GEMINI-1

20 evidence topics · 10 sources

Objective

Primary objective: treatment of GPP flares

“To evaluate the efficacy of imsidolimab compared with placebo” (opens the source at this quote in a new tab)

Location and study date

Geographic scope of the phase 3 program

“26 clinical sites within 11 countries” (opens the source at this quote in a new tab)

Registry dates

Milestone	Reported date
First participant enrollment	“14/04/2022”
Last data collection	“17/08/2023”

Study design

GEMINI-1: design and allocation

“a four week, double-blind, placebo-controlled, randomized study” (opens the source at this quote in a new tab)
“randomized 1:1:1” (opens the source at this quote in a new tab)

Eligibility criteria

GEMINI-1: flare eligibility criteria

“BSA affected with pustules [excluding palms and soles] of at least 5%” (opens the source at this quote in a new tab)
“GPPPGA score of at least 3” (opens the source at this quote in a new tab)
“PRS score of at least 3” (opens the source at this quote in a new tab)

Exclusion of immediately life-threatening flares

“Subject flare is so severe that patient's life is at risk” (opens the source at this quote in a new tab)

Treatment

GEMINI-1: randomized treatment

“750mg IV imsidolimab, 300mg IV imsidolimab or placebo” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using GPPPGA response as the primary endpoint

GPPGA and GPPASI validation

“the GPPGA and GPPASI are valid, reliable and responsive measures for the assessment of GPP disease severity” (opens the source at this quote in a new tab)

Prespecified primary and key secondary response thresholds

Endpoint	Response threshold
Primary: GPPPGA at week 4	“0 (clear) or 1 (almost clear)”
Key secondary: PRS at week 1	“0 (clear) or 1 (almost clear)”

Statistical analysis description

Number of participants (Planned and analyzed)

GEMINI-1: enrolled participants and treatment groups

“45 patients, 15 patients per arm” (opens the source at this quote in a new tab)

Planned sample size and marginal power assumptions

Parameter	Value
Total planned participants	“45”
Participants per group	“15”
Power for each marginal hypothesis test	“82%”
Assumed absolute difference in response proportions	“43.3%”

Description of analysis sets

Prespecified analysis populations

Analysis population	Definition excerpt
Intention-to-treat population	“all randomized subjects”
Safety population: exposure requirement for randomized participants	“receive 1 dose of imsidolimab or placebo”

Prespecified primary analysis and multiplicity sequence

Method	Protocol wording
Primary response comparison, stratified by baseline GPPPGA	“Cochran-Mantel-Haenszel (CMH) Chi-square test”
Sequence: 750-mg primary, 750-mg key secondary, 300-mg primary, 300-mg key secondary	“H1→ H3→ H2→ H4”
Missing primary endpoint scores after dropout	“Multiple Imputations”

Results

Participant disposition

Placebo participants requiring early crossover to imsidolimab

“66.7% (10/15)” (opens the source at this quote in a new tab)

Baseline characteristics

No evidence found.

Efficacy results

GEMINI-1: week 4 results

Endpoint	“300 mg”	“750 mg”	“placebo”
“GPPPGA scores of 0 or 1 at week 4”	“53%”“(n=8/15)”	“53%”“(n=8/15)”	“13%”“(n=2/15)”
P value	“P=0.023”	“P=0.023”

Earlier sponsor report: 750-mg primary endpoint comparison

“p=0.0131” (opens the source at this quote in a new tab)

Key secondary endpoint: PRS 0 or 1 at week 1

Randomized group	Response percentage
Imsidolimab 750 mg IV	“40.0”
Imsidolimab 300 mg IV	“66.7”
Placebo	“13.3”

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Serious and severe adverse events in imsidolimab-treated participants

“No SAEs or severe AEs reported in imsidolimab-treated patients” (opens the source at this quote in a new tab)

Anti-drug antibodies in imsidolimab-treated participants

Measure	Reported finding
Participants with detectable antibodies	“One of 30 (3.3%)”
Neutralizing activity	“non-neutralizing”

Study limitations

Summary

The trial included 45 participants, with 15 per group, and a four-week placebo-controlled period. Ten of 15 placebo participants required early crossover. These features limit precision and longer-term randomized comparisons. The protocol excluded flares considered immediately life-threatening, limiting direct applicability to that population. The prespecified testing sequence placed the 750-mg key secondary endpoint before the 300-mg primary endpoint; individual reported P values should not be interpreted as independent of that sequence.