Dermatitis, Atopic
Conditions
Keywords
Eczema, AD, Vaccine, Nemolizumab, Pruritis, Itchy
Brief summary
The purpose of this study is to assess the effect of nemolizumab (CD14152) on humoral immune responses to tetanus and meningococcal vaccination in adult and adolescent participants with moderate-to-severe atopic dermatitis (AD).
Detailed description
This is a randomized, double-blind, placebo-controlled, multi-center, parallel-group study in adult and adolescent participants (≥ 12 to 54 years) with moderate-to-severe AD. Eligible participants must have a documented history of inadequate response to topical AD medication(s). Approximately 200 participants were randomized 1:1 to receive either 30 mg nemolizumab (with a 60 mg loading dose) or placebo, stratified by baseline disease severity Investigator Global Assessment (IGA) (IGA = 3, moderate; IGA = 4, severe). The study consisted of a 2- to 4-week screening period, a 16-week treatment period, and an 8-week follow-up period (12 weeks after the last study drug injection).
Interventions
DRUGNemolizumab
Nemolizumab was administered by 2 SC injections as 60-mg loading dose at baseline and a single 30-mg dose at Weeks 4, 8, and 12.
DRUGPlacebo
Placebo was administered by 2 SC injections at baseline and a single dose at Weeks 4, 8, and 12.
Sponsors
Galderma R&D
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 54 Years
Healthy volunteers
No
Inclusion criteria
* Chronic AD for at least 2 years * EASI score \>= 16 * IGA score \>= 3 * AD involvement \>= 10% of BSA * Peak (maximum) pruritus NRS score of at least 4.0
Exclusion criteria
* Body weight \< 30 kilogram (kg) * History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody) or to any of the study drug excipients * History of severe allergic reaction to either vaccine or to vaccine components including alum, thimerosal, phenol * Participants for whom administration of the meningococcal vaccine provided in this study is contraindicated or medically inadvisable * Participants for whom administration of the tetanus, diphtheria, and pertussis vaccine provided in this study is contraindicated or medically inadvisable * Receipt of any vaccine (except inactivated influenza vaccine) within 12 weeks prior to screening, any meningococcal vaccine within 1 year prior to screening, or any tetanus-, diphtheria-, or pertussis-containing vaccine within 5 years prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Positive Serum Immunoglobulin G (IgG) Response (>= 4-Fold Increase or >= 0.2 IU/mL in Anti-Tetanus IgG Concentrations) to Tetanus Toxoid at Week 16 (4 Weeks Post-vaccination) | At Week 16 (4 weeks post-vaccination) | Percentage of participants with a positive serum IgG response to tetanus toxoid, defined as greater than or equal to (\>=) 4-fold increase in anti-tetanus IgG concentrations from baseline in participants with pre-vaccination anti-tetanus IgG concentrations \>= 0.1 international unit per milliliter (IU/mL); or \>= 0.2 IU/mL anti-tetanus IgG concentrations in participants with pre-vaccination antitetanus IgG concentrations less than (\<) 0.1 IU/mL, at Week 16 (4 weeks post-vaccination) were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Positive Serum IgG Response (>=2-Fold Increase or >= 0.2 IU/mL in Anti-tetanus IgG Concentrations) to Tetanus Toxoid at Week 16 (4 Weeks Post-vaccination) | At Week 16 (4 weeks post-vaccination) | Percentage of participants with a positive serum IgG response to tetanus toxoid, defined as \>= 2-fold increase in anti-tetanus IgG concentrations from baseline in participants with pre-vaccination anti-tetanus IgG concentrations \>= 0.1 IU/mL; or \>= 0.2 IU/mL anti-tetanus IgG concentrations in participants with pre-vaccination Anti tetanus IgG concentrations \< 0.1 IU/mL, at Week 16 (4 weeks post-vaccination) were reported. |
| Percentage of Participants With Serum Anti-tetanus IgG Concentrations of >= 0.1 IU/mL at Week 16 | At Week 16 | Percentage of participants with serum anti-tetanus IgG concentrations of \>= 0.1 IU/mL at Week 16 were reported. The detection and characterization of antibodies to tetanus toxoid was performed using a validated immunoassay. |
| Percentage of Participants With Serum Anti-tetanus IgG Concentrations of >= 1.0 IU/mL at Week 16 | At Week 16 | Percentage of participants with serum anti-tetanus IgG concentrations of \>= 1.0 IU/mL at Week 16 were reported. The detection and characterization of antibodies to tetanus toxoid was performed using a validated immunoassay. |
| Percentage of Participants With a Positive Serum Bactericidal Antibody (SBA) Response to Meningococcal Serogroup C (MenC) Polysaccharide at Week 16 | At Week 16 | Percentage of participants with a positive SBA response to meningococcal serogroup C polysaccharide, defined as \>= 4-fold increase in SBA reciprocal titer from baseline (using non-imputed values), at Week 16 (4 weeks postvaccination) were reported. |
| Percentage of Participants With a Positive SBA Response (Defined as SBA Reciprocal Titer ≥8) to MenC Polysaccharide at Week 16 | At Week 16 | Percentage of participants with a positive SBA response to MenC polysaccharide, defined as SBA reciprocal titer \>= 8, at Week 16 were reported. Immune response to meningococcal vaccination was determined by measuring functional antibody responses using an SBA assay. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 42 sites in United states from 05 Mar 2020 to 07 Jul 2023.
Pre-assignment details
A total of 242 participants were randomized and out of which only 234 received treatment in the study.
Participants by arm
| Arm | Count |
|---|---|
| Nemolizumab Participants received a loading dose of nemolizumab (60 mg) via 2 SC injections at baseline. Nemolizumab (30 mg) administered via a single SC injection Q4W at Weeks 4, 8, and 12. Participants also received single doses of Tdap and MCV4 vaccines. | 123 |
| Placebo Participants received a placebo (matching to Nemolizumab) via 2 SC injections at baseline. Placebo was administered via a single subcutaneous injection Q4W at Weeks 4, 8, and 12. Participants also received single doses of Tdap and MCV4 vaccines. | 119 |
| Total | 242 |
Baseline characteristics
| Characteristic | Placebo | Total | Nemolizumab |
|---|---|---|---|
| Age, Continuous | 32.1 Years STANDARD_DEVIATION 12 | 33.6 Years STANDARD_DEVIATION 11.89 | 35.2 Years STANDARD_DEVIATION 11.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 88 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 152 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 32 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants | 66 Participants | 35 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 62 Participants | 132 Participants | 70 Participants |
| Sex: Female, Male Female | 69 Participants | 147 Participants | 78 Participants |
| Sex: Female, Male Male | 50 Participants | 95 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 119 | 0 / 115 |
| other Total, other adverse events | 44 / 119 | 38 / 115 |
| serious Total, serious adverse events | 0 / 119 | 1 / 115 |
Outcome results
Primary
Percentage of Participants With a Positive Serum Immunoglobulin G (IgG) Response (>= 4-Fold Increase or >= 0.2 IU/mL in Anti-Tetanus IgG Concentrations) to Tetanus Toxoid at Week 16 (4 Weeks Post-vaccination)
Percentage of participants with a positive serum IgG response to tetanus toxoid, defined as greater than or equal to (\>=) 4-fold increase in anti-tetanus IgG concentrations from baseline in participants with pre-vaccination anti-tetanus IgG concentrations \>= 0.1 international unit per milliliter (IU/mL); or \>= 0.2 IU/mL anti-tetanus IgG concentrations in participants with pre-vaccination antitetanus IgG concentrations less than (\<) 0.1 IU/mL, at Week 16 (4 weeks post-vaccination) were reported.
Time frame: At Week 16 (4 weeks post-vaccination)
Population: mITT population consisted of all randomized participants who received at least one dose of study drug and vaccine injection, had an evaluable vaccine response and did not receive any systemic rescue therapy prior to the post-vaccination vaccine response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemolizumab | Percentage of Participants With a Positive Serum Immunoglobulin G (IgG) Response (>= 4-Fold Increase or >= 0.2 IU/mL in Anti-Tetanus IgG Concentrations) to Tetanus Toxoid at Week 16 (4 Weeks Post-vaccination) | 67.5 Percentage of Participants |
| Placebo | Percentage of Participants With a Positive Serum Immunoglobulin G (IgG) Response (>= 4-Fold Increase or >= 0.2 IU/mL in Anti-Tetanus IgG Concentrations) to Tetanus Toxoid at Week 16 (4 Weeks Post-vaccination) | 65.4 Percentage of Participants |
90% CI: [-10.3, 14.5]
Secondary
Percentage of Participants With a Positive SBA Response (Defined as SBA Reciprocal Titer ≥8) to MenC Polysaccharide at Week 16
Percentage of participants with a positive SBA response to MenC polysaccharide, defined as SBA reciprocal titer \>= 8, at Week 16 were reported. Immune response to meningococcal vaccination was determined by measuring functional antibody responses using an SBA assay.
Time frame: At Week 16
Population: mITT population consisted of all randomized participants who received at least one dose of study drug and vaccine injection, had an evaluable vaccine response and did not receive any systemic rescue therapy prior to the post-vaccination vaccine response assessment. Here Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemolizumab | Percentage of Participants With a Positive SBA Response (Defined as SBA Reciprocal Titer ≥8) to MenC Polysaccharide at Week 16 | 83.3 Percentage of Participants |
| Placebo | Percentage of Participants With a Positive SBA Response (Defined as SBA Reciprocal Titer ≥8) to MenC Polysaccharide at Week 16 | 81.9 Percentage of Participants |
90% CI: [-9.3, 11.9]
Secondary
Percentage of Participants With a Positive Serum Bactericidal Antibody (SBA) Response to Meningococcal Serogroup C (MenC) Polysaccharide at Week 16
Percentage of participants with a positive SBA response to meningococcal serogroup C polysaccharide, defined as \>= 4-fold increase in SBA reciprocal titer from baseline (using non-imputed values), at Week 16 (4 weeks postvaccination) were reported.
Time frame: At Week 16
Population: mITT population consisted of all randomized participants who received at least one dose of study drug and vaccine injection, had an evaluable vaccine response and did not receive any systemic rescue therapy prior to the post-vaccination vaccine response assessment. Here Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemolizumab | Percentage of Participants With a Positive Serum Bactericidal Antibody (SBA) Response to Meningococcal Serogroup C (MenC) Polysaccharide at Week 16 | 77.0 Percentage of Participants |
| Placebo | Percentage of Participants With a Positive Serum Bactericidal Antibody (SBA) Response to Meningococcal Serogroup C (MenC) Polysaccharide at Week 16 | 63.6 Percentage of Participants |
90% CI: [0.1, 26.4]
Secondary
Percentage of Participants With a Positive Serum IgG Response (>=2-Fold Increase or >= 0.2 IU/mL in Anti-tetanus IgG Concentrations) to Tetanus Toxoid at Week 16 (4 Weeks Post-vaccination)
Percentage of participants with a positive serum IgG response to tetanus toxoid, defined as \>= 2-fold increase in anti-tetanus IgG concentrations from baseline in participants with pre-vaccination anti-tetanus IgG concentrations \>= 0.1 IU/mL; or \>= 0.2 IU/mL anti-tetanus IgG concentrations in participants with pre-vaccination Anti tetanus IgG concentrations \< 0.1 IU/mL, at Week 16 (4 weeks post-vaccination) were reported.
Time frame: At Week 16 (4 weeks post-vaccination)
Population: mITT population consisted of all randomized participants who received at least one dose of study drug and vaccine injection, had an evaluable vaccine response and did not receive any systemic rescue therapy prior to the post-vaccination vaccine response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemolizumab | Percentage of Participants With a Positive Serum IgG Response (>=2-Fold Increase or >= 0.2 IU/mL in Anti-tetanus IgG Concentrations) to Tetanus Toxoid at Week 16 (4 Weeks Post-vaccination) | 78.8 Percentage of Participants |
| Placebo | Percentage of Participants With a Positive Serum IgG Response (>=2-Fold Increase or >= 0.2 IU/mL in Anti-tetanus IgG Concentrations) to Tetanus Toxoid at Week 16 (4 Weeks Post-vaccination) | 83.3 Percentage of Participants |
90% CI: [-14.9, 5.7]
Secondary
Percentage of Participants With Serum Anti-tetanus IgG Concentrations of >= 0.1 IU/mL at Week 16
Percentage of participants with serum anti-tetanus IgG concentrations of \>= 0.1 IU/mL at Week 16 were reported. The detection and characterization of antibodies to tetanus toxoid was performed using a validated immunoassay.
Time frame: At Week 16
Population: mITT population consisted of all randomized participants who received at least one dose of study drug and vaccine injection, had an evaluable vaccine response and did not receive any systemic rescue therapy prior to the post-vaccination vaccine response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemolizumab | Percentage of Participants With Serum Anti-tetanus IgG Concentrations of >= 0.1 IU/mL at Week 16 | 100 Percentage of Participants |
| Placebo | Percentage of Participants With Serum Anti-tetanus IgG Concentrations of >= 0.1 IU/mL at Week 16 | 100 Percentage of Participants |
Secondary
Percentage of Participants With Serum Anti-tetanus IgG Concentrations of >= 1.0 IU/mL at Week 16
Percentage of participants with serum anti-tetanus IgG concentrations of \>= 1.0 IU/mL at Week 16 were reported. The detection and characterization of antibodies to tetanus toxoid was performed using a validated immunoassay.
Time frame: At Week 16
Population: mITT population consisted of all randomized participants who received at least one dose of study drug and vaccine injection, had an evaluable vaccine response and did not receive any systemic rescue therapy prior to the post-vaccination vaccine response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemolizumab | Percentage of Participants With Serum Anti-tetanus IgG Concentrations of >= 1.0 IU/mL at Week 16 | 97.5 Percentage of Participants |
| Placebo | Percentage of Participants With Serum Anti-tetanus IgG Concentrations of >= 1.0 IU/mL at Week 16 | 96.2 Percentage of Participants |
90% CI: [-3.2, 5.9]