Atopic Dermatitis
Conditions
Keywords
Eczema, Dermatitis, Dermatitis, Atopic, Skin Diseases
Brief summary
This is designed to assess the long-term safety and efficacy of lebrikizumab for moderate-to-severe atopic dermatitis. It will last up to 33 months.
Detailed description
Participants who have completed participation in a Dermira- or Lilly-sponsored lebrikizumab study (parent study), DRM06-AD04 (NCT04146363), DRM06-AD05 (NCT04178967), DRM06-AD06 (NCT04250337), DRM06-AD17 (NCT04250350) or DRM06- AD18 (NCT04626297), will be offered the opportunity to enroll in this study. Participants may either be blinded or not blinded, depending on their parent study assignment. This study will also be open to an additional approximately 100 participants in the United States (addendum) who have not completed participation in a Dermira- or Lilly-sponsored lebrikizumab study. Treatment will not be blinded. This study will also include an Addendum to extend the study treatment period by an additional 32 weeks and to add a treatment arm testing dosing every 8 weeks. This Addendum will apply to existing study participants in selected countries. Treatment will not be blinded.
Interventions
BIOLOGICALLebrikizumab
Subcutaneous injection
Sponsors
Dermira, Inc.
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for participants coming from a parent study: Participants must meet all the following criteria to be eligible for this study: * Received treatment in a lebrikizumab study, NCT04146363, NCT04178967, NCT04250337, NCT04250350 and have adequately completed the study treatments and last patient visit of the parent trial. * For women of childbearing potential: agree to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method during the treatment period and for at least 18 weeks after the last dose of lebrikizumab or placebo.
Exclusion criteria
for participants coming from a parent study: Participants meeting any of the criteria below will not be included in this study: * Participants who, during their participation in the parent trial, developed a serious adverse event (SAE) deemed related to lebrikizumab, which in the opinion of the investigator or of the medical monitor could indicate that continued treatment with lebrikizumab may present an unreasonable risk for the participant. \* * Participants who, during their participation in the parent trial, developed an AE that was deemed related to lebrikizumab and led to study treatment discontinuation, which in the opinion of the investigator or of the medical monitor could indicate that continued treatment with lebrikizumab may present an unreasonable risk for the participant. \* * Conditions in the previous parent study consistent with protocol-defined criteria for permanent study drug discontinuation, if deemed related to lebrikizumab or led to investigator - or sponsor-initiated withdrawal of participant from the study (e.g., non-compliance, inability to complete study assessments, etc.). \* * Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study. Open-Label Addendum Inclusion Criteria: Participants must meet all the following criteria to be eligible for this study addendum: * Male or female adults and adolescents (≥12 to \<18 years of age and weighing ≥40 kilogram (kg). * Chronic AD (according to American Academy of Dermatology Consensus Criteria) that has been present for ≥1 year before screening. * Eczema Area and Severity Index (EASI) score ≥16 at baseline. * Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at baseline. * ≥10% body surface area (BSA) of AD involvement at baseline. * History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable. Open-Label Addendum
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Treatment Period: Percentage of Participants Discontinued From Study Treatment Due to Adverse Events | Baseline to Week 100 | Percentage of participants discontinued from study treatment due to adverse events is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Primary Treatment Period: Percentage of Participants With a Response of Investigator Global Assessment (IGA) Score 0 or 1 at Week 100 | Week 100 | The IGA measures the investigator's global assessment of the participant's overall severity of their Atopic Dermatitis. The IGA is comprised of a 5-point numeric scale ranging from 0 (clear skin) to 4 (severe disease) and a score is selected using descriptors that best describe the overall appearance of the lesions at a given time point. |
| Primary Treatment Period: Percentage of Participants Achieving Response of Eczema Area and Severity Index-75 (EASI-75) at Week 100 | Week 100 | EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs, by scoring the extent of disease (percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100%) and the severity of 4 clinical signs (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and neck, trunk, upper limbs, and lower limbs). Half scores are allowed. The final EASI score will be obtained by weight-averaging these 4 scores and will range from 0 to 72. A higher score represents greater disease severity. |
Countries
Australia, Bulgaria, Canada, Estonia, France, Germany, Latvia, Lithuania, Mexico, Poland, Singapore, South Korea, Spain, Taiwan, Ukraine, United States
Participant flow
Recruitment details
This study consists of 2 parts: * 100-week primary treatment period where participants were assigned to either Lebrikizumab Q4W or Q2W treatment arms. * 32-week open label extension addendum (Lebrikizumab Q4W and Lebrikizumab Q8W)
Participants by arm
| Arm | Count |
|---|---|
| Primary Treatment Period: Lebrikizumab Q4W 250 mg of Lebrikizumab, subcutaneous injection administered every 4 weeks (Q4W) up to 100 weeks. | 141 |
| Primary Treatment Period: Lebrikizumab Q2W 250 mg Lebrikizumab, subcutaneous injection administered every 2 weeks (Q2W) up to 100 weeks. | 1,012 |
| Total | 1,153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Open-Label Extension Addendum (32 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Open-Label Extension Addendum (32 Weeks) | Protocol Deviation | 0 | 0 | 1 | 0 |
| Open-Label Extension Addendum (32 Weeks) | Withdrawal by Subject | 0 | 0 | 0 | 1 |
| Primary Treatment Period (100 Weeks) | Adverse Event | 3 | 46 | 0 | 0 |
| Primary Treatment Period (100 Weeks) | Due to epidemic/pandemic | 0 | 1 | 0 | 0 |
| Primary Treatment Period (100 Weeks) | Geopolitical conflict | 1 | 1 | 0 | 0 |
| Primary Treatment Period (100 Weeks) | Lack of Efficacy | 1 | 47 | 0 | 0 |
| Primary Treatment Period (100 Weeks) | Lost to Follow-up | 11 | 61 | 0 | 0 |
| Primary Treatment Period (100 Weeks) | Physician Decision | 1 | 5 | 0 | 0 |
| Primary Treatment Period (100 Weeks) | Pregnancy | 1 | 8 | 0 | 0 |
| Primary Treatment Period (100 Weeks) | Protocol deviation | 1 | 12 | 0 | 0 |
| Primary Treatment Period (100 Weeks) | Site Closure | 0 | 4 | 0 | 0 |
| Primary Treatment Period (100 Weeks) | Sponsor Decision | 1 | 14 | 0 | 0 |
| Primary Treatment Period (100 Weeks) | Withdrawal by Subject | 18 | 138 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Primary Treatment Period: Lebrikizumab Q2W | Primary Treatment Period: Lebrikizumab Q4W |
|---|---|---|---|
| Age, Continuous | 32.8 years STANDARD_DEVIATION 17.21 | 32.5 years STANDARD_DEVIATION 17.23 | 34.9 years STANDARD_DEVIATION 16.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 17 Participants | 16 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 220 Participants | 199 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 147 Participants | 138 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 28 Participants | 25 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 10 Participants | 9 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants | 15 Participants | 0 Participants |
| Race (NIH/OMB) White | 716 Participants | 610 Participants | 106 Participants |
| Region of Enrollment Australia | 26 Participants | 23 Participants | 3 Participants |
| Region of Enrollment Bulgaria | 10 Participants | 10 Participants | 0 Participants |
| Region of Enrollment Canada | 94 Participants | 80 Participants | 14 Participants |
| Region of Enrollment Estonia | 5 Participants | 5 Participants | 0 Participants |
| Region of Enrollment France | 4 Participants | 3 Participants | 1 Participants |
| Region of Enrollment Germany | 62 Participants | 52 Participants | 10 Participants |
| Region of Enrollment Latvia | 8 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Lithuania | 13 Participants | 12 Participants | 1 Participants |
| Region of Enrollment Mexico | 4 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Poland | 158 Participants | 135 Participants | 23 Participants |
| Region of Enrollment Singapore | 8 Participants | 7 Participants | 1 Participants |
| Region of Enrollment South Korea | 27 Participants | 25 Participants | 2 Participants |
| Region of Enrollment Spain | 7 Participants | 7 Participants | 0 Participants |
| Region of Enrollment Taiwan | 55 Participants | 51 Participants | 4 Participants |
| Region of Enrollment Ukraine | 9 Participants | 4 Participants | 5 Participants |
| Region of Enrollment United States | 663 Participants | 591 Participants | 72 Participants |
| Sex: Female, Male Female | 595 Participants | 513 Participants | 82 Participants |
| Sex: Female, Male Male | 558 Participants | 499 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 141 | 2 / 1,012 | 0 / 52 | 0 / 51 |
| other Total, other adverse events | 89 / 141 | 638 / 1,012 | 17 / 52 | 13 / 51 |
| serious Total, serious adverse events | 5 / 141 | 45 / 1,012 | 0 / 52 | 0 / 51 |
Outcome results
Primary
Primary Treatment Period: Percentage of Participants Discontinued From Study Treatment Due to Adverse Events
Percentage of participants discontinued from study treatment due to adverse events is reported.
Time frame: Baseline to Week 100
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Treatment Period: Lebrikizumab Q4W | Primary Treatment Period: Percentage of Participants Discontinued From Study Treatment Due to Adverse Events | 2.1 percentage of participants |
| Primary Treatment Period: Lebrikizumab Q2W | Primary Treatment Period: Percentage of Participants Discontinued From Study Treatment Due to Adverse Events | 4.5 percentage of participants |
Secondary
Primary Treatment Period: Percentage of Participants Achieving Response of Eczema Area and Severity Index-75 (EASI-75) at Week 100
EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs, by scoring the extent of disease (percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100%) and the severity of 4 clinical signs (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and neck, trunk, upper limbs, and lower limbs). Half scores are allowed. The final EASI score will be obtained by weight-averaging these 4 scores and will range from 0 to 72. A higher score represents greater disease severity.
Time frame: Week 100
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Treatment Period: Lebrikizumab Q4W | Primary Treatment Period: Percentage of Participants Achieving Response of Eczema Area and Severity Index-75 (EASI-75) at Week 100 | 90.4 Percentage of participants |
| Primary Treatment Period: Lebrikizumab Q2W | Primary Treatment Period: Percentage of Participants Achieving Response of Eczema Area and Severity Index-75 (EASI-75) at Week 100 | 79.4 Percentage of participants |
Secondary
Primary Treatment Period: Percentage of Participants With a Response of Investigator Global Assessment (IGA) Score 0 or 1 at Week 100
The IGA measures the investigator's global assessment of the participant's overall severity of their Atopic Dermatitis. The IGA is comprised of a 5-point numeric scale ranging from 0 (clear skin) to 4 (severe disease) and a score is selected using descriptors that best describe the overall appearance of the lesions at a given time point.
Time frame: Week 100
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Treatment Period: Lebrikizumab Q4W | Primary Treatment Period: Percentage of Participants With a Response of Investigator Global Assessment (IGA) Score 0 or 1 at Week 100 | 80.1 Percentage of participants |
| Primary Treatment Period: Lebrikizumab Q2W | Primary Treatment Period: Percentage of Participants With a Response of Investigator Global Assessment (IGA) Score 0 or 1 at Week 100 | 60.6 Percentage of participants |