Psoriasis
Conditions
Brief summary
The study will investigate the efficacy and safety compared to placebo and the safety compared to ustekinumab of brodalumab in adolescents with moderate to severe plaque psoriasis. The study will also investigate if brodalumab affects development of vaccination-induced immune responses. The study will run over 62-64 weeks (including screening, treatment, and safety follow-up) for each participant, but with the primary endpoint measured at Week 12.
Interventions
DRUGBrodalumab
Solution for subcutaneous injection.
DRUGUstekinumab
Solution for subcutaneous injection.
DRUGPlacebo
The placebo solution is similar to the active brodalumab solution except that it does not contain any active substance.
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind until Week 12, where the primary endpoint is assessed. Open-label active comparator treatment from Week 0 to Week 52, but with blinded outcomes assessor throughout the study.
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Subject was diagnosed with chronic plaque psoriasis at least 6 months before randomisation. * Subject has a diagnosis of moderate-to-severe plaque psoriasis as defined by PASI ≥12, sPGA ≥3, and body surface area ≥10% at screening and at baseline. * Subject, in whom topical therapy is not adequate, and who is a candidate for systemic therapy. * Subject has no evidence of active or latent tuberculosis according to local standard of care. Key
Exclusion criteria
* Subject is diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, or other skin conditions (e.g., eczema). * Subject has been vaccinated with a tetanus toxoid-containing vaccine ≤18 months prior to first dose of investigational medicinal product (IMP). For EU and UK: Subject has been vaccinated with a TT-containing vaccine within 5 years prior to the first dose of IMP. * Subject has developed or experienced either Guillian-Barre syndrome, encephalopathy, Arthus-type hypersensitivity, or severe allergic reactions in connection with previous Tdap or Td vaccine. * Subject with chronic or recurrent infections, or active infection, systemically treated within 4 weeks prior to first dose of IMP. * Subject has a known history of Crohn's disease. * Subject has any active malignancy or a history of any malignancy within 5 years. * Subject has a history of suicidal behaviour and has suicidal ideation with some intent to act or specific plan and intent. * Subject has a history of depressive disorder with severe episode(s) within the last 2 years. * Subject has received anti-IL-12/23p40 for less than 12 months prior to the first dose of IMP or has previously no response to anti-IL-12/23p40 therapy. * Subject has previously received anti-IL-17 therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Psoriasis Area and Severity Index (PASI) 75 Response, Assessed at Week 12. | Baseline to Week 12 | PASI 75 response is defined as having at least 75% improvement in PASI score from baseline. The severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, were assessed according to a severity scale. The extent of psoriasis within each of the 4 body regions was also assessed. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe and/or more extensive condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| sPGA Score of 0, Assessed at Week 12. | Week 12 | The sPGA is an instrument used in clinical trials to rate the severity of the participant's global psoriasis and is based on a 6-point scale ranging from 0 (clear) to 5 (very severe). The number of participants achieving a score of 0 (clear) or 1 (almost clear) was assessed. |
| PASI 90 Response, Assessed at Week 12. | Baseline to Week 12 | PASI 90 response is defined as having at least 90% improvement in PASI score from baseline. The severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, will be assessed according to a severity scale. The extent of psoriasis within each of the 4 body regions will also be assessed. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe and/or more extensive condition. |
| PASI 100 Response, Assessed at Week 12. | Baseline to Week 12 | PASI 100 response is defined as having at least 100% improvement in PASI score from baseline. The severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, will be assessed according to a severity scale. The extent of psoriasis within each of the 4 body regions will also be assessed. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe and/or more extensive condition. |
| Children's Dermatology Life Quality Index (CDLQI) Total Score of 0 or 1, Assessed at Week 12. | Week 12 | CDLQI consists of 10 items addressing the child's perception of the impact of their skin disease on various aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and the treatment. Each item is scored on a 4-point scale ranging from 0 (not at all) to 3 (very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality of life. |
| Family Dermatology Life Quality Index (FDLQI) Total Score of 0 or 1, Assessed at Week 12. | Week 12 | FDLQI consists of 10 items addressing the participant's relative perception of the impact of the participant's skin disease on various aspects of his/her quality of life over the last month such as: emotional distress, social life, job and leisure activities, physical well-being, time spent on helping the subject with e.g., treatment procedures, extra housework, and routine household expenditure. Each item is scored on a 4-point scale ranging from 0 (not at all) to 3 (very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality of life. |
| Static Physician's Global Assessment (sPGA) Score of 0 or 1, Assessed at Week 12. | Week 12 | The sPGA is an instrument used in clinical trials to rate the severity of the participant's global psoriasis and is based on a 6-point scale ranging from 0 (clear) to 5 (very severe). The number of participants achieving a score of 0 (clear) or 1 (almost clear) was assessed. |
| Presence of Anti-drug Antibodies, Assessed at Weeks 4, 16, and 52. | Week 4, Week 16, and Week 52 | Number of participants with a positive post-baseline anti-drug antibody result at weeks 4, 16, and 52. |
| Serum Concentration of Interleukin-17, Assessed at Weeks 8, 12, and 52. | Week 8, Week 12, and Week 52 | Number of participants with detectable levels of Interleukin-17 at weeks 8, 12, and 52. |
| Blood Levels of T-cell Subsets (CD4+ and CD8+), Assessed at Weeks 8, 12, and 52. | Week 8, Week 12, and Week 52 | Number of participants with detectable levels of T-cell subsets at weeks 8, 12, and 52. |
| Serum Concentrations of Brodalumab, Assessed at Weeks 4, 8, 10, 12, 16, 22, and 52. | Week 4, Week 8, Week 10, Week 12, Week 16, Week 22, and Week 52 | Number of participants with detectable levels of brodalumab at weeks 4, 8, 10, 12, 16, 22, and 52. |
| Anti-tetanus Toxoid Antibodies ≥0.1 IU/mL, Assessed at Week 12. | Week 12 | Number of participants with detectable levels of anti-tetanus toxoid antibodies at weeks 12. |
| Overall Number of Adverse Events (AEs) | Up to approximately 5 months | An AE is defined as any untoward medical occurrence in subjects or clinical investigation participants administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the patient or may require medical or surgical intervention to prevent any of the outcomes listed above. |
Countries
Belgium, France, Germany, Greece, Hungary, Italy, Poland, Spain
Participant flow
Recruitment details
Participants were recruited across countries in Europe (Belgium, Germany, Hungary, Italy, Poland, Spain) from December 2022 to May 2023 when the study was early terminated.
Pre-assignment details
In the 12 weeks Induction Period (Week 0 to Week 12) participants were assigned to brodalumab, ustekinumab or placebo. This was followed by a Maintenance Period of 40 weeks (Week 12 to Week 52) where those receiving ustekinumab or brodalumab continued with the same medication whereas participants on placebo were switched to either brodalumab or ustekinumab.
Participants by arm
| Arm | Count |
|---|---|
| Brodalumab Participants were randomised to receive brodalumab subcutaneously (SC) at Weeks 0, 1, 2, and then every 2 weeks until week 50. The dose was determined by the participant's body weight. Participants weighing 30 to \<70 kg received 140 mg brodalumab, participants weighing ≥70 kg received 210 mg brodalumab. Participants randomised at Week 0 to brodalumab would have continued with the allocated treatment until Week 52. | 0 |
| Ustekinumab Participants were randomised to receive ustekinumab SC at Week 0 and 4, and then every 12 weeks until Week 50. The dose was determined by the participant's body weight. Participants weighing 30 to \<60 kg received 0.75 mg ustekinumab per kg body weight. Participants weighing ≥60 and ≤100 kg received 45 mg ustekinumab, and those weighing \>100 kg received 90 mg ustekinumab. Participants randomised at Week 0 to ustekinumab would have continued with the allocated treatment until Week 52. | 0 |
| Placebo/Brodalumab Participants were randomised to receive placebo at Weeks 0, 1, 2, 4, 6, 8, and 10. Following the initial 12 Weeks of placebo, participants received brodalumab at Weeks 12, 13, 14, and every 2 weeks thereafter, with the last brodalumab dose administered at Week 50. The doses were body weight-dependent, participants weighing 30 to \<70 kg received 140 mg brodalumab or 1.0 mL placebo. Participants weighing ≥70 kg received 210 mg brodalumab or 1.5 mL placebo. | 0 |
| Placebo/Ustekinumab Participants were randomised to receive placebo at Weeks 0, 1, 2, 4, 6, 8, and 10. Following the initial 12 Weeks of placebo, participants received ustekimumab at Weeks 12, 16, 28, and 40. Doses of ustekimumab were body weight-dependent, participants weighing 30 to \<60 kg received 0.75 mg/kg. Participants weighing ≥60 and ≤100 kg received 45 mg ustekinumab, and those weighed \>100 kg received 90 mg ustekinumab. | 0 |
| Total | 0 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Study early termination | 2 | 5 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
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 / 2 | 0 / 6 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 2 / 2 | 3 / 6 | 0 / 2 | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 2 |
Outcome results
Primary
Psoriasis Area and Severity Index (PASI) 75 Response, Assessed at Week 12.
PASI 75 response is defined as having at least 75% improvement in PASI score from baseline. The severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, were assessed according to a severity scale. The extent of psoriasis within each of the 4 body regions was also assessed. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe and/or more extensive condition.
Time frame: Baseline to Week 12
Population: Participants who completed at Week 12 are included in the overall number of participants analysed. Dataset from the full analysis set (FAS) which includes all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brodalumab | Psoriasis Area and Severity Index (PASI) 75 Response, Assessed at Week 12. | NA Participants |
| Placebo/Ustekinumab | Psoriasis Area and Severity Index (PASI) 75 Response, Assessed at Week 12. | NA Participants |
Secondary
Anti-tetanus Toxoid Antibodies ≥0.1 IU/mL, Assessed at Week 12.
Number of participants with detectable levels of anti-tetanus toxoid antibodies at weeks 12.
Time frame: Week 12
Population: Due to early termination, data was not collected
Secondary
Blood Levels of T-cell Subsets (CD4+ and CD8+), Assessed at Weeks 8, 12, and 52.
Number of participants with detectable levels of T-cell subsets at weeks 8, 12, and 52.
Time frame: Week 8, Week 12, and Week 52
Population: Due to early termination, data was not collected
Secondary
Children's Dermatology Life Quality Index (CDLQI) Total Score of 0 or 1, Assessed at Week 12.
CDLQI consists of 10 items addressing the child's perception of the impact of their skin disease on various aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and the treatment. Each item is scored on a 4-point scale ranging from 0 (not at all) to 3 (very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality of life.
Time frame: Week 12
Population: Due to early termination, data was not collected
Secondary
Family Dermatology Life Quality Index (FDLQI) Total Score of 0 or 1, Assessed at Week 12.
FDLQI consists of 10 items addressing the participant's relative perception of the impact of the participant's skin disease on various aspects of his/her quality of life over the last month such as: emotional distress, social life, job and leisure activities, physical well-being, time spent on helping the subject with e.g., treatment procedures, extra housework, and routine household expenditure. Each item is scored on a 4-point scale ranging from 0 (not at all) to 3 (very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality of life.
Time frame: Week 12
Population: Due to early termination, data was not collected
Secondary
Overall Number of Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in subjects or clinical investigation participants administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the patient or may require medical or surgical intervention to prevent any of the outcomes listed above.
Time frame: Up to approximately 5 months
Population: Dataset from the safety analysis set (SAS) which includes all participants who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brodalumab | Overall Number of Adverse Events (AEs) | Any AEs | 4 Adverse events |
| Brodalumab | Overall Number of Adverse Events (AEs) | Any AEs related to IMP | 0 Adverse events |
| Ustekinumab | Overall Number of Adverse Events (AEs) | Any AEs related to IMP | 3 Adverse events |
| Ustekinumab | Overall Number of Adverse Events (AEs) | Any AEs | 5 Adverse events |
| Placebo/Brodalumab | Overall Number of Adverse Events (AEs) | Any AEs | 0 Adverse events |
| Placebo/Brodalumab | Overall Number of Adverse Events (AEs) | Any AEs related to IMP | 0 Adverse events |
| Placebo/Ustekinumab | Overall Number of Adverse Events (AEs) | Any AEs | 3 Adverse events |
| Placebo/Ustekinumab | Overall Number of Adverse Events (AEs) | Any AEs related to IMP | 0 Adverse events |
Secondary
PASI 100 Response, Assessed at Week 12.
PASI 100 response is defined as having at least 100% improvement in PASI score from baseline. The severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, will be assessed according to a severity scale. The extent of psoriasis within each of the 4 body regions will also be assessed. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe and/or more extensive condition.
Time frame: Baseline to Week 12
Population: Participants who completed at Week 12 are included in the overall number of participants analysed. Dataset from the FAS which includes all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brodalumab | PASI 100 Response, Assessed at Week 12. | NA Participants |
| Placebo/Ustekinumab | PASI 100 Response, Assessed at Week 12. | NA Participants |
Secondary
PASI 90 Response, Assessed at Week 12.
PASI 90 response is defined as having at least 90% improvement in PASI score from baseline. The severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, will be assessed according to a severity scale. The extent of psoriasis within each of the 4 body regions will also be assessed. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe and/or more extensive condition.
Time frame: Baseline to Week 12
Population: Participants who completed at Week 12 are included in the overall number of participants analysed. Dataset from the FAS which includes all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Brodalumab | PASI 90 Response, Assessed at Week 12. | NA Participants |
| Placebo/Ustekinumab | PASI 90 Response, Assessed at Week 12. | NA Participants |
Secondary
Presence of Anti-drug Antibodies, Assessed at Weeks 4, 16, and 52.
Number of participants with a positive post-baseline anti-drug antibody result at weeks 4, 16, and 52.
Time frame: Week 4, Week 16, and Week 52
Population: Due to early termination, data was not collected
Secondary
Serum Concentration of Interleukin-17, Assessed at Weeks 8, 12, and 52.
Number of participants with detectable levels of Interleukin-17 at weeks 8, 12, and 52.
Time frame: Week 8, Week 12, and Week 52
Population: Due to early termination, data was not collected
Secondary
Serum Concentrations of Brodalumab, Assessed at Weeks 4, 8, 10, 12, 16, 22, and 52.
Number of participants with detectable levels of brodalumab at weeks 4, 8, 10, 12, 16, 22, and 52.
Time frame: Week 4, Week 8, Week 10, Week 12, Week 16, Week 22, and Week 52
Population: Due to early termination, data was not collected
Secondary
sPGA Score of 0, Assessed at Week 12.
The sPGA is an instrument used in clinical trials to rate the severity of the participant's global psoriasis and is based on a 6-point scale ranging from 0 (clear) to 5 (very severe). The number of participants achieving a score of 0 (clear) or 1 (almost clear) was assessed.
Time frame: Week 12
Population: Due to early termination, data was not collected
Secondary
Static Physician's Global Assessment (sPGA) Score of 0 or 1, Assessed at Week 12.
The sPGA is an instrument used in clinical trials to rate the severity of the participant's global psoriasis and is based on a 6-point scale ranging from 0 (clear) to 5 (very severe). The number of participants achieving a score of 0 (clear) or 1 (almost clear) was assessed.
Time frame: Week 12
Population: Due to early termination, data was not collected