Drug Trials Snapshot: EUCRISA
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to EUCRISA Prescribing Information for complete information.
EUCRISA (crisaborole)
(you-KRIS-a)
Anacor Pharmaceuticals
Approval date: December 14, 2016
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
EUCRISA is a drug for treatment of mild to moderate atopic dermatitis in patients 2 years of age and older.
Atopic dermatitis is an inflammatory skin disease that occurs primarily in children and younger adults.
How is this drug used?
EUCRISA is an ointment. It is applied two times a day in a thin layer to the areas of skin where atopic dermatitis is present.
What are the benefits of this drug?
More patients achieved clear or almost clear skin after treatment with EUCRISA in comparison to those who were treated with placebo ointment.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results for the clinical trials based on the primary efficacy endpoint defined as the proportion of participants at Day 29 who achieved success. Success was defined as an ISGA grade of Clear (score of 0) or Almost Clear (score of 1) with a 2-grade or greater improvement from baseline, comparing EUCRISA-treated participants to vehicle-treated participants.
Table 2. Primary Efficacy Outcomes in Participants with Mild to Moderate Atopic Dermatitis at Day 29
| Trial 1 | Trial 2 | |||
|---|---|---|---|---|
| EUCRISA (N=503) |
Vehicle (N=256) |
EUCRISA (N=513) |
Vehicle (N=250) |
|
| Success in ISGAa | 32.8% | 25.4% | 31.4% | 18.0% |
aDefined as an ISGA score of Clear (0) or Almost Clear (1) with a 2-grade or greater improvement from baseline.
EUCRISA Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: EUCRISA worked better in female than in male participants.
- Race: EUCRISA worked better in White than in Black or African American participants. The number of participants in other races was limited; therefore, differences in response among all races could not be determined.
- Age: EUCRISA worked similarly in all age groups studied. The number of participants above 65 years of age was limited; therefore, differences in response between participants above and below 65 years of age could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Figures below summarize efficacy results by subgroup for each trial based on the ITT population.
Figure 4. Results for the Primary Efficacy Endpoint at Day 29 by Gender, Age and Race, for Trial 1 (ITT, MI)*
n[E] = subgroup sample size in EUCRISA arm, n[V] = subgroup sample size in vehicle arm
95% CI for forest plot
ISGA= Investigator’s Static Global Assessment
*ITT=Intent -to-Treat; MI=multiple imputations
FDA Statistical review
Figure 5. Results for the Primary Efficacy Endpoints at Day 29 by Gender, Age and Race, for Trial 2 (ITT, MI)*
n[E] = subgroup sample size in EUCRISA arm, n[V] = subgroup sample size in vehicle arm
95% CI for forest plot
ISGA= Investigator’s Static Global Assessment
*ITT=Intent -to-Treat; MI=multiple imputations
FDA Statistical review
What are the possible side effects?
The most common side effect of EUCRISA is pain at the application site.
EUCRISA may cause allergic reactions at or near the application site. These can be serious and may include hives, itching, swelling, and redness.
What are the possible side effects?
The table below summarizes adverse reactions that occurred in clinical trials. Presented is the safety population that includes all participants who applied the treatment at least once.
Table 3. Adverse Reaction Occurring in ≥1% of Participants in Atopic Dermatitis Trials through Week 4 (safety population)
| Adverse Reaction | EUCRISA N=1012 n (%) |
Vehicle N=499 n (%) |
|---|---|---|
| Application site paina | 45 (4) | 6 (1) |
aRefers to skin sensations such as burning or stinging.
EUCRISA Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The risk of side effects was similar in male and female participants.
- Race: The risk of side effects was higher in White than in Black or African American participants. The number of participants in other races was limited; therefore, differences in side effects among all races could not be determined.
- Age: The risk of side effects was similar in all age groups studied. The number of participants above 65 years of age was limited; therefore, differences in side effects between participants above and below 65 years of age could not be determined.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes subgroups of participants who reported an adverse reaction of application site pain during clinical trials.
Table 4. Subgroup Analysis of Adverse Reaction -Application Site Pain (safety population)
| Subgroup | EUCRISA (N=1012) m/n* (%) |
Vehicle (N=499) m/n* (%) |
|---|---|---|
| Sex | ||
| Male | 19/448 (4.2) | 3/220 (1.4) |
| Female | 26/564 (4.6) | 3/279 (1.1) |
| Age Group (years) | ||
| 2-6 | 12/333 (3.6) | 2/168 (1.2) |
| 7-11 | 16/292 (5.5) | 1/143 (0.7) |
| 12-17 | 10/246 (4.1) | 1/122(0.8) |
| ≥18 | 7/141 (5) | 2/66 (3) |
| Race | ||
| White | 30/615 (4.9) | 4/303 (1.3) |
| Black or African American | 8/283 (2.8) | 0/136 (0) |
| Asian | 1/52 (1.9) | 1/27 (3.7) |
| American Indian or Alaska Native | 2/11( 18.3) | 0/5 (0) |
| Native Hawaiian or Other Pacific Islander | 1/7 (14.3) | 0/8 (0) |
| Other | 3/44 (6.8) | 1/20 (5) |
*m/n= number of participants with adverse reaction (m) in the subgroup (n)
Clinical trial data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved EUCLISA based on evidence from two clinical trials of 1522 participants with mild to moderate atopic dermatitis. The trials were conducted in the USA.
The figure below summarizes how many males and females were in the clinical trials.
Figure 1. Baseline Demographics by Sex
FDA Statistical review
Figure 2 and Table 1 below summarize the percentage of participants by race in the clinical trials.
Figure 2. Baseline Demographics by Race
FDA Statistical review
Table 1. Baseline Demographics by Race
| Race | Number of Participants | Percentage |
|---|---|---|
| White | 923 | 61 |
| Black or African American | 424 | 28 |
| Asian | 79 | 5 |
| American Indian or Alaska Native | 16 | 1 |
| Native Hawaiian or Other Pacific Islander | 15 | 1 |
| Other | 65 | 4 |
FDA Statistical review
Figure 3 summarizes the percentage of participants by age enrolled in the clinical trials.
Figure 3. Baseline Demographics by Age
FDA Statistical review
Who participated in the trials?
The table below summarizes participants by subgroup for the ITT population in the clinical trials.
Table 5. Baseline Demographics of Participants in the Clinical Trials (ITT population)
|
Trial 1 |
Trial 2 |
|||
|---|---|---|---|---|
| EUCRISA (N=503) |
Vehicle (N=256) |
EUCRISA (N=513) |
Vehicle (N=250) |
|
| Age (years) | ||||
| Mean (SD) | 12.0 (11.6) | 12.4 (10.7) | 12.6 (12.7) | 11.8 (12.6) |
| Median | 9.0 | 10.0 | 9.0 | 8.5 |
| Range | 2 – 65 | 2 – 63 | 2 – 79 | 2 – 79 |
| Age Groups (years) | ||||
| 2-6 | 162 (32%) | 78 (30%) | 173 (34%) | 93 (37%) |
| 7-11 | 155 (31%) | 73 (29%) | 137 (27%) | 71 (28%) |
| 12-17 | 121 (24%) | 67 (26%) | 126 (25%) | 57 (23%) |
| 18+ | 65 (13%) | 38 (15%) | 77 (15%) | 29 (12%) |
| Gender | ||||
| Male | 219 (44%) | 113 (44%) | 231 (45%) | 112 (45%) |
| Female | 284 (56%) | 143 (56%) | 282 (55%) | 138 (55%) |
| Race | ||||
| White | 308 (61%) | 162 (63%) | 309 (60%) | 144 (58%) |
| Black | 138 (27%) | 61 (24%) | 147 (29%) | 78 (31%) |
| Asian | 26 (5%) | 17 (7%) | 26 (5%) | 10 (4%) |
| American Indian or Alaska Native | 8 (2%) | 3 (1%) | 3 (1%) | 2 (1%) |
| Native Hawaiian or Other Pacific Islander |
0 | 4 (2%) | 7 (1%) | 4 (2%) |
| Other | 23 (5%) | 9 (4%) | 21 (4%) | 12 (5%) |
Adapted from FDA Statistical review
How were the trials designed?
The benefit and side effects of EUCRISA were evaluated in two clinical trials of participants with mild to moderate atopic dermatitis. In both trials participants received treatment with either EUCRISA or placebo twice daily for 28 days. Neither the participants nor the health care providers knew which treatment was being given until after the trials were completed.
Participants were evaluated for improvement of atopic dermatitis from the first to the last day of treatment. The improvement was measured at Day 29 using the Investigator’s Static Global Assessment [ISGA] score that measures the severity of disease on a scale from 0 to 5.
How were the trials designed?
The safety and efficacy of EUCRISA were established in 2 randomized, double-blind, vehicle-controlled trials of 4 weeks duration. All participants had mild to moderate atopic dermatitis defined as score of 2 or 3 using an Investigator’s Static Global Assessment [ISGA]. In both trials, participants were randomized 2:1 to receive EUCRISA or vehicle applied twice daily for 28 days.
The primary efficacy outcome measure was the proportion of participants at Day 29 who achieved success, defined as an ISGA grade of Clear (score of 0) or Almost Clear (score of 1) with a 2-grade or greater improvement from baseline, comparing EUCRISA-treated participants to vehicle-treated participants.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.