TABLE 4.
Summary of endpoints and additional analyses, intent‐to‐treat population from the APeX‐2 trial for berotralstat.
| Endpoint | Berotralstat 110 mg n = 41 | Berotralstat 150 mg n = 40 | Placebo n = 40 |
|---|---|---|---|
| Primary | |||
| Estimated monthly investigator‐confirmed attack rate through week 24 a | 1.65 | 1.31 | 2.35 |
| Attack rate ratio relative to placebo (95% CI) | 0.70 (0.51–0.95) | 0.56 (0.41–0.77) | – |
| p value | 0.24 | <0.001 | – |
| Secondary | |||
| Change from baseline to week 24 in AE‐QoL total score, least square means (standard error) b | −12.46 (2.53) | −14.59 (2.59) | −9.69 (2.64) |
| Difference from placebo, least square means (95% CI) | −2.77 (−10.08 to 4.53) | −4.90 (−12.23 to 2.43) | – |
| p value | 0.453 | 0.188 | – |
| Proportion of days with angioedema symptoms, least square means (standard error) c | 0.134 (0.019) | 0.119 (0.019) | 0.197 (0.020) |
| Difference from placebo, least square means (95% CI) | −0.062 (−0.117 to −0.008) | −0.078 (0.133 to −0.023) | – |
| Nominal p value | 0.025 | 0.006 | – |
| Estimated monthly confirmed attack rate over the effective dosing period (day 8 to week 24) a , d | 1.65 | 1.27 | 2.38 |
| Attack rate ratio relative to placebo (95% CI) | 0.70 (0.51–0.96) | 0.54 (0.39–0.74) | – |
| Nominal p value | 0.26 | <0.001 | – |
Abbreviations: AE‐QoL, angioedema‐quality of life; CI, confidence interval.
Investigator‐confirmed attack rate is defined as the total number of investigator‐confirmed HAE attacks experienced in the entire Part 1 dosing period. Statistical analysis is based on a negative binomial regression model in which the number of investigator‐confirmed attacks is included as the dependent variable, the treatment is included as a fixed effect, the baseline investigator‐confirmed attack rate is included as a covariate, and the logarithm of the duration of treatment is included as an offset variable.
The AE‐QoL scores range from 0 (best) to 100 (worst). Statistical analysis is based on a mixed‐model repeated measures analysis with baseline investigator‐confirmed attack rate, baseline AE‐QoL, treatment, visit, and visit‐by‐treatment interaction included as fixed effects. The patient is included as a random effect.
The proportion of days with angioedema symptoms due to investigator‐confirmed attacks is based on the number of days with reported symptoms from investigator‐confirmed attacks in Part 1 and the number of days the patient received treatment in Part 1. Statistical analysis is based on an analysis of the covariance model with baseline investigator‐confirmed attack rate as a covariate and treatment included as a fixed effect.
The effective dosing period is the steady‐state dosing period defined as days 8–168.
Source: Reprinted from J Allergy Clin Immunol, 148(1), Zuraw B, Lumry WR, Johnston DT, et al., Oral once‐daily berotralstat for the prevention of hereditary angioedema attacks: a randomized, double‐blind, placebo‐controlled phase 3 trial, 164–172, Copyright 2021, with permission from Elsevier. 37