Acneiform Eruptions
Conditions
Keywords
IL-36 receptor, Interleukin 36, Imsidolimab
Brief summary
Efficacy and Safety of imsidolimab in participants with epidermal growth factor receptor inhibitor (EGFRi)/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase inhibitor (MEKi)-associated acneiform Rash
Detailed description
This study is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of imsidolimab compared with placebo in cancer participants with EGFRi/MEKi-associated acneiform rash. This study will also characterize the pharmacokinetic (PK) profile of imsidolimab and explore the immune response to imsidolimab in participants with EGFRi/MEKi-associated acneiform rash.
Interventions
BIOLOGICALImsidolimab
Humanized monoclonal antibody
BIOLOGICALPlacebo
Placebo
Sponsors
Vanda Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participant has cancer * Participant is treated with an oral or injectable Food and Drug Administration (FDA)-approved EGFRi or MEKi therapy * Participant has EGFRi/MEKi-related acneiform rash of Grade ≥ 2 as per common terminology criteria for adverse events (CTCAE) version 5.0, and ≥ 20 inflammatory lesions on the face at screening and Day 1.
Exclusion criteria
* Participant has infected EGFRi/MEKi-associated acneiform rash according to investigator's evaluation. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Facial Inflammatory Lesion Count (Papules and Pustules) at Week 8 | Baseline, Week 8 | The number of facial inflammatory lesions (papules and pustules) on the face (excluding the neck and scalp area) was counted. Papule was a small, solid elevation 5 millimeters (mm) or less in diameter. Pastule was a small, circumscribed elevation of the skin that contains yellow-white exudate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Improvement of at Least 1 Grade From Baseline in Acneiform Rash Common Terminology Criteria for Adverse Events (CTCAE) Grading Scale at Week 8 | Baseline, Week 8 | The acneiform rash CTCAE grading scale of severity was 6-point scale ranging from 0-5. Scale 0=no evidence of rash. Scale 1= papules and/or pustules covering \<10% body surface area (BSA), which may or may not be associated with symptoms of pruritus or tenderness. Scale 2=papules and/or pustules covering 10-30% BSA, which may or may not be associated with symptoms of pruritus or tenderness; associated with psychosocial impact; limiting instrumental activities of daily living (ADL); papules and/or pustules covering \>30% BSA with or without mild symptoms. Scale 3=papules and/or pustules covering \>30% BSA with moderate or severe symptoms; limiting self-care ADL; associated with local superinfection with oral antibiotics. Scale 4=life-threatening consequences; papules and/or pustules covering any %BSA, which may or may not be associated with symptoms of pruritus or tenderness and are associated with extensive superinfection with intravenous (IV) antibiotics indicated. Scale 5=death. |
| Time to First Response of 1 Grade Improvement From Baseline on the Acneiform Rash CTCAE Grading Scale | Baseline up to 55 days | Time to first response of 1 grade improvement from baseline on the acneiform rash CTCAE grading scale: Date of the first response of 1 grade improvement from baseline on the acneiform rash CTCAE grading scale - Date of the first dose of study treatment (or from randomization for any participant randomized but not treated) + 1. |
| Percentage of Participants With an Improvement of at Least 1 Grade From Baseline in Acneiform Rash Modified Multinational Association for Supportive Care in Cancer (MASCC) EGFRi Skin Toxicity Tool (MESTT) Grading Scale (Total Score) at Week 8 | Baseline, Week 8 | The MESTT grading scale of the acneiform rash severity was a 3-point scale ranging from 1 to 3: Scale 1 = 1A: papules or pustules ≤5; OR 1 area of erythema or edema \<1 centimeter (cm) in size. 1B: papules or pustules ≤5; OR 1 area of erythema or edema \<1 cm in size; AND pain or pruritus. Scale 2 = 2A: papules or pustules 6-20; OR 2-5 areas of erythema or edema \<1 cm in size. 2B: Papules or pustules 6-20; OR 2-5 areas of erythema or edema \<1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Scale 3 = 3A: papules or pustules \> 20; OR more than 5 areas of erythema or edema \<1 cm in size. 3B: papules or pustules \> 20; OR more than 5 areas of erythema or edema \<1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Grading was performed individually for the face, scalp, chest, and back. The sum of all body region scores yielded the total score (range: 4 to 12). |
| Time to First Response of 1 Grade Improvement From Baseline on the Acneiform Rash Modified MESTT Grading Scale (Total Score) | Baseline to 55 days | Time to first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (total score): Date of onset of the first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (total score) - Date of the first dose of study treatment (or from randomization for any participant randomized but not treated) + 1. |
| Percentage of Participants With an Improvement of at Least 1 Grade From Baseline in Acneiform Rash Modified MESTT Grading Scale (Facial Assessment) at Week 8 | Baseline, Week 8 | The MESTT grading scale of the acneiform rash severity was a 3-point scale ranging from 1 to 3: Scale 1 = 1A: papules or pustules ≤5; OR 1 area of erythema or edema \<1cm in size. 1B: papules or pustules ≤5; OR 1 area of erythema or edema \<1 cm in size; AND pain or pruritus. Scale 2 = 2A: papules or pustules 6-20; OR 2-5 areas of erythema or edema \<1 cm in size. 2B: Papules or pustules 6-20; OR 2-5 areas of erythema or edema \<1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Scale 3 = 3A: papules or pustules \> 20; OR more than 5 areas of erythema or edema \<1 cm in size. 3B: papules or pustules \> 20; OR more than 5 areas of erythema or edema \<1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Grading was performed individually for the face. The score ranged from 1 to 3. |
| Time to First Response of 1 Grade Improvement From Baseline on the Acneiform Rash Modified MESTT Grading Scale (Facial Assessment) | Baseline to 55 days | Time to first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (facial assessment): Date of onset of the first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (facial assessment) - Date of the first dose of study treatment (or from randomization for any participant randomized but not treated) + 1. |
| Percent Change From Baseline in Facial Inflammatory Lesion Count (Papules and Pustules) at Week 8 | Baseline, Week 8 | The number of facial inflammatory lesions (papules and pustules) on the face (excluding the neck and scalp area) was counted. Papule was a small, solid elevation 5 mm or less in diameter. Pastule was a small, circumscribed elevation of the skin that contains yellow-white exudate. |
| Percent Change From Baseline in Pruritus NRS at Week 8 | Baseline, Week 8 | The intensity of pruritus was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no itch and 10 indicating the worst imaginable itch. |
| Change From Baseline in Pain NRS at Week 8 | Baseline, Week 8 | The intensity of pain was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no pain and 10 indicating the worst imaginable pain. |
| Percent Change From Baseline in Pain NRS at Week 8 | Baseline, Week 8 | The intensity of pain was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no pain and 10 indicating the worst imaginable pain. |
| Change From Baseline in Functional Assessment of Cancer Therapy - Epidermal Growth Factor Receptor Inhibitor 18 (FACT-EGFRi-18) at Week 8 | Baseline, Week 8 | The FACT-EGFRi-18 was an 18-item likert-scaled questionnaire, arranged in three dimensions: physical (seven items), social/emotional (six items), and functional well-being (five items). The response scores ranged from 0 (not at all) to 4 (very much). The total score was obtained by multiplying the sum of the subscale by the number of items in the scale (18), and then dividing by the number of items actually answered. The total score ranged from 0-72 with a higher score represented a high level of symptomatology (problems). |
| Number of Participants With Treatment-Emergent Adverse Events | From first dose to 55 days | An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of a study treatment, whether or not considered related to study treatment. An AE could therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of study treatment that did not necessarily have a causal relationship with this treatment. An AE was considered serious if there was any of the following outcomes: death, life-threatening, Inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of ability to conduct normal life functions, congenital anomaly/birth defect, other important medical events. An AE was considered treatment-emergent if the date of onset was during or after first dose of study treatment, or if the AE present at baseline worsened in either intensity or frequency after first dose of study treatment. |
| Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 8 | Baseline, Week 8 | The intensity of pruritus was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no itch and 10 indicating the worst imaginable itch. |
Countries
Czechia, Georgia, Latvia, Poland, United States
Participant flow
Recruitment details
Participants with neoplasms who were receiving epidermal growth factor inhibitors or mitogen-activated protein/extracellular signal regulated kinase inhibitor were enrolled into the study.
Pre-assignment details
11 participants were screened for eligibility and 4 participants were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Imsidolimab Participants received a starting dose of 400 mg of imsidolimab on Day 1 followed by 200 mg imsidolimab every 4 weeks (Days 29, 57 and 85) by subcutaneous injection. | 2 |
| Placebo Participants received imsidolimab matching placebo on Day 1 and thereafter, every 4 weeks (Days 29, 57 and 85) by subcutaneous injection. | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study termination | 2 | 1 |
| Overall Study | Withdrew consent due to possible/perceived lack of efficacy by participants | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Imsidolimab |
|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 2.83 | 57.5 years STANDARD_DEVIATION 10.5 | 50.0 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 0 / 2 | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
Change From Baseline in Facial Inflammatory Lesion Count (Papules and Pustules) at Week 8
The number of facial inflammatory lesions (papules and pustules) on the face (excluding the neck and scalp area) was counted. Papule was a small, solid elevation 5 millimeters (mm) or less in diameter. Pastule was a small, circumscribed elevation of the skin that contains yellow-white exudate.
Time frame: Baseline, Week 8
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy - Epidermal Growth Factor Receptor Inhibitor 18 (FACT-EGFRi-18) at Week 8
The FACT-EGFRi-18 was an 18-item likert-scaled questionnaire, arranged in three dimensions: physical (seven items), social/emotional (six items), and functional well-being (five items). The response scores ranged from 0 (not at all) to 4 (very much). The total score was obtained by multiplying the sum of the subscale by the number of items in the scale (18), and then dividing by the number of items actually answered. The total score ranged from 0-72 with a higher score represented a high level of symptomatology (problems).
Time frame: Baseline, Week 8
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Change From Baseline in Pain NRS at Week 8
The intensity of pain was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no pain and 10 indicating the worst imaginable pain.
Time frame: Baseline, Week 8
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 8
The intensity of pruritus was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no itch and 10 indicating the worst imaginable itch.
Time frame: Baseline, Week 8
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Number of Participants With Treatment-Emergent Adverse Events
An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of a study treatment, whether or not considered related to study treatment. An AE could therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of study treatment that did not necessarily have a causal relationship with this treatment. An AE was considered serious if there was any of the following outcomes: death, life-threatening, Inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of ability to conduct normal life functions, congenital anomaly/birth defect, other important medical events. An AE was considered treatment-emergent if the date of onset was during or after first dose of study treatment, or if the AE present at baseline worsened in either intensity or frequency after first dose of study treatment.
Time frame: From first dose to 55 days
Population: Safety analysis set included all randomized participants who received at least 1 dose of imsidolimab or placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Imsidolimab | Number of Participants With Treatment-Emergent Adverse Events | Any TEAEs | 0 Participants |
| Imsidolimab | Number of Participants With Treatment-Emergent Adverse Events | Serious TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Any TEAEs | 2 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events | Serious TEAEs | 0 Participants |
Secondary
Percentage of Participants With an Improvement of at Least 1 Grade From Baseline in Acneiform Rash Common Terminology Criteria for Adverse Events (CTCAE) Grading Scale at Week 8
The acneiform rash CTCAE grading scale of severity was 6-point scale ranging from 0-5. Scale 0=no evidence of rash. Scale 1= papules and/or pustules covering \<10% body surface area (BSA), which may or may not be associated with symptoms of pruritus or tenderness. Scale 2=papules and/or pustules covering 10-30% BSA, which may or may not be associated with symptoms of pruritus or tenderness; associated with psychosocial impact; limiting instrumental activities of daily living (ADL); papules and/or pustules covering \>30% BSA with or without mild symptoms. Scale 3=papules and/or pustules covering \>30% BSA with moderate or severe symptoms; limiting self-care ADL; associated with local superinfection with oral antibiotics. Scale 4=life-threatening consequences; papules and/or pustules covering any %BSA, which may or may not be associated with symptoms of pruritus or tenderness and are associated with extensive superinfection with intravenous (IV) antibiotics indicated. Scale 5=death.
Time frame: Baseline, Week 8
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Percentage of Participants With an Improvement of at Least 1 Grade From Baseline in Acneiform Rash Modified MESTT Grading Scale (Facial Assessment) at Week 8
The MESTT grading scale of the acneiform rash severity was a 3-point scale ranging from 1 to 3: Scale 1 = 1A: papules or pustules ≤5; OR 1 area of erythema or edema \<1cm in size. 1B: papules or pustules ≤5; OR 1 area of erythema or edema \<1 cm in size; AND pain or pruritus. Scale 2 = 2A: papules or pustules 6-20; OR 2-5 areas of erythema or edema \<1 cm in size. 2B: Papules or pustules 6-20; OR 2-5 areas of erythema or edema \<1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Scale 3 = 3A: papules or pustules \> 20; OR more than 5 areas of erythema or edema \<1 cm in size. 3B: papules or pustules \> 20; OR more than 5 areas of erythema or edema \<1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Grading was performed individually for the face. The score ranged from 1 to 3.
Time frame: Baseline, Week 8
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Percentage of Participants With an Improvement of at Least 1 Grade From Baseline in Acneiform Rash Modified Multinational Association for Supportive Care in Cancer (MASCC) EGFRi Skin Toxicity Tool (MESTT) Grading Scale (Total Score) at Week 8
The MESTT grading scale of the acneiform rash severity was a 3-point scale ranging from 1 to 3: Scale 1 = 1A: papules or pustules ≤5; OR 1 area of erythema or edema \<1 centimeter (cm) in size. 1B: papules or pustules ≤5; OR 1 area of erythema or edema \<1 cm in size; AND pain or pruritus. Scale 2 = 2A: papules or pustules 6-20; OR 2-5 areas of erythema or edema \<1 cm in size. 2B: Papules or pustules 6-20; OR 2-5 areas of erythema or edema \<1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Scale 3 = 3A: papules or pustules \> 20; OR more than 5 areas of erythema or edema \<1 cm in size. 3B: papules or pustules \> 20; OR more than 5 areas of erythema or edema \<1 cm in size; AND pain, pruritus, or effect on emotions or functioning. Grading was performed individually for the face, scalp, chest, and back. The sum of all body region scores yielded the total score (range: 4 to 12).
Time frame: Baseline, Week 8
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Percent Change From Baseline in Facial Inflammatory Lesion Count (Papules and Pustules) at Week 8
The number of facial inflammatory lesions (papules and pustules) on the face (excluding the neck and scalp area) was counted. Papule was a small, solid elevation 5 mm or less in diameter. Pastule was a small, circumscribed elevation of the skin that contains yellow-white exudate.
Time frame: Baseline, Week 8
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Percent Change From Baseline in Pain NRS at Week 8
The intensity of pain was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no pain and 10 indicating the worst imaginable pain.
Time frame: Baseline, Week 8
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Percent Change From Baseline in Pruritus NRS at Week 8
The intensity of pruritus was evaluated by asking participants to assign a numerical score representing the worst intensity over the last 24 hours of their symptoms on a scale from 0 to 10, with 0 indicating no itch and 10 indicating the worst imaginable itch.
Time frame: Baseline, Week 8
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Time to First Response of 1 Grade Improvement From Baseline on the Acneiform Rash CTCAE Grading Scale
Time to first response of 1 grade improvement from baseline on the acneiform rash CTCAE grading scale: Date of the first response of 1 grade improvement from baseline on the acneiform rash CTCAE grading scale - Date of the first dose of study treatment (or from randomization for any participant randomized but not treated) + 1.
Time frame: Baseline up to 55 days
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Time to First Response of 1 Grade Improvement From Baseline on the Acneiform Rash Modified MESTT Grading Scale (Facial Assessment)
Time to first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (facial assessment): Date of onset of the first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (facial assessment) - Date of the first dose of study treatment (or from randomization for any participant randomized but not treated) + 1.
Time frame: Baseline to 55 days
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.
Secondary
Time to First Response of 1 Grade Improvement From Baseline on the Acneiform Rash Modified MESTT Grading Scale (Total Score)
Time to first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (total score): Date of onset of the first response of 1 grade improvement from baseline on the acneiform rash modified MESTT grading scale (total score) - Date of the first dose of study treatment (or from randomization for any participant randomized but not treated) + 1.
Time frame: Baseline to 55 days
Population: Due to early study termination, no participant was evaluated in the imsidolimab group and 1 participant was evaluated in the placebo group. Since only 1 participant was evaluated, results were not reported for the protection of personal data and to avoid re-identification.