Trial Outcomes & Findings for Spesolimab (BI 655130) Single Dose in Generalized Pustular Psoriasis (NCT NCT02978690)

NCT ID: NCT02978690

Last Updated: 2023-08-21

Results Overview

Percentage of patients with adverse reactions, defined as drug-related Adverse Events is presented.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

7 participants

Primary outcome timeframe

Up to 140 days from the administration of spesolimab.

Results posted on

2023-08-21

Participant Flow

At the screening visit, patients had to be on stable maintenance treatment (for at least 4 weeks) with retinoids and/or methotrexate or not to receive any maintenance therapy at all. All patients were to use an effective birth control method throughout the trial.

This exploratory, Phase I, multi-centre, multi-national trial in male and female patients with a flare of Generalised Pustular Psoriasis (GPP) applied an open-label design.

Participant milestones

Participant milestones
Measure
Spesolimab
Patients received a single intravenous dose of 10 milligram/kilogram (mg/kg) body weight spesolimab (BI 655130) in an open label manner. The intravenous infusion over 60 minutes (min), could be prolonged by the investigator up to 240 min. Patients were to be followed up for 140 days (20 weeks) after dosing.
Overall Study
STARTED
7
Overall Study
COMPLETED
7
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Spesolimab (BI 655130) Single Dose in Generalized Pustular Psoriasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Spesolimab
n=7 Participants
Patients received a single intravenous dose of 10 milligram/kilogram (mg/kg) body weight spesolimab (BI 655130) in an open label manner. The intravenous infusion over 60 minutes (min), could be prolonged by the investigator up to 240 min. Patients were to be followed up for 140 days (20 weeks) after dosing.
Age, Continuous
38.6 years
STANDARD_DEVIATION 13.8 • n=5 Participants
Sex: Female, Male
Female
4 Participants
n=5 Participants
Sex: Female, Male
Male
3 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
7 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
4 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
2 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Up to 140 days from the administration of spesolimab.

Population: Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).

Percentage of patients with adverse reactions, defined as drug-related Adverse Events is presented.

Outcome measures

Outcome measures
Measure
Spesolimab
n=7 Participants
Patients received a single intravenous dose of 10 milligram/kilogram (mg/kg) body weight spesolimab (BI 655130) in an open label manner. The intravenous infusion over 60 minutes (min), could be prolonged by the investigator up to 240 min. Patients were to be followed up for 140 days (20 weeks) after dosing.
Percentage of Patients With Adverse Reactions, Defined as Drug-related Adverse Events (AE)
57.1 percentage of participants

SECONDARY outcome

Timeframe: At baseline and at Week 2.

Population: Full Analysis Set Last Observation Carry forward (FAS LOCF). Full Analysis Set (FAS): All patients in the treated set (TS) who had a baseline and at least one post baseline GPP Area and Severity Index (GPPASI) or GPP Physician Global Assessment (GPPGA) measurement and no important protocol violation flagged for exclusion from the FAS. LOCF: The last available value, including baseline, was carried forward to all subsequent visits within the on-treatment period at which a measurement was missing.

The GPPASI is an adaptation for Generalized Pustular Psoriasis (GPP) patients of the Psoriasis Area and Severity Index (PASI), an established measure of severity and area of psoriatic lesions in patients with psoriasis. It is a tool which provides a numeric scoring for patients overall GPP disease state, ranging from 0 (no disease) to 72 (worse disease state). It is a linear combination of percent of surface area of skin that is affected and the severity of erythema, pustules, and scaling (desquamation) over four body regions. % GPPASI change from baseline=100\* (GPPASI at baseline - GPPASI at post-baseline visit)/(GPPASI at baseline). For %GPPASI change, positive numbers show reduction in GPPASI with higher values representing a larger improvement or recovery of disease, while negative numbers show an increase in GPPASI, i.e. worsening of disease.

Outcome measures

Outcome measures
Measure
Spesolimab
n=7 Participants
Patients received a single intravenous dose of 10 milligram/kilogram (mg/kg) body weight spesolimab (BI 655130) in an open label manner. The intravenous infusion over 60 minutes (min), could be prolonged by the investigator up to 240 min. Patients were to be followed up for 140 days (20 weeks) after dosing.
Percent Change From Baseline in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) Total Score at Week 2
73.2 percent GPPASI change
Standard Deviation 16.2

SECONDARY outcome

Timeframe: At Week 2.

Population: Full Analysis Set No Response Imputed (FAS NRI). Full Analysis Set (FAS): All patients in the treated set (TS) who had a baseline and at least one post baseline GPP Area and Severity Index (GPPASI) or GPP Physician Global Assessment (GPPGA) measurement and no important protocol violation flagged for exclusion from the FAS. NRI: If there were data at the visits both immediately before and immediately after the visit with a missing outcome, a failure to achieve response imputed.

GPPGA relies on clinical assessment of the GPP patient's skin presentation. It is a modified Physician Global Assessment (PGA), a physician's assessment of psoriatic lesions, which has been adapted to the evaluation of GPP patients. The investigator (or qualified site personnel) scores the erythema, pustules and scaling of all psoriatic lesions from 0 - 4. Each component is graded separately, the average is calculated and the final GPPGA is determined from this composite score. A lower score then indicates a lesser severity, with 0 being clear and 1 being almost clear. To receive a score of 0 or 1, the patient should be afebrile, in addition to skin presentation requirements.

Outcome measures

Outcome measures
Measure
Spesolimab
n=7 Participants
Patients received a single intravenous dose of 10 milligram/kilogram (mg/kg) body weight spesolimab (BI 655130) in an open label manner. The intravenous infusion over 60 minutes (min), could be prolonged by the investigator up to 240 min. Patients were to be followed up for 140 days (20 weeks) after dosing.
Proportion of Patients With Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Total Score of 0 (Clear) or 1 (Almost Clear) at Week 2
0.714 proportion of patients

SECONDARY outcome

Timeframe: At baseline and at Week 2.

Population: Full Analysis Set Last Observation Carry forward (FAS LOCF). Full Analysis Set (FAS): All patients in the treated set (TS) who had a baseline and at least one post baseline GPP Area and Severity Index (GPPASI) or GPP Physician Global Assessment (GPPGA) measurement and no important protocol violation flagged for exclusion from the FAS. LOCF: The last available value, including baseline, was carried forward to all subsequent visits within the on-treatment period at which a measurement was missing.

Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale scale score at Week 2 is presented. The FACIT-Fatigue scale is a brief and reliable instrument for monitoring fatigue and its effects on patients. It is a comprehensive compilation of questions that measure health-related quality of life in patients with chronic illnesses. It comprises 13 questions, the responses to which are each recorded on a 5-point Likert scale. Scores range from 0 to 52, with lower scores representing greater fatigue, i.e. higher changes from baseline indicate higher improvement (compared to baseline)

Outcome measures

Outcome measures
Measure
Spesolimab
n=7 Participants
Patients received a single intravenous dose of 10 milligram/kilogram (mg/kg) body weight spesolimab (BI 655130) in an open label manner. The intravenous infusion over 60 minutes (min), could be prolonged by the investigator up to 240 min. Patients were to be followed up for 140 days (20 weeks) after dosing.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at Week 2
12.3 units on a scale
Standard Deviation 10.1

SECONDARY outcome

Timeframe: At baseline and at Week 2.

Population: Full Analysis Set Last Observation Carry forward (FAS LOCF). Full Analysis Set (FAS): All patients in the treated set (TS) who had a baseline and at least one post baseline GPP Area and Severity Index (GPPASI) or GPP Physician Global Assessment (GPPGA) measurement and no important protocol violation flagged for exclusion from the FAS. LOCF: The last available value, including baseline, was carried forward to all subsequent visits within the on-treatment period at which a measurement was missing.

The pain VAS is a unidimensional measure of pain intensity. It is a continuous scale comprised of a horizontal or vertical line, usually 10 centimeters (100 millimeters (mm) in length, anchored by word descriptors at each end ('no pain', 'very severe pain'). The pain VAS is self-completed by the respondent. The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the 'no pain' anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity, i.e., a negative change from baseline indicates an improvement (compared to baseline).

Outcome measures

Outcome measures
Measure
Spesolimab
n=7 Participants
Patients received a single intravenous dose of 10 milligram/kilogram (mg/kg) body weight spesolimab (BI 655130) in an open label manner. The intravenous infusion over 60 minutes (min), could be prolonged by the investigator up to 240 min. Patients were to be followed up for 140 days (20 weeks) after dosing.
Change From Baseline in Pain Visual Analog Scale (VAS) Score at Week 2
-45.9 units on a scale
Standard Deviation 32.3

SECONDARY outcome

Timeframe: Within 1.5 hours (h) before and 0.5 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 312 h, 480 h, 648 h, 1992 h, 3336 h after spesolimab administration.

Population: Pharmacokinetic (PK) parameter set (PKS): All patients in the treated set (TS) who provided at least one secondary PK endpoint not flagged for exclusion due to a protocol violation relevant to the evaluation of PK (to be decided no later than at the Report Planning Meeting) or due to PK non-evaluability (as revealed during data analysis).

Area under the concentration-time curve of spesolimab in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.

Outcome measures

Outcome measures
Measure
Spesolimab
n=6 Participants
Patients received a single intravenous dose of 10 milligram/kilogram (mg/kg) body weight spesolimab (BI 655130) in an open label manner. The intravenous infusion over 60 minutes (min), could be prolonged by the investigator up to 240 min. Patients were to be followed up for 140 days (20 weeks) after dosing.
Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
2350 microgram (μg)·day/ milliliter (mL)
Geometric Coefficient of Variation 41.1

SECONDARY outcome

Timeframe: Within 1.5 hours (h) before and 0.5 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 312 h, 480 h, 648 h, 1992 h, 3336 h after spesolimab administration.

Population: Pharmacokinetic (PK) parameter set (PKS): All patients in the treated set (TS) who provided at least one secondary PK endpoint not flagged for exclusion due to a protocol violation relevant to the evaluation of PK (to be decided no later than at the Report Planning Meeting) or due to PK non-evaluability (as revealed during data analysis).

Maximum measured concentration of spesolimab in plasma (Cmax) is reported.

Outcome measures

Outcome measures
Measure
Spesolimab
n=6 Participants
Patients received a single intravenous dose of 10 milligram/kilogram (mg/kg) body weight spesolimab (BI 655130) in an open label manner. The intravenous infusion over 60 minutes (min), could be prolonged by the investigator up to 240 min. Patients were to be followed up for 140 days (20 weeks) after dosing.
Maximum Measured Concentration of Spesolimab in Plasma (Cmax)
203 microgram (μg)/milliliter (mL)
Geometric Coefficient of Variation 11.1

Adverse Events

Spesolimab

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Spesolimab
n=7 participants at risk
Patients received a single intravenous dose of 10 milligram/kilogram (mg/kg) body weight spesolimab (BI 655130) in an open label manner. The intravenous infusion over 60 minutes (min), could be prolonged by the investigator up to 240 min. Patients were to be followed up for 140 days (20 weeks) after dosing.
Blood and lymphatic system disorders
Eosinophilia
28.6%
2/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Gastrointestinal disorders
Abdominal pain
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Gastrointestinal disorders
Diarrhoea
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Gastrointestinal disorders
Vomiting
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
General disorders
Asthenia
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
General disorders
Chills
28.6%
2/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
General disorders
Oedema peripheral
28.6%
2/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
General disorders
Pain
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
General disorders
Pyrexia
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Infections and infestations
Pharyngitis
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Infections and infestations
Rash pustular
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Infections and infestations
Upper respiratory tract infection
28.6%
2/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Infections and infestations
Urinary tract infection
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Infections and infestations
Viral tonsillitis
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Injury, poisoning and procedural complications
Infusion related reaction
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Investigations
Blood creatine phosphokinase increased
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Musculoskeletal and connective tissue disorders
Arthralgia
42.9%
3/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Musculoskeletal and connective tissue disorders
Pain in extremity
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Renal and urinary disorders
Haematuria
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Renal and urinary disorders
Nephrolithiasis
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Renal and urinary disorders
Renal cyst
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Reproductive system and breast disorders
Pelvic pain
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Skin and subcutaneous tissue disorders
Eczema
28.6%
2/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Skin and subcutaneous tissue disorders
Pustular psoriasis
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Skin and subcutaneous tissue disorders
Skin fragility
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).
Skin and subcutaneous tissue disorders
Skin striae
14.3%
1/7 • Up to 140 days from the administration of spesolimab.
Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Results disclosure agreements

  • Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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Restriction type: OTHER