress Syndrome), treatment with AAT was demonstrated to be safe, feasible, and biochemically efficacious as an anti-inflammatory therapy. This suggests a potential protective effect of AAT in treating COPD exacerbations in subjects without the genetic deficiency of AAT because of the anti-inflammatory effect of AAT.
Primary objective:
- to demonstrate a significant reduction in systemic inflammation by IV Prolastin administered once at 120 mg per kilogram of body weight in patients with moderate to severe AECOPD, as assessed by the change in plasma concentration of IL6 at 7 days after randomization, in the active treatment group with respect to placebo group.
Secondary objectives:
to identify treatment failure as assessed by:
to determine the safety of IV Prolastin administered once at 120 mg per kilogram of body weight, as assessed by the type and number of AEs and SAEs in the two groups.
Primary study outcome:
Secondary study outcomes:
Recruitment will take place at the Pneumology Unit of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) and at the Pneumology Unit of IRCCS Istituto Clinico Humanitas, Rozzano (Milano, Italy), during the hospitalization because of a COPD exacerbation leading to an acute or an acute on chronic respiratory failure.
At the Screening day, the following data will be collected: demographics (date of birth, sex, ethnicity), medical history and medications (previous and concomitant, including those administered at emergency room access), vital signs (systolic/diastolic blood pressure, heart rate, peripheral oxygen saturation, respiratory rate), electrocardiogram. The following screening assessments will be undertaken to ensure that a patient meets the criteria for enrolment:
At the Baseline day (if different from the screening day), a physical examination will be performed and vital signs will be collected again. Before randomization, the following laboratory assessments will be carried out as per routine clinical care (blood count, basic liver/renal/bone profile biochemistry, standard markers of inflammation such as C-reactive protein, arterial blood gas analysis). A plasma sample will be obtained for cytokine measurements (IL-6, IL-1b, IL-5, IL-8, IL-10, sTNFR1), for AAT antielastase activity, active elastase ad serum AAT level before randomization. Within 24 hours by the admission to the respiratory ward, subjects who meet inclusion criteria will be randomized 2:1 to one of the two study arms (Prolastin or placebo), according to a computer-generated random blocks randomization list. Both the active drug and matching placebo will be prepared by unblinded trial personnel.
At the Baseline day the investigational product (Prolastin or placebo) will be administered, concomitant medications will be collected and the adverse events evaluation will be performed.
At Day 7 (seven day after IMP administration) the following assessments will be performed:
At the Hospital Discharge Day, the following data will be collected:
A Phone contact, 30 days after discharge, will be done to record:
Fondazione IRCCS Policlinico San Matteo di Pavia is the lead sponsor of 255 studies on the registry; 113 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that, in the opinion of the Investigator, could:
Alpha1-proteinase inhibitor (human), commercially available as Prolastin
Biological: alpha1-proteinase inhibitor, produced from the plasma of human donors (Prolastin 1000 mg, powder and solvent for solution for infusion)
0.9% sodium chloride solution for infusion ("normal saline")
Drug: Placebo
IV Prolastin administered once at 120 mg per kilogram of body weight
\+ IV administration of 0.9% sodium chloride
Change in level of circulating IL-6 in plasma
change in level of circulating IL-6 in plasma at 7 days after IMP administration, as measured by ELISA
Time frame: at 7 days after IMP administration
Change in plasma concentration of IL-1b, IL-5, IL-8, IL-10, and soluble TNF receptor 1(sTNFR1), CRP
change in plasma concentration of IL-1b, IL-5, IL-8, IL-10, and soluble TNF receptor 1(sTNFR1), CRP at 7 days after randomization
Time frame: at 7 days after after randomization
Differences in the AAT antielastase activity, the amount of active elastase, the AAT levels in serum
differences in the AAT antielastase activity, the amount of active elastase, the AAT levels in serum at baseline and at 7 days after randomization
Time frame: at baseline and at 7 days after randomization
Treatment failure
treatment failure (need for either NIV or CPAP or ETI or transfer to ICU or in-hospital death after randomization)
Time frame: from randomization to 30 days after hospital discharge
Impact of AECOPD on overall health, daily life, and perceived well-being
Impact of AECOPD on overall health, daily life, and perceived well-being in patients with obstructive airways disease by the change of St. George's Respiratory Questionnaire (SGRQ) score (scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status) from Day 7 to follow-up (30 days after hospital discharge)
Time frame: from Day 7 to 30 days after hospital discharge
Type and number of AEs and SAEs
Differences in type and number of AEs and SAEs in the two groups (active and placebo)
Time frame: from randomization to 30 days after hospital discharged
This study is not yet recruiting, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.
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Fondazione IRCCS Policlinico San Matteo di Pavia