Analysis of the Effect of Trofinetide Treatment on the Domain and Item-Level Responses of the Rett Syndrome Behavior Questionnaire Using Data From the LAVENDER Trial
Author(s)
Mirko V. Sikirica, PharmD1, Nazia Rashid, PharmD, MS2, Maria Lorenzi, MSc3, Benjamin G. Feakins, DPhil3, Sarah Cadarette, MPH3, Erika Wissinger, PhD3, Kitty Rajagopalan, BS, MS, PhD4, James M. Youakim, MD5;
1Acadia Pharmacueticals, Medical Affairs, San Diego, CA, USA, 2Acadia Pharmaceuticals, Medical Affairs, San Diego, CA, USA, 3Cencora, Evidence Generation & Value Communications, Conshohocken, PA, USA, 4Anlitiks Inc, HEOR, Windermere, FL, USA, 5Acadia Pharmaceuticals, Clinical Development, San Diego, CA, USA
1Acadia Pharmacueticals, Medical Affairs, San Diego, CA, USA, 2Acadia Pharmaceuticals, Medical Affairs, San Diego, CA, USA, 3Cencora, Evidence Generation & Value Communications, Conshohocken, PA, USA, 4Anlitiks Inc, HEOR, Windermere, FL, USA, 5Acadia Pharmaceuticals, Clinical Development, San Diego, CA, USA
Presentation Documents
OBJECTIVES: Examine the effect of trofinetide treatment on domain and item-level score changes on the caregiver-reported Rett Syndrome Behavior Questionnaire (RSBQ).
METHODS: Post-hoc analysis of the 12-week, double-blind, randomized, placebo-controlled, phase III study (LAVENDER; NCT04181723) of trofinetide was conducted to examine domain and item-level changes on the 45-item RSBQ. RSBQ assesses the impact of Rett Syndrome using a 3-point Likert scale (0 =behavior “not true”, 1 = behavior “somewhat/ sometimes true”, or 2 =behavior “often true”); with total score ranging from 0 to 90 (higher scores indicate increased severity). Percentage of patients with ≥1 point-level net reduction [net improvement, (NI)] or net increase [net worsening, (NW)] on the RSBQ domain and items from baseline to week 12 were compared between trofinetide and placebo. Results were also compared after accounting for thresholds for floor and ceiling effects, respectively, defined as: >50% patients’ responses at either lowest (score 0, i.e. cannot improve any-further) or highest (score 2, i.e. cannot worsen any-further) values.
RESULTS: At baseline, mean RSBQ-item response distribution among respondents was 30.0% (score 0), 39.4% (score 1) and 30.6% (score 2). Trofinetide demonstrated a NI of percentage of patients improving across all 8 domains and 41/45 items while placebo showed NI on 3 of 8 domains and 31/45 items. Overall, NI per item was numerically higher for trofinetide than the placebo NI per item in 37/45 items. Of the 8 RSBQ domains, three domains (12 items overall) had multiple items with ceiling effects and two domains (6 items overall) had floor effects. Trofinetide had similar NI results, after adjusting for ceiling and floor effects.
CONCLUSIONS: These analyses support trofinetide’s potential to improve Rett Syndrome across all 8 domains and 41 of the 45 items captured on the RSBQ. Similarly, NI were observed with trofinetide after accounting for floor and ceiling effects.
METHODS: Post-hoc analysis of the 12-week, double-blind, randomized, placebo-controlled, phase III study (LAVENDER; NCT04181723) of trofinetide was conducted to examine domain and item-level changes on the 45-item RSBQ. RSBQ assesses the impact of Rett Syndrome using a 3-point Likert scale (0 =behavior “not true”, 1 = behavior “somewhat/ sometimes true”, or 2 =behavior “often true”); with total score ranging from 0 to 90 (higher scores indicate increased severity). Percentage of patients with ≥1 point-level net reduction [net improvement, (NI)] or net increase [net worsening, (NW)] on the RSBQ domain and items from baseline to week 12 were compared between trofinetide and placebo. Results were also compared after accounting for thresholds for floor and ceiling effects, respectively, defined as: >50% patients’ responses at either lowest (score 0, i.e. cannot improve any-further) or highest (score 2, i.e. cannot worsen any-further) values.
RESULTS: At baseline, mean RSBQ-item response distribution among respondents was 30.0% (score 0), 39.4% (score 1) and 30.6% (score 2). Trofinetide demonstrated a NI of percentage of patients improving across all 8 domains and 41/45 items while placebo showed NI on 3 of 8 domains and 31/45 items. Overall, NI per item was numerically higher for trofinetide than the placebo NI per item in 37/45 items. Of the 8 RSBQ domains, three domains (12 items overall) had multiple items with ceiling effects and two domains (6 items overall) had floor effects. Trofinetide had similar NI results, after adjusting for ceiling and floor effects.
CONCLUSIONS: These analyses support trofinetide’s potential to improve Rett Syndrome across all 8 domains and 41 of the 45 items captured on the RSBQ. Similarly, NI were observed with trofinetide after accounting for floor and ceiling effects.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
PCR87
Topic
Patient-Centered Research
Topic Subcategory
Patient-reported Outcomes & Quality of Life Outcomes
Disease
SDC: Rare & Orphan Diseases