IMPALA

24 evidence topics · 4 sources

Objective

Pulmonary gas-transfer objective

“improve the transfer of oxygen from the lungs to the blood” (opens the source at this quote in a new tab)

Location and study date

Geographic participation

Attribute	Reported value
Clinical sites	“34”
Countries	“18”

Trial period reported in the plain language summary

Milestone	Reported date
Trial start	“February 2016”
Trial finish	“September 2019”

Study design

Phase 2/3 randomized trial

“IMPALA was a phase 2/phase 3, placebo-controlled, randomized, double-blind trial.” (opens the source at this quote in a new tab)

Blinded intervention period

“24-week, double-blind, placebo-controlled intervention period” (opens the source at this quote in a new tab)

Allocation and extension duration

Component	Reported value
Randomization ratio across continuous molgramostim, intermittent molgramostim, and placebo	“1:1:1”
Maximum open-label extension duration	“48 weeks”

Eligibility criteria

Adult autoimmune PAP population with impaired oxygenation

Eligibility component	Quoted criterion
Minimum age, years	“18”
Minimum alveolar-arterial oxygen difference, mm Hg	“25”
Resting arterial oxygen threshold, mm Hg	“75”

Treatment

Continuous and intermittent inhaled regimens

Treatment component	Quoted specification
Molgramostim dose	“300 μg/day”
Continuous regimen	“every week”
Intermittent regimen	“every other week”
Placebo during intermittent off-treatment weeks	“placebo”

Study outcomes

Rationale for using Alveolar-Arterial oxygen difference as the primary endpoint

Endpoint-selection rationale

“based on investigator recommendations and extensive use in prior studies.” (opens the source at this quote in a new tab)

Primary assessment time point

Measure	Assessment week
Change from baseline in alveolar-arterial oxygen difference	“24”

Statistical analysis description

Number of participants (Planned and analyzed)

Randomized participants

“138 with aPAP were randomized” (opens the source at this quote in a new tab)

Treatment-group allocation

Group	Randomized participants
Continuous molgramostim	“46”
Intermittent molgramostim	“45”
Placebo	“47”

Description of analysis sets

Summary

The published analysis distinguishes the original full analysis set from a revised analysis that replaced invalid oxygen-gradient measurements obtained during supplemental oxygen administration. Four participants were affected: one in each molgramostim group and two in the placebo group. The revised analysis used imputation. The original full-analysis-set primary comparison was not statistically significant.

Invalid arterial blood-gas measurements requiring revision

Affected group	Participants
Continuous molgramostim	“1”
Intermittent molgramostim	“1”
Placebo	“2”

Analysis populations reported in the initial congress presentation

Original analysis	Revised analysis
“A-aDO2* – FAS”	“A-aDO2* – Revised”

Results

Participant disposition

Completion of the blinded intervention

Group	Participants completing the blinded intervention
Continuous molgramostim	“97.8%”
Intermittent molgramostim	“97.8%”
Placebo	“93.6%”

Open-label extension enrollment

Disposition measure	Participants
Enrolled in the open-label extension	“131”

Baseline characteristics

Demographic and pulmonary-function characteristics

Characteristic	Continuous molgramostim	Intermittent molgramostim	Placebo
Age, years, mean and standard deviation	“54.0±13.3”	“49.2±14.1”	“46.1±14.8”
DLCO percent predicted, mean and standard deviation	“51.9±18.5”	“46.1±14.5”	“49.6±14.3”
Alveolar-arterial oxygen difference, mm Hg, mean and standard deviation	“40.5±19.6”	“40.9±20.2”	“40.2±14.3”

Efficacy results

Initial congress report: original and revised primary analyses

“Endpoint”	“Units”	“Treatment effect”	“P-value”
“A-aDO2* – FAS”	“mm Hg”	“-4.6”	“0.1688”
“A-aDO2* – Revised”	“mm Hg”	“-6.5”	“0.0249”

Published primary analysis: continuous molgramostim versus placebo

Analysis	Estimated treatment difference in alveolar-arterial oxygen difference, mm Hg	P-value
Original full analysis set	“−5.2”	“P=0.118”
Revised analysis with invalid measurements replaced by imputation	“−6.2”	“P=0.025”

Published secondary pulmonary and exercise outcomes at week 24

Outcome	Estimated treatment difference and 95% confidence interval
DLCO percent predicted, percentage points	“7.8 (2.3 to 13.3)”
Ground-glass opacity score	“−2.5 (−3.7 to −1.2)”
Six-minute walk distance, m	“24.6 (−15.3 to 64.4)”

Health-related quality of life and patient-reported outcomes

SGRQ Total Score at week 24

Outcome	Estimated treatment difference and 95% confidence interval
Continuous molgramostim versus placebo, SGRQ Total Score	“−7.4 (−13.1 to −1.6)”

Safety results

Mortality during the study

“No deaths occurred during the study.” (opens the source at this quote in a new tab)

Study limitations

Summary

The primary result depends on the analysis used. The original full-analysis-set comparison was not statistically significant; the revised analysis replaced invalid measurements from four participants and yielded a statistically significant difference. The earlier congress presentation and the subsequently published analysis report different numerical estimates and should remain separate evidence items.

Blinded treatment lasted 24 weeks. The six-minute walk-distance confidence interval included no difference, and the subsequent extension did not retain a placebo control. These findings do not establish effects on mortality or long-term comparative safety.