Atopic Dermatitis
Conditions
Brief summary
The purpose of this extension trial is to evaluate the long-term safety of tralokinumab.
Interventions
DRUGTralokinumab
Human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. Presented as a liquid formulation for subcutaneous injection.
Sponsors
LEO Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completed the treatment period(s) of one of the parent trials: LP0162-1325, -1326, -1334, -1339, -1341, -1342, -1343, -1346, or TRA-WEI-0015-I. * Complied with the clinical trial protocol in the parent trial to the satisfaction of the investigator. * Able and willing to self-administer tralokinumab treatment (or have it administered by a caregiver) at home after the initial 3 injection visits at the trial site (in this trial). * Stable dose of emollient twice daily (or more, as needed) for at least 14 days before baseline.
Exclusion criteria
* Any condition that required permanent discontinuation of trial treatment in the parent trial. * More than 26 weeks have elapsed since the subject received the last injection of investigational medicinal product (IMP) in the parent trial (to be assessed at baseline). * Subjects who, during their participation in the parent trial, developed a serious adverse event (SAE) deemed related to tralokinumab by the investigator, which in the opinion of the investigator could indicate that continued treatment with tralokinumab may present an unreasonable safety risk for the subject. * Subjects who, during their participation in the parent trial, developed an AE that was deemed related to tralokinumab by the investigator and led to temporary discontinuation of trial treatment, which in the opinion of the investigator could indicate that continued treatment with tralokinumab may present an unreasonable safety risk for the subject. * Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 4 weeks prior to baseline. * Treatment with topical phosphodiesterase 4 inhibitors or topical JAK inhibitors within 2 weeks prior to baseline. * Clinically significant infection within 4 weeks prior to baseline. * A helminth parasitic infection within 6 months prior to the date when informed consent is obtained. * Tuberculosis requiring treatment within 12 months prior to screening. * Known primary immunodeficiency disorder.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Adverse Events From Baseline Through the Last Treatment Visit (up to Week 268) | From Week 0 up to Week 268 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | From Week 16 up to Week 248 | The IGA is an instrument used in clinical trials to rate the severity of the subject's global atopic dermatitis and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). |
| At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | From Week 16 up to Week 248 | The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of atopic dermatitis. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe or more extensive condition. |
Countries
Belgium, Canada, Czechia, France, Germany, Italy, Japan, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
This trial was conducted at 309 sites that screened subjects in 11 countries.
Participants by arm
| Arm | Count |
|---|---|
| Tralokinumab, All Subjects Week 0: subcutaneous (SC) injection of tralokinumab loading dose.
From Week 2 up to Week 266\*: SC injection of tralokinumab maintenance dose.
\*The length of treatment for each subject will depend on when they enter the trial, and on which parent trial and country they come from.
Tralokinumab: Human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. Presented as a liquid formulation for subcutaneous injection. | 1,672 |
| Total | 1,672 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 72 |
| Overall Study | COVID_19 pandemic | 4 |
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 119 |
| Overall Study | Lost to Follow-up | 78 |
| Overall Study | Reason unknown | 26 |
| Overall Study | Various reasons | 121 |
| Overall Study | Withdrawal by parent/guardian | 3 |
| Overall Study | Withdrawal by Subject | 105 |
Baseline characteristics
| Characteristic | Tralokinumab, All Subjects |
|---|---|
| Age, Categorical <=18 years | 103 Participants |
| Age, Categorical >=65 years | 71 Participants |
| Age, Categorical Between 18 and 65 years | 1498 Participants |
| Age, Continuous | 37.5 years STANDARD_DEVIATION 14.8 |
| BMI (kg/m^2) | 26.52 kg/m^2 STANDARD_DEVIATION 6.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 112 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1558 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Height (cm) | 170.3 cm STANDARD_DEVIATION 10.1 |
| Race/Ethnicity, Customized American indian or alaska native | 2 Participants |
| Race/Ethnicity, Customized Asian | 312 Participants |
| Race/Ethnicity, Customized Black or african american | 120 Participants |
| Race/Ethnicity, Customized Missing | 2 Participants |
| Race/Ethnicity, Customized Native hawaiian or other pacific islander | 4 Participants |
| Race/Ethnicity, Customized Other | 38 Participants |
| Race/Ethnicity, Customized White | 1194 Participants |
| Region of Enrollment Belgium | 69 participants |
| Region of Enrollment Canada | 237 participants |
| Region of Enrollment Czechia | 20 participants |
| Region of Enrollment France | 73 participants |
| Region of Enrollment Germany | 268 participants |
| Region of Enrollment Italy | 15 participants |
| Region of Enrollment Japan | 181 participants |
| Region of Enrollment Poland | 228 participants |
| Region of Enrollment Spain | 127 participants |
| Region of Enrollment United Kingdom | 70 participants |
| Region of Enrollment United States | 384 participants |
| Sex: Female, Male Female | 709 Participants |
| Sex: Female, Male Male | 963 Participants |
| Weight (kg) | 77.1 Kg STANDARD_DEVIATION 19.1 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1,672 |
| other Total, other adverse events | 924 / 1,672 |
| serious Total, serious adverse events | 151 / 1,672 |
Outcome results
Primary
Number of Adverse Events From Baseline Through the Last Treatment Visit (up to Week 268)
Time frame: From Week 0 up to Week 268
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tralokinumab, All Subjects | Number of Adverse Events From Baseline Through the Last Treatment Visit (up to Week 268) | 8119 events |
Secondary
At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248
The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of atopic dermatitis. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe or more extensive condition.
Time frame: From Week 16 up to Week 248
Population: Modified non-responder analysis with data multiply imputed using a hypothetical strategy. Response is based on observed and multiply imputed data. If a participant permanently discontinued IMP due to lack of efficacy or adverse event before the analyzed visit, they are considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tralokinumab, All Subjects | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | EASI75 at Week 16 | 77.0 percentage of responders |
| Tralokinumab, All Subjects | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | EASI75 at Week 104 | 74.6 percentage of responders |
| Tralokinumab, All Subjects | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | EASI75 at Week 136 | 74.1 percentage of responders |
| Tralokinumab, All Subjects | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | EASI75 at Week 152 | 73.0 percentage of responders |
| Tralokinumab, All Subjects | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | EASI75 at Week 184 | 72.3 percentage of responders |
| Tralokinumab, All Subjects | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | EASI75 at Week 216 | 72.1 percentage of responders |
| Tralokinumab, All Subjects | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | EASI75 at Week 248 | 71.7 percentage of responders |
| Tralokinumab, All Subjects | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | EASI75 at Week 56 | 75.2 percentage of responders |
| Tralokinumab, All Subjects | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) Relative to Baseline in Parent Trial, at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | EASI75 at Week 88 | 75.1 percentage of responders |
Secondary
Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248
The IGA is an instrument used in clinical trials to rate the severity of the subject's global atopic dermatitis and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Time frame: From Week 16 up to Week 248
Population: Modified non-responder analysis with data multiply imputed using a hypothetical strategy. Response is based on observed and multiply imputed data. If a participant permanently discontinued IMP due to lack of efficacy or adverse event before the analyzed visit, they are considered non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tralokinumab, All Subjects | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | IGA 0/1 at Week 88 | 48.6 percentage of responders |
| Tralokinumab, All Subjects | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | IGA 0/1 at Week 104 | 47.1 percentage of responders |
| Tralokinumab, All Subjects | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | IGA 0/1 at Week 136 | 48.7 percentage of responders |
| Tralokinumab, All Subjects | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | IGA 0/1 at Week 152 | 46.8 percentage of responders |
| Tralokinumab, All Subjects | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | IGA 0/1 at Week 248 | 46.9 percentage of responders |
| Tralokinumab, All Subjects | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | IGA 0/1 at Week 16 | 47.3 percentage of responders |
| Tralokinumab, All Subjects | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | IGA 0/1 at Week 56 | 48.5 percentage of responders |
| Tralokinumab, All Subjects | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | IGA 0/1 at Week 184 | 46.7 percentage of responders |
| Tralokinumab, All Subjects | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Weeks 16, 56, 88, 104, 136, 152, 184, 216, and 248 | IGA 0/1 at Week 216 | 47.2 percentage of responders |