Clinical evidence
3.1.1IMPALA-2
36 evidence topics · 15 sources
Evaluation of efficacy and safety
3.1.1.2Location and study date
Geographic participation and open-label data cutoff
Randomized double-blind trial
Randomization and treatment-period durations
3.1.1.4Eligibility criteria
Autoantibody confirmation and impaired pulmonary gas transfer
Stability of pulmonary gas transfer during screening
Investigational molgramostim dose
Randomized treatment and open-label crossover
3.1.1.6.1Rationale for using hemoglobin-adjusted DLCO percent predicted as the primary endpoint
Primary endpoint definition
Clinical rationale for measuring pulmonary gas transfer
Historical limitations of outcome-measure validation
Subsequent post-hoc correlations with respiratory quality of life
Planned health economics and quality-of-life assessments
3.1.1.7Statistical analysis description
3.1.1.7.1Number of participants (Planned and analyzed)
Planned sample size and statistical power
3.1.1.7.2Description of analysis sets
Summary
The primary efficacy population includes all randomized participants, analyzed by assigned treatment. Safety analyses use participants who received at least one dose, analyzed by treatment received. The plan specifies a mixed model for repeated measures and control-based imputation for missing efficacy data. Safety analyses do not impute missing data. Multiplicity procedures differ between Japan and South Korea and the other participating regions; a nominal P-value below 0.05 therefore does not independently establish significance for every secondary endpoint.
Analysis populations and statistical methods
Procedures for handling missing data
3.1.1.8.1Participant disposition
Double-blind treatment completion
Entry into and withdrawal from the open-label period
3.1.1.8.2Baseline characteristics
Demographic and pulmonary-function characteristics
3.1.1.8.3Efficacy results
Primary endpoint: pulmonary gas transfer at week 24
Pulmonary gas transfer at week 48
Number of participants with at least one whole lung lavage procedure over 48 weeks
Exploratory treadmill exercise capacity: distance walked
Post-hoc biomarker analyses
Open-label pulmonary gas transfer through week 96
3.1.1.8.4Health-related quality of life and patient-reported outcomes
SGRQ Total Score: randomized treatment-period changes
SGRQ secondary endpoints and multiplicity
Inferential limitation after the SGRQ Activity comparison
Open-label SGRQ Total Score through week 96
EQ-5D-5L descriptive system: exploratory results
Double-blind treatment-period safety
Open-label treatment-period adverse events
Summary
The randomized comparison involved 164 participants and 48 weeks of blinded treatment. The primary endpoint measures pulmonary gas transfer rather than survival or hospitalization. Post-hoc correlations with SGRQ support clinical relevance but do not establish that DLCO is a validated surrogate for every patient-important outcome. The SGRQ Activity comparison did not meet the prespecified multiplicity requirements, and subsequent secondary or exploratory results should not be treated as independent confirmatory findings.
The week-96 extension results are uncontrolled because both groups received molgramostim after week 48. The extension reports arithmetic mean changes rather than the adjusted randomized-treatment estimates. Its three reported deaths were assessed as unrelated to treatment; the earlier statement that no deaths occurred applies to the double-blind report, not to all subsequent follow-up.