Intravenous Alpha-1 Antitrypsin for Hospitalized Patients With COPD Exacerbations (AECOPD Study)

NCT07125664 · tracked via the Priya Life Science Italy tracker

Sponsor

Fondazione IRCCS Policlinico San Matteo di Pavia

Phase

Phase 2

Started

2025-10-01

Last updated

2025-08-24

Condition(s) studied

Acute Exacerbation Chronic Obstructive Pulmonary Disease

Investigational drug(s) / intervention(s)

alpha1-proteinase inhibitor, produced from the plasma of human donors (Prolastin 1000 mg, powder and solvent for solution for infusion)Placebo

alpha1-proteinase inhibitor, produced from the plasma of human donors (Prolastin 1000 mg, powder and solvent for solution for infusion): IV Prolastin administered once at 120 mg per kilogram of body weight

Placebo: \+ IV administration of 0.9% sodium chloride

Study summary

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:

1. Difference in 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.
2. Differences in AAT antielastase activity, the amount of active elastase, the AAT levels in serum at baseline and at 7 days after randomization.
3. Difference in treatment failure rate. Treatment failure is a composite endpoint of need for either NIV or CPAP or need of ETI or need of transfer to ICU or in-hospital death after randomization
4. 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 from Day 7 to follow-up (30 days after hospital discharge).
5. Differences in type and number of AEs and SAEs in the two groups

The expected duration of subject participation is from randomization to 30 days after hospital discharge, with a follow up phone contact.

Eligibility

Sex

ALL

Min age

40 Years

Max age

—

Healthy volunteers

Inclusion Criteria: 1. Informed Consent as documented by signature 2. Male and female ≥40 years old 3. Previous COPD diagnosis with a documented post-bronchodilator FEV1 to FVC ratio (FEV1/FVC) equal to or less than 0.70 or LLN 4. Hospitalized for a moderate to severe exacerbation, according to the Rome proposal 5. Admission to the respiratory ward by ≤24 hours 6. Acute respiratory failure with SpO2 \<92% at room air, or PaO2\< 60 mmHg at room air, or acute on chronic respiratory failure defined as higher Increased oxygen requirements compared with the home standard oxygen prescription 7. A positive sputum NEATstik®, that corresponds to an approximate neutrophil elastase concentration of 8 μg·mL-1 (rapid point-of-care test) Exclusion Criteria: 1. Clinically important pulmonary disease other than COPD (e.g., clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, and primary ciliary dyskinesia) 2. Presence of pneumonia or other pleuroparenchymal abnormalities on either chest X-ray or Chest CT scan, performed per routine clinical practice at the hospital admission 3. Current diagnosis of asthma according to the GINA, prior history of asthma, or asthma-COPD overlap 4. Known AATD as homozygous or composite heterozygous mutation 5. Presence of any active malignancy (other than non-melanoma skin cancer) 6. 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: 1. Affect the safety of the participant throughout the study 2. Influence the findings of the study or their interpretation 7. Known diagnosis of selective IgA deficiency defined as a serum IgA of less than 7 mg/dl (0.07 g/L) 8. Patient with the immediate need for ETI of NIV (patients already on CPAP or NIV can be included) 9. Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product 10. Women who are of childbearing potential\* 11. Participants that have previously received Prolastin® 1000 mg/40 ml 12. Participation in another interventional clinical trials with investigational drugs within the 30 days preceding and during the present study. \* A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the randomisation without an alternative medical cause.

Primary outcome measure(s)

Change in level of circulating IL-6 in plasma — at 7 days after IMP administration
change in level of circulating IL-6 in plasma at 7 days after IMP administration, as measured by ELISA

Trial sites (1)

Facility	City	Region	Status
Fondazione IRCCS Policlinico San Matteo	Pavia	Lombardy

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07125664 on ClinicalTrials.gov ↗ ← All trials in Italy