Section 4 of 6
Clinical evidence
111 evidence topics · 30 sources
Primary objective: treatment of GPP flares
3.1.1.2Location and study date
Geographic scope of the phase 3 program
GEMINI-1: design and allocation
3.1.1.4Eligibility criteria
GEMINI-1: flare eligibility criteria
Exclusion of immediately life-threatening flares
GEMINI-1: randomized treatment
3.1.1.6.1Rationale for using GPPPGA response as the primary endpoint
GPPGA and GPPASI validation
Prespecified primary and key secondary response thresholds
3.1.1.7Statistical analysis description
3.1.1.7.1Number of participants (Planned and analyzed)
GEMINI-1: enrolled participants and treatment groups
Planned sample size and marginal power assumptions
3.1.1.7.2Description of analysis sets
Prespecified analysis populations
Prespecified primary analysis and multiplicity sequence
3.1.1.8.1Participant disposition
Placebo participants requiring early crossover to imsidolimab
3.1.1.8.2Baseline characteristics
No evidence found.
3.1.1.8.3Efficacy results
Earlier sponsor report: 750-mg primary endpoint comparison
Key secondary endpoint: PRS 0 or 1 at week 1
3.1.1.8.4Health-related quality of life and patient-reported outcomes
No evidence found.
Serious and severe adverse events in imsidolimab-treated participants
Anti-drug antibodies in imsidolimab-treated participants
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.
3.1.2.2Location and study date
GEMINI-2: follow-up reported with the initial extension results
Treatment assignment according to response in GEMINI-1
Safety follow-up described in the subsequent publication
3.1.2.4Eligibility criteria
Prior participation requirement
Randomized maintenance treatment for initial responders
3.1.2.6.1Rationale for using adverse event incidence as the primary endpoint
Not applicable.
3.1.2.7Statistical analysis description
3.1.2.7.1Number of participants (Planned and analyzed)
GEMINI-2: sample size and power
3.1.2.7.2Description of analysis sets
GEMINI-2: statistical hypothesis
Prespecified analysis populations
Planned comparison of categorical efficacy outcomes
3.1.2.8.1Participant disposition
Extension enrollment and treatment groups
3.1.2.8.2Baseline characteristics
No evidence found.
3.1.2.8.3Efficacy results
GEMINI-2: maintenance and flare prevention
3.1.2.8.4Health-related quality of life and patient-reported outcomes
No evidence found.
GEMINI-2: serious adverse events and discontinuation
GEMINI-2: infusion reactions
Summary
The randomized maintenance comparison included 16 initial responders, eight per group, rather than all 42 extension participants. Its results therefore apply to a responder-enriched population. Other extension groups received nonrandomized treatment according to prior response. The statistical analysis plan specified no formal hypothesis and no formal sample size or power calculation. The small randomized groups limit precision for flare prevention and uncommon adverse events.
Imsidolimab in participants with GPP
3.1.3.2Location and study date
Geographic scope reported by the sponsor
3.1.3.4Eligibility criteria
Disease activity thresholds described in the sponsor report
3.1.3.6.1Rationale for using CGI response as the primary endpoint
Primary endpoint and assessment times
Independent validation of the primary response definition
No evidence found.
3.1.3.7Statistical analysis description
3.1.3.7.1Number of participants (Planned and analyzed)
3.1.3.7.2Description of analysis sets
Prespecified analysis populations
Sponsor-reported imputation for missing severity-index data
3.1.3.8.1Participant disposition
Enrollment and completion
3.1.3.8.2Baseline characteristics
Baseline disease burden in the sponsor results table
3.1.3.8.3Efficacy results
CGI response at both week 4 and week 16
GPPPGA response in the subgroup assessed after protocol amendment
3.1.3.8.4Health-related quality of life and patient-reported outcomes
DLQI change relative to baseline in the sponsor results table
Serious Staphylococcal aureus bacteremia: investigator causality assessment
Summary
GALLOP was open-label and single-arm, with eight participants enrolled and six completing the study. Without a randomized control group, observed improvement cannot establish the treatment effect separately from the natural course of a flare. GPPPGA results were reported for four participants after a protocol amendment, whereas CGI response used the full cohort. This limits comparison of the response percentages across instruments.
Spesolimab versus placebo during an acute GPP flare
3.1.4.2Location and study date
Trial dates and geographic scope
Randomized comparator trial
3.1.4.4Eligibility criteria
Acute-flare eligibility thresholds
Single intravenous spesolimab dose compared with placebo
3.1.4.6.1Rationale for using GPPGA pustulation subscore as the primary endpoint
Meaning of a pustulation subscore of zero at week 1
GPPGA and GPPASI validation
3.1.4.7Statistical analysis description
3.1.4.7.1Number of participants (Planned and analyzed)
Planned enrollment and power
3.1.4.7.2Description of analysis sets
Population for the primary and key secondary endpoints
Prespecified endpoint testing
3.1.4.8.1Participant disposition
Open-label spesolimab at week 1
3.1.4.8.2Baseline characteristics
3.1.4.8.3Efficacy results
Week 1 response: participants and percentages
Week 1 response comparisons
3.1.4.8.4Health-related quality of life and patient-reported outcomes
Week 4 symptom and fatigue endpoints after open-label treatment: analysis approach
Comparator trial: spesolimab, Effisayil 1
Summary
The trial enrolled 53 participants. The primary randomized comparison was assessed at week 1; subsequently, 12 participants initially assigned to spesolimab and 15 initially assigned to placebo received open-label spesolimab. This limits interpretation of later outcomes as randomized treatment comparisons. The publication consequently reported later symptom and fatigue outcomes descriptively. This was a placebo-controlled spesolimab study, not a comparison with imsidolimab.
Maintenance treatment and flare prevention
3.1.5.2Location and study date
Randomized dose-finding study
3.1.5.4Eligibility criteria
GPPPGA total score at screening and randomization
Investigated subcutaneous spesolimab regimens
3.1.5.6.1Rationale for using time to first GPP flare as the primary endpoint
Flare definition for the primary endpoint through week 48
GPPGA and GPPASI validation
3.1.5.7Statistical analysis description
3.1.5.7.1Number of participants (Planned and analyzed)
Screening and randomization
3.1.5.7.2Description of analysis sets
Prespecified time-to-event analyses
3.1.5.8.1Participant disposition
Randomized treatment groups
3.1.5.8.2Baseline characteristics
3.1.5.8.3Efficacy results
Participants with a GPP flare by week 48
High-dose spesolimab versus placebo: time to first flare
3.1.5.8.4Health-related quality of life and patient-reported outcomes
Definition of the symptom and quality-of-life endpoints
Time to worsening of the Psoriasis Symptom Scale
Time to worsening of the Dermatology Life Quality Index
Mortality during the trial
Summary
The trial enrolled participants with a history of at least two GPP flares who had clear or almost clear skin at screening and randomization. It therefore addresses flare prevention rather than initial treatment of an active flare. The high-dose group included 30 participants and the placebo group 31, limiting precision for uncommon harms. Follow-up for the primary endpoint extended to 48 weeks. The comparator was placebo, not imsidolimab.
Primary objective in the first-in-human study
3.1.6.2Location and study date
Healthy-volunteer trial design
Randomization ratio in the healthy-volunteer cohorts
3.1.6.4Eligibility criteria
Single ascending doses: studied range
Multiple ascending intravenous doses: studied range and frequency
3.1.6.6.1Rationale for using adverse event incidence as the primary endpoint
Not applicable.
3.1.6.7Statistical analysis description
3.1.6.7.1Number of participants (Planned and analyzed)
Healthy volunteers in the congress poster
3.1.6.7.2Description of analysis sets
Safety populations in the congress poster
Safety assessment method specified in the registry
3.1.6.8.1Participant disposition
Poster-reported assessment period
3.1.6.8.2Baseline characteristics
No evidence found.
3.1.6.8.3Efficacy results
Healthy-volunteer pharmacokinetics: half-life and subcutaneous bioavailability
Clinical efficacy in GPP
Not applicable.
3.1.6.8.4Health-related quality of life and patient-reported outcomes
Not applicable.
Treatment-emergent adverse events: participants and percentages
Serious adverse events across all participants in each dose-escalation part
Summary
The congress poster reports 72 healthy volunteers, including 48 in the single ascending dose cohorts and 24 in the multiple ascending dose cohorts, with an assessment period of 85 days. These data do not establish clinical efficacy in GPP or longer-term safety during chronic treatment. The registry lists 73 participants overall, whereas the poster reports 72 healthy volunteers; the available evidence in this report does not reconcile that difference.