14 CLINICAL STUDIES
The efficacy of CIBINQO as monotherapy and in combination with background topical corticosteroids were evaluated in 3 randomized, double-blind, placebo-controlled trials [Trial-AD-1 (NCT03349060), Trial-AD-2 (NCT03575871), and Trial-AD-3 (NCT03720470)] in 1615 subjects 12 years of age and older (CIBINQO is not approved for use in pediatric patients) with moderate-to-severe atopic dermatitis as defined by Investigator's Global Assessment (IGA) score ≥3, Eczema Area and Severity Index (EASI) score ≥16, body surface area (BSA) involvement ≥10%, and Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 at the baseline visit prior to randomization.
Overall, 53% of subjects were male, 69% of subjects were white, 64% of subjects had a baseline IGA score of 3 (moderate AD), and 36% of subjects had a baseline IGA score of 4 (severe AD). The baseline mean EASI score was 30. The baseline mean age was 36 years old with 8% of subjects 12 to less than 18 years old and 92% of subjects 18 years of age or older. Subjects in these trials were those who had inadequate response to previous topical therapy, or were subjects for whom topical treatments were medically inadvisable, or who had received systemic therapies including dupilumab. In each of the trials, over 40% of subjects had prior exposure to systemic therapy. In Trial-AD-1 and Trial-AD-2, 6% of the subjects had received dupilumab, whereas prior use of dupilumab was not allowed in Trial-AD-3.
Trial-AD-1, Trial-AD-2, and Trial-AD-3 assessed the co-primary endpoints of IGA and EASI-75 responses at Week 12. The designs of the trials are summarized in Table 8.
| Study Name (regimen type) Treatment Duration | Population (number of randomized and dosed subjects) | Treatment Arms | Co-Primary Endpoints |
|---|---|---|---|
| Abbreviations: EASI=Eczema Area and Severity Index; IGA=Investigator's Global Assessment; QD=once daily; Q2W=once every 2 weeks. | |||
| |||
| Trial-AD-1 (monotherapy) 12 weeks | *Subjects 12 years of age or older (387) | Oral administration of:
| |
| Trial-AD-2 (monotherapy) 12 weeks | *Subjects 12 years of age or older (391) | Oral administration of:
| |
| Trial-AD-3 (combination therapy) 16 weeks | Subjects 18 years of age or older (837) | Oral administration of:
| |
Clinical Response
Monotherapy Trials
The results of the CIBINQO monotherapy trials (Trial-AD-1 and Trial-AD-2) are presented in Table 9.
| Trial-AD-1 | Trial-AD-2 | |||||
|---|---|---|---|---|---|---|
| CIBINQO | Placebo N=77 | CIBINQO | Placebo N=78 | |||
| 200 mg QD N=154 | 100 mg QD N=156 | 200 mg QD N=155 | 100 mg QD N=158 | |||
| Abbreviations: CI=confidence interval; EASI=Eczema Area and Severity Index; IGA=Investigator Global Assessment; QD=once daily. | ||||||
| IGA 0 or 1* | 44% | 24% | 8% | 38% | 28% | 9% |
| Difference from Placebo (95% CI) | 36% (26%, 46%) | 16% (7%, 25%) | - | 29% (19%, 39%) | 19% (9%, 29%) | - |
| EASI-75† | 62% | 40% | 12% | 61% | 44% | 10% |
| Difference from Placebo (95% CI) | 51% (40%, 61%) | 28% (18%, 39%) | - | 50% (40%, 61%) | 33% (23%, 44%) | - |
The proportion of subjects achieving PP-NRS4 at Week 2 (defined as an improvement of ≥4 points from baseline in PP-NRS) was higher in subjects treated with CIBINQO monotherapy 200 mg once daily (28% in Trial-AD-1 and 24% in Trial-AD-2) and 100 mg once daily (11% in both trials) compared to placebo (2% in both trials).
A higher proportion of subjects in the CIBINQO monotherapy 100 mg or 200 mg once daily arm compared to placebo achieved improvement in itching at Week 12.
Combination Therapy Trial
The results of CIBINQO in combination with background topical corticosteroids (Trial-AD-3) are presented in Table 10.
| % Responders | CIBINQO | Placebo N=131 | |
|---|---|---|---|
| 200 mg QD N=226 | 100 mg QD N=238 | ||
| Abbreviations: CI=confidence interval; EASI=Eczema Area and Severity Index; IGA=Investigator Global Assessment; QD=once daily. | |||
| IGA 0 or 1*at Week 12 | 47% | 36% | 14% |
| Difference from Placebo (95% CI) | 34% (25%, 42%) | 23% (15%, 31%) | - |
| EASI-75† at Week 12 | 68% | 58% | 27% |
| Difference from Placebo (95% CI) | 41% (32%, 51%) | 32% (22%, 41%) | - |
The proportions of subjects achieving PP-NRS4 at Week 2 was higher in subjects treated with CIBINQO 200 mg once daily (30%) and 100 mg once daily (14%) in combination with background medicated topical therapies compared to placebo (8%).
Examination of age, gender, race, weight and previous systemic AD therapy treatment did not identify differences in response to CIBINQO 100 mg or 200 mg once daily among these subgroups in Trial-AD-1, Trial-AD-2, and Trial-AD-3.