A Study to Test Whether Spesolimab Helps People With a Skin Disease Called Netherton Syndrome

Phase 3TerminatedNCT05856526

Boehringer Ingelheim43 enrolled

Overview

This study is open to people with a skin disease called Netherton syndrome (NS). People can join the study if they are 12 years or older. The purpose of this study is to find out whether a medicine called spesolimab helps people with NS. Participants are divided into a spesolimab and a placebo group. Placebo injections look like spesolimab injections but do not contain any medicine. Every participant has a 2 in 3 chance of being in the spesolimab group. In the beginning, participants get the study medicine as an injection into a vein. Afterwards, they get it as an injection under the skin every month. After 4 months, participants in the placebo group switch to spesolimab treatment. Participants are in the study for up to 3 years. During this time, they visit the study site up to 42 times. The doctors regularly check participants' NS symptoms. The results are compared between the groups to see whether spesolimab works. The doctors also regularly check participants' general health and take note of any unwanted effects.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Netherton Syndrome

Interventions

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female patients, aged 12 years and older (weight minimum is 35kg). * Confirmed diagnosis of Netherton syndrome (NS) (causative SPINK5 mutations) at baseline (Visit 2). * At least moderate severity of erythema at baseline (visit 2) (Ichthyosis Area Severity Index (IASI) score ≥ 16 and IASI-Erythema (E) score ≥8) and ≥ 3 on Investigator Global Assessment (IGA) score. * Signed and dated written informed consent and assent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission in the trial * Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the clinical trial protocol (CTP) as well as in the patient, parent(s) (or patient's legal guardian) information. Exclusion Criteria: * Patients who have used topical corticosteroids (medium to high, US class I-V), topical retinoids, topical calcineurin inhibitors or keratolytics within 1 week prior to randomisation * Patients who have used emollient on the area to be biopsied in the previous 24 hours * Patients who have used systemic retinoids, other systemic immunosuppressants, systemic corticosteroids or phototherapy within 4 weeks prior to randomisation * Patients who have used systemic antibiotics within 2 weeks prior to randomisation * Patients who have received live vaccines within 4 weeks prior to randomisation * Patients who have received investigational products, biologics or immunoglobulins within 4 weeks or 5 half-lives (whichever is longer) prior to randomisation * Severe, progressive, or uncontrolled hepatic disease, defined as \>3-fold Upper Limit of Normal (ULN) elevation in Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) or alkaline phosphatase, or \>2-fold ULN elevation in total bilirubin * Patients who have any prior exposure to BI 655130 or another interleukin 36 receptor (IL-36R) inhibitor biologics * Further exclusion criteria apply

Locations (28)

Mission Dermatology Center

Rancho Santa Margarita, California, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Virginia Clinical Research, Inc.

Norfolk, Virginia, United States

Westmead Hospital

Westmead, New South Wales, Australia

Outcomes

Primary Outcomes

IASI Response, Defined as a Decrease of at Least 50% Absolute Change in IASI Score From Baseline at Week 16 (Yes/No)

Proportion of participants with an Ichthyosis Area Severity Index (IASI) response at Week 16 is reported. IASI response was defined as a decrease of at least 50% absolute change in IASI score from baseline at Week 16. Proportions were rounded to 3 decimal places. IASI is a composite score based on the global Congenital Ichthyosis Severity Instrument (CISI) score that captures differences in severity in different body regions as a function of their body surface area, and also standardizes the number of choices within the Likert scales for erythema and scaling. The score ranges from 0-48 (sum of a max score of 24 for erythema and 24 for scaling). A higher score means worse clinical severity. 95% confidence intervals (CI) are calculated using the method of Wilson.

Time frame: At baseline and at Week 16.

Secondary Outcomes

Key Secondary Endpoint: IGA Response, Defined as a Decrease of at Least 1-grade Absolute Change in IGA Score From Baseline at Week 16 (Yes/No)

Proportion of participants with an Investigator Global Assessment (IGA) response at Week 16 is reported. Proportions were rounded to 3 decimal places. IGA response was defined as a decrease of at least 1-grade absolute change in IGA score from baseline at Week 16. IGA for Netherton Syndrome (NS) assessed the global severity of erythema and scaling in NS using a 5-point Likert scale ranging from 0=clear, to 4=severe. 95% confidence intervals (CI) are calculated using the method of Wilson.

Time frame: Baseline and at Week 16 after start of study treatment administration.

IGA Score of 0 or 1 at Weeks 4, 8, 12 and 16 (Yes/No)

Proportion of participants with an Investigator Global Assessment (IGA) score of 0 or 1 at Week 4, at Week 8, at Week 12 and at Week 16 after first study treatment administration is reported. Proportions were rounded to 3 decimal places. IGA for Netherton Syndrome (NS) assessed the global severity of erythema and scaling in NS using a 5-point Likert scale ranging from 0=clear, to 4=severe. 95% confidence intervals (CI) are calculated using the method of Wilson.

Time frame: At Week 4, at Week 8, at Week 12, at Week 16 after start of study treatment administration.

IASI Response, Defined as a Decrease of at Least 50% Absolute Change in IASI Score From Baseline at Weeks 4, 8, and 12 (Yes/No)

Proportion of participants with an Ichthyosis Area Severity Index (IASI) response at Weeks 4, 8, 12 is reported. Proportions were rounded to 3 decimal places. IASI response was defined as a decrease of at least 50% absolute change in IASI score from baseline at Week 4, Week 8 and Week 12. IASI is a composite score based on the global Congenital Ichthyosis Severity Instrument (CISI) score that captures differences in severity in different body regions as a function of their body surface area, and also standardizes the number of choices within the Likert scales for erythema and scaling. The score ranges from 0-48 (sum of a max score of 24 for erythema and 24 for scaling). A higher score means worse clinical severity. 95% confidence intervals (CI) are calculated using the method of Wilson.

Time frame: At baseline and at Week 4, at Week 8, at Week 12 after start of study treatment administration.

IASI-E Subscore Response, Defined as a Decrease of at Least 50% Absolute Change in IASI-E Subscore at Weeks 4, 8, 12, and 16 (Yes/No)

Proportion of participants with an Ichthyosis Area Severity Index-Erythema (IASI-E) subscore response at Weeks 4, 8, 12 and 16 is reported. Proportions were rounded to 3 decimal places. IASI-E response was defined as a decrease of at least 50% absolute change in IASI-E subscore from baseline at Week 4, at Week 8, at Week 12 and at Week 16. IASI-E is a composite score based on the global Congenital Ichthyosis Severity Instrument (CISI) score that captures differences in severity in different body regions as a function of their body surface area, and also standardizes the number of choices within the Likert scales for erythema. The score ranges from 0-24. A higher score means worse clinical severity. 95% confidence intervals (CI) are calculated using the method of Wilson.

Time frame: At baseline and at Week 4, at Week 8, at Week 12, at Week 16 after start of study treatment administration.

IASI-S Subscore Response, Defined as a Decrease of at Least 50% Absolute Change in IASI-S Subscore From Baseline at Weeks 4, 8, 12, and 16 (Yes/No)

Proportion of participants with an Ichthyosis Area Severity Index-Scaling (IASI-S) subscore response at Weeks 4, 8, 12 and 16 is reported. Proportions were rounded to 3 decimal places. IASI-S response was defined as a decrease of at least 50% absolute change in IASI-S subscore from baseline at Week 4, at Week 8, at Week 12 and at Week 16. IASI-S is a composite score based on the global Congenital Ichthyosis Severity Instrument (CISI) score that captures differences in severity in different body regions as a function of their body surface area, and also standardizes the number of choices within the Likert scales for scaling. The score ranges from 0-24. A higher score means worse clinical severity. 95% confidence intervals (CI) are calculated using the method of Wilson.

Time frame: At baseline and at Week 4, at Week 8, at Week 12, at Week 16 after start of study treatment administration.

Percent Change From Baseline in IASI Score at Weeks 4, 8, 12 and 16

Percent change from baseline in IASI score at Weeks 4, 8, 12 and 16 is reported. IASI is a composite score based on the global Congenital Ichthyosis Severity Instrument (CISI) score that captures differences in severity in different body regions as a function of their body surface area, and also standardizes the number of choices within the Likert scales for erythema and scaling. The score ranges from 0-48 (sum of a max score of 24 for erythema and 24 for scaling). A higher score means worse clinical severity. Percent change of IASI score= (IASI score at Week X - IASI score at baseline)\*100/(IASI score at baseline). Week X=4, 8, 12, 16. Least Squares Mean (95% Confidence Interval) were calculated using mixed effect model with repeated measures (MMRM) which included the fixed, categorical effects of treatment at each visit, age group and the continuous effect of baseline at each visit as well as random effects of subject.

Time frame: MMRM model included measurements from baseline and Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 68 after study treatment administration. MMRM values of percent change from baseline at Week 4, 8, 12, 16 are presented.

Absolute Change From Baseline in NRS Pain at Weeks 4, 8, 12 and 16

Absolute change from baseline in Numeric Pain Rating Scale (NRS) pain at Weeks 4, 8, 12 and 16 is presented. The NRS is a unidimensional measure of pain intensity, including chronic pain. The 11-point numeric scale ranges from '0' representing 'no pain' to '10' representing worst pain imaginable. Absolute change in NRS at Week X= (NRS pain at Week X) - (NRS pain at baseline). Week X= 4, 8, 12, 16. Least Squares Mean (95% Confidence Interval) were calculated using mixed effect model with repeated measures (MMRM) which included the fixed, categorical effects of treatment at each visit, age group and the continuous effect of baseline at each visit as well as random effects of subject.

Time frame: MMRM model included measurements from baseline and Week 4, 8, 12, 16, 20, 24, 28, 32, 40, 52, 64 after study treatment administration. MMRM values of absolute change from baseline in NRS pain at Week 4, 8, 12, 16 are presented.

Absolute Change From Baseline in NRS Itch at Weeks 4, 8, 12 and 16

The Numeric Pain Rating Scale (NRS) itch measures the intensity of itch. The scale ranges from '0' representing 'no itch' to 10 'worst imaginable itch'. Absolute change in NRS itch at Week X= (NRS itch at Week X) - (NRS itch at baseline). Week X= 4, 8, 12, 16. Least Squares Mean (95% Confidence Interval) were calculated using mixed effect model with repeated measures (MMRM) which included the fixed, categorical effects of treatment at each visit, age group and the continuous effect of baseline at each visit as well as random effects of subject.

Absolute Change From Baseline in DLQI Score at Weeks 8 and 16

Dermatology Life Quality Index (DLQI) assesses various dermatologic conditions and it measures the quality of life. It contains 10 questions which are score from 0 (not relevant) to 3 (very much). Question 7 is a "yes"/ "no" question where "yes" is scored as 3. Total score ranges from 0 to 30 in total. Scores of 0-1 indicate no effect, scores of 2-5 indicate a small effect, scores of 6-10 indicate moderate effect, score 11-20 indicate very large effect and scores 21-30 indicate an extremely large effect of the syndrome on the participant. Absolute change in DLQI score at Week X= (DLQI score at Week X) - (DLQI score at baseline). Week X= 8, 16. Least Squares Mean (95% Confidence Interval) were calculated using mixed effect model with repeated measures (MMRM) which included the fixed, categorical effects of treatment at each visit, age group and the continuous effect of baseline at each visit as well as random effects of subject.

Time frame: MMRM model included measurements from baseline and Week 8, 16, 24, 32, 52, after study treatment administration. MMRM values of absolute change from baseline in DLQI score at Week 8, 16 are presented.

Absolute Change From Baseline in CDLQI Score at Weeks 8 and 16

Children's Dermatology Life Quality Index (CDLQI) measures the impact of skin disease on the lives of children and young people. CDLQI total score is calculated by summing the scores of each question resulting in a range of 0 to 30. Scores of 0-1 indicate no effect, scores of 2-6 indicate a small effect, scores of 7-12 indicate moderate effect, score 13-18 indicate very large effect and scores 19-30 indicate an extremely large effect of the syndrome on the participant. Absolute change in CDLQI score at Week X= (CDLQI score at Week X) - (CDLQI score at baseline). Week X= 8, 16.

Time frame: At baseline and at Week 8 and at Week 16 after study treatment administration.

The Occurrence of Treatment Emergent Adverse Events Including Serious and/or Opportunistic Infections

Percentage of patients with treatment emergent adverse events including serious and/or opportunistic infections is presented. Percentages are rounded to one decimal place.

Time frame: From first study treatment administration until end of randomised period (Week 16) plus 16 weeks of residual effect period, up to 32 weeks.