Moderate-to-Severe Atopic Dermatitis
Conditions
Keywords
Atopic Dermatitis, Nemolizumab, CD14152
Brief summary
The purpose of this study was to assess the pharmacokinetics (PK), safety, and efficacy of nemolizumab in pediatric participants with moderate-to-severe atopic dermatitis (AD).
Interventions
DRUGNemolizumab
Participants will receive subcutaneous (SC) injection of 10, 20 or 30 milligrams (mg) nemolizumab, every 4 weeks (Q4W) for 52 weeks with a loading dose of 20, 40 or 60 mg at Day 1 based on the body weight.
Sponsors
Galderma R&D
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Chronic AD that has been documented for at least 6 months for participants aged 2-6 years and at least 1 year for participants aged 7-11 years before the screening visit and confirmed according to the American Academy of Dermatology Consensus Criteria at the time of the screening visit * EASI score \>=16 at both screening and baseline visits * IGA score \>=3 at both screening and baseline visits * AD involvement \>=10% of BSA at both screening and baseline visits * Peak (maximum) PP NRS score of at least 4.0 at both screening and baseline visits * Agree to apply a moisturizer throughout the study from the screening visit daily, and liberally as needed; agree to apply an authorized topical corticosteroids (TCS) from the screening visit and throughout the study as determined appropriate by the investigator * Participant and caregiver willing and able to comply with all of the time commitments and procedural requirements of the clinical trial protocol * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Body weight less than 10 kilogram (kg) * Child in Care: a child who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation * Participants with a current medical history of chronic bronchitis * Requiring rescue therapy for AD during the run-in period or expected to require rescue therapy within 2 weeks following the baseline visit * Positive serology results for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), hepatitis C (HCV) antibody with positive confirmatory test for HCV (example; polymerase chain reaction \[PCR\]), or human immunodeficiency virus (HIV) antibody at the screening visit * History of lymphoproliferative disease, hypersensitivity (including anaphylaxis) to an immunoglobulin product and intolerance to low or mid potency topical corticosteroids * Known or suspected immunosuppression * Participants unwilling to refrain from using prohibited medications during the clinical trial. * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nemolizumab Serum Concentrations | At Weeks 4, 8, 12, 16, 32 and 52 | Serum concentrations of Nemolizumab were analyzed using validated enzyme linked immunosorbent assay (ELISA). |
| Apparent Total Body Clearance (Cl/F) of Nemolizumab | Pre-dose at Weeks 4, 8, 12, 16, 32 and 52 | CL/F is apparent clearance of the drug from the serum, calculated as the drug dose divided area under the curve from time 0 extrapolated to infinite time \[AUC (0-inf)\]. Individual nemolizumab. |
| Apparent Volume of Distribution (Vd/F) of Nemolizumab | Pre-dose at Weeks 4, 8, 12, 16, 32 and 52 | Vd/F was calculated as dose divided by lambda\_z \*AUC(0-inf). |
| Absorption Rate Constant (Ka) of Nemolizumab | Pre-dose at Weeks 4, 8, 12, 16, 32 and 52 | — |
| Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Nemolizumab | Pre-dose at Weeks 4, 8, 12, and 16 | — |
| Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Nemolizumab | Pre-dose at Weeks 4, 8, 12, 16, 32 and 52 | — |
| Apparent Terminal Half-life (t1/2) of Nemolizumab | Pre-dose at Weeks 4, 8, 12, 16, 32 and 52 | — |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs), Adverse Events Leading to Discontinuation and Serious Adverse Events (SAEs) | Baseline through Week 52 | AE defined as any untoward medical occurrence in clinical study participant administered a medicinal product which does not necessarily have causal relationship with this treatment. TEAEs defined as AEs occurring after first administration of study drug during the study. SAE was any untoward medical occurrence, in view of either Investigator or Sponsor, that resulted in death, was life-threatening, resulted in inpatient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was important medical event. AESI was noteworthy TEAE for study drug that was to be monitored closely and reported promptly. Relatedness to study drug was based on Investigator's discretion. AEs Leading to study treatment withdrawal and AEs Leading to study withdrawal will also be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Each Visit up to Week 52 | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | EASI assesses severity and extent of AD signs through a composite score of erythema, induration/population, excoriation, and lichenification. The severity was assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. The EASI score ranged from 0 to 72 with higher scores representing greater severity of atopic dermatitis. |
| Absolute Change From Baseline in EASI Score | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | EASI assesses severity and extent of AD signs through a composite score of erythema, induration/population, excoriation, and lichenification. The severity was assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. The EASI score ranged from 0 to 72 with higher scores representing greater severity of atopic dermatitis. |
| Number of Participants Achieving 50 Percent (%), 75% or 90% Response From Baseline in EASI (EASI-50, EASI-75 and EASI-90) | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | EASI assesses severity and extent of AD signs through a composite score of erythema, induration/population, excoriation, and lichenification. The severity was assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. The EASI score ranged from 0 to 72 with higher scores representing greater severity of atopic dermatitis. EASI-50, EASI-75 and EASI-90 responders will be the participants who achieved greater than or equal to (\>=) 50%, \>=75% and \>=90% overall improvement in EASI score respectively from baseline to Week 52. |
| Number of Participants With Investigator's Global Assessment (IGA) Success Rate | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | IGA is a 5-point scale used by the investigator or trained designee to evaluate the global severity of AD. The Investigator reviewed the participant's skin and give a score of 0 (Clear), 1 (Almost clear), 2 (Mild), 3 (Moderate), or 4 (Severe). Here, higher score indicates severe outcome. Success was defined as an IGA of 0 \[Clear\] or 1 \[Almost clear\] and a \>=2-points improvement from baseline. Number of participants with IGA success rate was reported for this outcome measure. |
| Change From Baseline in Body Surface Area (BSA) Involvement by Atopic Dermatitis (AD) | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]) and reported as a percentage of all major body sections combined. The reported percentage of BSA was combined percentage of all major body sections. |
| Absolute Change From Baseline in Weekly Average of Peak Pruritus Numeric Rating Scale (PP NRS) Score | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | Pruritus NRS is a scale that will be used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicated worse outcome. |
| Percent Change From Baseline in Weekly Average of PP NRS Score | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | Pruritus NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicated worse outcome. |
| Percentage of Participants With an Improvement of >= 4 From Baseline in Weekly Average of PP NRS | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | Pruritus NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicated worse outcome. |
| Absolute Change From Baseline in Weekly Average of Average Pruritus NRS Score | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | Pruritus NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicated worse outcome. |
| Percent Change From Baseline in Weekly Average of Average Pruritus NRS Score | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | Pruritus NRS is a scale that was used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores were provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicated worse outcome. |
| Absolute Change From Baseline in Weekly Average of Sleep Disturbance NRS Score | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | The sleep disturbance NRS is a scale used by the participants to report the degree of their sleep loss related to AD. Participants were asked the following questions in their local language: how would you rate your sleep last night? On a scale of 0 to 10, with 0 being 'no sleep loss related to signs/symptoms of AD' and 10 being 'I cannot sleep at all due to the signs/symptoms of AD'. Higher scores indicated worse outcome. |
| Percent Change From Baseline in Weekly Average of Sleep Disturbance NRS Score | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | The sleep disturbance NRS is a scale used by the participants to report the degree of their sleep loss related to AD. Participants were asked the following questions in their local language: how would you rate your sleep last night? On a scale of 0 to 10, with 0 being 'no sleep loss related to signs/symptoms of AD' and 10 being 'I cannot sleep at all due to the signs/symptoms of AD'. Higher scores indicated worse outcome. |
| Percentage of Participants Receiving Any Rescue Therapy by Rescue Treatment | From Baseline up to Week 52 | Percentage of participants receiving any rescue therapy by rescue treatment was reported. |
| Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | SCORAD is a clinical tool for assessing the severity and the extent of AD signs and symptoms. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranged from 0 (absent disease) to 103 (severe disease), a higher score indicated severe disease. |
| Change From Baseline in Children's Dermatology Life Quality Index (cDLQI) For Participants >=4 Years of Age | Baseline, Week 16 and Week 52 | The DLQI is a validated 10-item questionnaire covering domains including symptoms/feelings, daily activities, leisure, work/school, personal relationships, and treatment. The participant rated each question ranging from 0 (not at all) to 3 (very much) and score ranged from 0 to 30. A higher total score indicated a poorer quality of life (QoL). |
| Change From Baseline in Infants' Dermatology Life Quality Index (iDLQI) Score For Participants Less Than (<) 4 Years of Age | Baseline, Week 16 and Week 52 | The DLQI is a validated 10-item questionnaire covering domains including symptoms/feelings, daily activities, leisure, work/school, personal relationships, and treatment. The participant rated each question ranging from 0 (not at all) to 3 (very much) and score ranged from 0 to 30. A higher total score indicated a poorer QoL. |
| Change From Baseline in Patient-Oriented Eczema Measure (POEM) | Baseline, Week 16 and Week 52 | The POEM is a 7-item questionnaire that assessed disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease). A high score indicated poor QOL. |
| Pharmacokinetic (PK)/Pharmacodynamic (PD) Relationship Between Nemolizumab Serum Concentration and Changes in PP NRS | Baseline up to Week 52 | The relationship between nemolizumab serum concentrations and changes in PP-NRS score was established using population point estimate of IC50, where IC50 is the concentration leading to half of the maximum drug-induced reduction (Imax) in PP NRS. |
| PK/PD Relationship Between Nemolizumab Serum Concentration and Changes in EASI Score | Baseline up to Week 52 | The relationship between nemolizumab serum concentrations and changes in EASI score was established using population point estimate of IC50. Where, IC50 is the concentration leading to half of the maximum drug-induced reduction (Imax) in EASI score. |
| PK/PD Relationship Between Nemolizumab Serum Concentration and Changes in IGA Score | Baseline up to Week 52 | The relationship between nemolizumab serum concentrations and changes in IGA score was established using the population point estimate of the slope parameter. |
| Number of Participants With Positive Anti-Drug Antibody (ADA) for Nemolizumab | Baseline, Week 16 and Week 52 | ADA positive was defined as a sample that was evaluated as positive in both the ADA screening and confirmatory assays. ADA positive participants was defined as participants who had at least 1 positive ADA result. |
Countries
Denmark, Hungary, Poland, Spain, United States
Participant flow
Recruitment details
The study was conducted at 23 sites in the United States, Denmark, Hungary, Poland and Spain from 24 June 2021 to 28 April 2025.
Pre-assignment details
A total of 109 participants were enrolled in this study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 7.1 years STANDARD_DEVIATION 2.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 108 Participants |
| Sex: Female, Male Female | 52 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 37 | 0 / 36 |
| other Total, other adverse events | 30 / 36 | 32 / 37 | 32 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 37 | 0 / 36 |
Outcome results
None listed