Weekly IV human alpha1‑proteinase inhibitor at multiple doses for safety and effectiveness in adults with alpha1 antitrypsin deficiency‑related emphysema

The primary objective is to assess whether two investigational dose levels of Respreeza/Zemaira modify the annual lung density decline rate measured by computed tomography in adults with alpha1 antitrypsin deficiency–related emphysema, compared with the approved dosing regimen; this surrogate endpoint is clinically relevant as it reflects the rate of disease progression and potential preservation of lung function. Safety and tolerability of the administered doses are also evaluated throughout the three‑year treatment period.

The trial enrolled adult participants aged 18–65 years, inclusive of both sexes. All participants had a confirmed diagnosis of emphysema associated with Alpha1 antitrypsin deficiency, with PiZZ, PiZ(null) or Pi(null/null) genotype and documented serum AAT levels below 11 µM (<50 mg/dL). The population comprised patients classified as vulnerable, reflecting inclusion of individuals who may be at increased risk due to disease severity. No specific dietary, physical activity, or habit restrictions were stipulated in the available description. The sponsor did not provide the total number of participants.

The study is a Phase 4, multicenter, double‑blind, randomized, controlled trial evaluating three weekly intravenous dose levels of Respreeza (human alpha1‑proteinase inhibitor) administered over a 3‑year maintenance period in adults with alpha1 antitrypsin deficiency–related emphysema. After an initial screening visit to confirm genotype, serum AAT level, and eligibility criteria, participants undergo a baseline visit that includes pulmonary function testing, CT lung density assessment, and safety laboratory collection before the first infusion. Weekly infusion visits continue throughout the 3‑year treatment phase, with scheduled follow‑up visits (e.g., quarterly) for CT density measurements, spirometry, diffusion capacity, and adverse‑event monitoring. The end‑of‑study visit occurs at the conclusion of the 3‑year period and includes final efficacy and safety evaluations. Participant involvement therefore spans approximately 3 years plus the screening period. Early termination may occur due to serious adverse events, inability to tolerate infusions, non‑compliance with the protocol, withdrawal of consent, or loss to follow‑up.

The investigational products are Respreeza 4,000 mg powder and solvent for solution for infusion and Respreeza 1,000 mg powder and solvent for solution for infusion. Both are supplied as a solution for infusion containing human alpha1‑proteinase inhibitor and are administered by intravenous infusion. Each dose corresponds to the amount indicated in the product name (4,000 mg or 1,000 mg) and is given once weekly for a duration of up to three years.

The study also includes a comparator arm receiving the marketed dose of Respreeza (Zemaira) administered weekly by intravenous infusion. This dose reflects the standard maintenance regimen for adults with emphysema related to alpha1 antitrypsin deficiency.

All infusions are performed in a clinical setting under controlled conditions. Dosing schedules are recorded in an electronic infusion log, and participant compliance is monitored through regular review of infusion records and periodic measurement of serum alpha1‑proteinase inhibitor levels. Adverse events and tolerability are assessed throughout the treatment period.

The primary efficacy assessment is the annual rate of change in adjusted lung density, evaluated by comparing longitudinal measurements obtained throughout the study period to determine the decline in lung tissue density over time.

Secondary efficacy assessments include the annual rate of change in forced expiratory volume in 1 second percent predicted (FEV1%), the annual rate of change in diffusion capacity of carbon monoxide (DLco), the number of severe pulmonary exacerbations, and the duration of severe pulmonary exacerbations. Additional secondary endpoints encompass the number of participants experiencing treatment‑emergent adverse events (TEAEs) and the percentage of participants experiencing TEAEs. These parameters will be measured at predefined intervals over the three‑year treatment period to allow calculation of annual rates and event frequencies.