Ichthyosis
Conditions
Keywords
IL-36 Receptor, Interleukin 36, Imsidolimab
Brief summary
Efficacy and Safety of imsidolimab in Participants with Ichthyosis
Detailed description
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of imsidolimab compared with placebo in adolescent and adult participants with ichthyosis. This study will also characterize the pharmacokinetic (PK) profile of imsidolimab and explore the immune response to imsidolimab in participants with ichthyosis.
Interventions
DRUGImsidolimab
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)
Masking description
double blind
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Ichthyosis * IASI total score ≥ 18, erythema score ≥ 2 * Participant has been using emollient daily for at least 1 week prior to Day 1 and agrees to continue using that same emollient daily at the same frequency throughout the study
Exclusion criteria
* A participant with ichthyosis vulgaris, X-linked ichthyosis, or lamellar ichthyosis will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Ichthyosis Area Severity Index (IASI) Total Score at Week 16 | Baseline and Week 16 | IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling & percentage of body surface area (BSA) affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 body regions (BR) \[A1: head & neck (H&N), A2: upper limbs (UL), A3: trunk (T), A4: lower limbs (LL)\]. Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value(0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6).Total extent was determined using multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-Erythema (E)= A1E x B1 x C1 + A2E x B2 x C2 + A3E x B3 x C3 + A4E x B4 x C4 (score 0 to 24) IASI-Scaling (S)= A1S x B1 X C1 + A2S x B2 x C2 + A3S x B3 x C3 + A4S x B4 x C4 (score 0 to 24) IASI total score= IASI-E + IASI-S score ranged from 0 - 48, higher score indicated worse disease state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving an Improvement of 50% From Baseline in IASI (IASI50) at Week 16 | Week 16 | IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-E= A1E x B1 x C1 + A2E x B2 x C2 + A3E x B3 x C3 + A4E x B4 x C4 (score 0 to 24) IASI-S= A1S x B1 X C1 + A2S x B2 x C2 + A3S x B3 x C3 + A4S x B4 x C4 (score 0 to 24) IASI total score= IASI-E + IASI-S score ranged from 0 - 48, higher score indicated worse disease state. |
| Change From Baseline in IASI-E Scores at Week 16 | Baseline and Week 16 | IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-E= A1E x B1 x C1 + A2E x B2 x C2 + A3E x B3 x C3 + A4E x B4 x C4 IASI-E score ranged from 0 - 24, higher score indicated worse disease state. |
| Change From Baseline in IASI-S Scores at Week 16 | Baseline and Week 16 | IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-S= A1S x B1 X C1 + A2S x B2 x C2 + A3S x B3 x C3 + A4S x B4 x C4 IASI-S score ranged from 0 - 24, higher score indicated worse disease state. |
| Percent Change From Baseline in IASI Total Score at Week 16 | Baseline and Week 16 | IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-E= A1E x B1 x C1 + A2E x B2 x C2 + A3E x B3 x C3 + A4E x B4 x C4 (score 0 to 24) IASI-S= A1S x B1 X C1 + A2S x B2 x C2 + A3S x B3 x C3 + A4S x B4 x C4 (score 0 to 24) IASI total score= IASI-E + IASI-S score ranged from 0 - 48, higher score indicated worse disease state. |
| Percent Change From Baseline in IASI-S Scores at Week 16 | Baseline and Week 16 | IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-S= A1S x B1 X C1 + A2S x B2 x C2 + A3S x B3 x C3 + A4S x B4 x C4 IASI-S score ranged from 0 - 24, higher score indicated worse disease state. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From first dose up to study termination (maximum up to 9.4 weeks) | An AE was any untoward medical occurrence in a participant temporally associated with the use of a study treatment, whether or not considered related to the 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 adverse event, Inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, other important medical events. An adverse event was considered TE 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. |
| Percent Change From Baseline in IASI-E Scores at Week 16 | Baseline and Week 16 | IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-E= A1E x B1 x C1 + A2E x B2 x C2 + A3E x B3 x C3 + A4E x B4 x C4 IASI-E score ranged from 0 - 24, higher score indicated worse disease state. |
Countries
United States
Participant flow
Recruitment details
Participants with confirmed diagnosis of ichthyosis by genetic testing of ichthyosis were enrolled into the study.
Pre-assignment details
7 participants were screened for eligibility and 5 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. | 4 |
| Placebo Participants received imsidolimab matching placebo on Day 1 and thereafter, every 4 weeks (Days 29, 57 and 85) by subcutaneous injection. | 1 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Termination of the participant participation by the Investigator or Sponsor | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Imsidolimab |
|---|---|---|---|
| Age, Continuous | 66.0 years | 44.4 years STANDARD_DEVIATION 21.22 | 39.0 years STANDARD_DEVIATION 20.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 5 Participants | 4 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 | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 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 | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 1 |
| other Total, other adverse events | 1 / 4 | 1 / 1 |
| serious Total, serious adverse events | 0 / 4 | 0 / 1 |
Outcome results
Primary
Change From Baseline in Ichthyosis Area Severity Index (IASI) Total Score at Week 16
IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling & percentage of body surface area (BSA) affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 body regions (BR) \[A1: head & neck (H&N), A2: upper limbs (UL), A3: trunk (T), A4: lower limbs (LL)\]. Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value(0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6).Total extent was determined using multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-Erythema (E)= A1E x B1 x C1 + A2E x B2 x C2 + A3E x B3 x C3 + A4E x B4 x C4 (score 0 to 24) IASI-Scaling (S)= A1S x B1 X C1 + A2S x B2 x C2 + A3S x B3 x C3 + A4S x B4 x C4 (score 0 to 24) IASI total score= IASI-E + IASI-S score ranged from 0 - 48, higher score indicated worse disease state.
Time frame: Baseline and Week 16
Population: Due to early study termination before the primary time point, efficacy data was not collected, therefore, not analyzed.
Secondary
Change From Baseline in IASI-E Scores at Week 16
IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-E= A1E x B1 x C1 + A2E x B2 x C2 + A3E x B3 x C3 + A4E x B4 x C4 IASI-E score ranged from 0 - 24, higher score indicated worse disease state.
Time frame: Baseline and Week 16
Population: Due to early study termination before the primary time point, efficacy data was not collected, therefore, not analyzed.
Secondary
Change From Baseline in IASI-S Scores at Week 16
IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-S= A1S x B1 X C1 + A2S x B2 x C2 + A3S x B3 x C3 + A4S x B4 x C4 IASI-S score ranged from 0 - 24, higher score indicated worse disease state.
Time frame: Baseline and Week 16
Population: Due to early study termination before the primary time point, efficacy data was not collected, therefore, not analyzed.
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant temporally associated with the use of a study treatment, whether or not considered related to the 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 adverse event, Inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, other important medical events. An adverse event was considered TE 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 up to study termination (maximum up to 9.4 weeks)
Population: Safety analysis set included all randomized participants who received at least 1 dose of imsidolimab or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imsidolimab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 1 participants |
| Imsidolimab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAEs | 1 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 participants |
Secondary
Percentage of Participants Achieving an Improvement of 50% From Baseline in IASI (IASI50) at Week 16
IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-E= A1E x B1 x C1 + A2E x B2 x C2 + A3E x B3 x C3 + A4E x B4 x C4 (score 0 to 24) IASI-S= A1S x B1 X C1 + A2S x B2 x C2 + A3S x B3 x C3 + A4S x B4 x C4 (score 0 to 24) IASI total score= IASI-E + IASI-S score ranged from 0 - 48, higher score indicated worse disease state.
Time frame: Week 16
Population: Due to early study termination before the primary time point, efficacy data was not collected, therefore, not analyzed.
Secondary
Percent Change From Baseline in IASI-E Scores at Week 16
IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-E= A1E x B1 x C1 + A2E x B2 x C2 + A3E x B3 x C3 + A4E x B4 x C4 IASI-E score ranged from 0 - 24, higher score indicated worse disease state.
Time frame: Baseline and Week 16
Population: Due to early study termination before the primary time point, efficacy data was not collected, therefore, not analyzed.
Secondary
Percent Change From Baseline in IASI-S Scores at Week 16
IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-S= A1S x B1 X C1 + A2S x B2 x C2 + A3S x B3 x C3 + A4S x B4 x C4 IASI-S score ranged from 0 - 24, higher score indicated worse disease state.
Time frame: Baseline and Week 16
Population: Due to early study termination before the primary time point, efficacy data was not collected, therefore, not analyzed.
Secondary
Percent Change From Baseline in IASI Total Score at Week 16
IASI quantified the severity of participants ichthyosis based on severity of erythema/scaling, & percentage of BSA affected. Degree of erythema & scaling scored from 0 (none) to 4 (very severe) for each of 4 BR (A1: H&N, A2: UL, A3: T, A4: LL). Percentage of BSA involved for each BR (B1: % in H&N, B2: % in UL, B3: % in T, B4: % in LL). Percentage involvement was assigned numerical value (0= 0, 1%-9%= 1, 10%-29%= 2, 30%-49%= 3, 50%-69%= 4, 70%-89%= 5, 90%-100%= 6). Total extent was determined using a multiplier considering % of total BSA by each BR (C1= 0.1 for H&N; C2= 0.2 for UL; C3= 0.3 for T; C4= 0.4 for LL). IASI-E= A1E x B1 x C1 + A2E x B2 x C2 + A3E x B3 x C3 + A4E x B4 x C4 (score 0 to 24) IASI-S= A1S x B1 X C1 + A2S x B2 x C2 + A3S x B3 x C3 + A4S x B4 x C4 (score 0 to 24) IASI total score= IASI-E + IASI-S score ranged from 0 - 48, higher score indicated worse disease state.
Time frame: Baseline and Week 16
Population: Due to early study termination before the primary time point, efficacy data was not collected, therefore, not analyzed.