(257) Within-Trial Interviews to Contextualize the Patient Experience and Supplement Clinical Outcomes Assessments in a Pivotal Trial of a Newly Described, Fatal and Ultra-Rare Pediatric Disease

Background: CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) disease affects < 100 patients worldwide, primarily children, and can be fatal.

Objectives: A mixed-methods approach combining data from within-trial interviews and clinical outcome assessments (COAs) was used to assess treatment effect of pozelimab on CHAPLE disease signs/symptoms from the patient perspective in the pivotal trial (ClinicalTrials.gov, NCT04209634).

Methods: Interviews conducted with all patients/caregivers at screening and week 24 assessed CHAPLE disease signs/symptoms, identified the most bothersome signs/symptoms, and evaluated change in signs/symptoms. The primary respondent was the patient if aged ≥8 years and the caregiver for patients < 8 years, although patients were encouraged to participate in interviews. Patients/caregivers and clinicians completed COAs and global assessments of symptom/severity and change during the trial; interview data contextualized meaningfulness of change.

Results: Ten patients (aged 3–19 years) were enrolled; caregivers contributed to 9/10 interviews. Abdominal pain, diarrhea, facial and peripheral edema, nausea, and vomiting were core signs/symptoms of CHAPLE disease (≥90% patients experienced pre-treatment); for 9 patients, the most bothersome signs/symptoms was abdominal pain. Improvement in 18/19 signs/symptoms was reported during week 24 interviews, including a complete resolution of core signs/symptoms. No patient experienced worsening in signs/symptoms, although ability to gain weight was unchanged for one patient. Severity on patient/caregiver and clinician globals ranging from “mild” to “very severe” at baseline improved to “no signs or symptoms” at week 24. Interview results were generally consistent with signs/symptoms-specific COA scores.

Conclusions: Patients with CHAPLE disease treated with pozelimab for 24 weeks experienced improvement in the majority of signs/symptoms and complete resolution of all core signs/symptoms. Mixed-methods approaches contextualized the patient experience by providing complementary and supplementary information on the patient experience beyond the COAs. Such approaches may be supportive in demonstrating drug efficacy, especially in the context of rare and severe diseases.