OBJECTIVES: To identify key disease-related signs and symptoms (s/s) of CHAPLE disease, an ultra-rare, newly discovered genetic disease associated with severe complications causing premature death.

METHODS: Sixty-minute within-trial qualitative interviews were conducted with patients who have CHAPLE disease and/or their primary caregivers at the screening and week 24 visit of a trial of pozelimab treatment (NCT04209634). Patients ≥8 years old were the interview’s primary respondent; the primary respondent for patients <8 years old and those with cognitive impairment was the caregiver. If both the patient and their caregiver participated in the interview, the unit of analysis was the interview. Semi-structured interview guides were used by trained interviewers to explore the s/s of CHAPLE disease and, at screening, to identify the patient’s most bothersome s/s (MBS). Interviews were preferentially conducted in person. All were conducted in the dyad’s native language and were audio-recorded, transcribed, anonymized, and translated into English for coding and analysis.

RESULTS: Ten patients were enrolled in the trial (median age at screening: 8.5 years [range: 3–19], 60% female, 70% interviewed in Turkey); 50% of interviews were conducted as a dyad at screening and 60% were conducted as a dyad at week 24. Thirty-one CHAPLE-related s/s were reported during the interviews. The core s/s of CHAPLE were (% having experienced s/s): abdominal pain (100%), facial edema (100%), peripheral edema (100%), diarrhea (100%), vomiting (100%), and nausea (90%). The MBS reported were abdominal pain (n=9), and facial edema (n=1); with n=7/10 and n=2/10 patients identifying these s/s as most important to improve with treatment, respectively. Other s/s experienced by ≥3 patients included fever, bowel incontinence, and headaches.

CONCLUSIONS: Patients with CHAPLE disease experience a core set of six s/s with the most critical aspect being abdominal pain, suggesting a relatively homogeneous experience of disease.