# Oral deucrictibant for on-demand treatment of hereditary angioedema attacks (RAPIDe-1): a randomised, double-blind, placebo-controlled, phase 2 trial

- **DOI:** [10.1016/s2352-3026(25)00341-2](https://doi.org/10.1016/s2352-3026(25)00341-2)
- **Rating:** Strong (4.2 out of 5)
- **Verdict:** A rigorous phase 2 crossover trial establishes short-term efficacy for oral deucrictibant, with selected attacks and a small safety dataset limiting clinical generalisation.
- **Framework version:** v5.9
- **Pipeline version:** v0.4
- **Evaluation date:** 2026-09-18
- **Evaluation page:** https://www.nabu.science/paper/10.1016%2Fs2352-3026(25)00341-2

## Key claims

1. In this phase 2 trial, we found that oral administration of deucrictibant 20 mg and 30 mg significantly reduced the severity of attack manifestations from pre-treatment to 4 h post-treatment.
   - Support: Well-supported
   - Type: Primary finding
   - Basis: blinded crossover estimates with multiplicity control and consistent prespecified sensitivity analyses
   - Location: Research in context, Added value of this study, p e201
2. Deucrictibant treatment also reduced the duration of attacks compared with placebo, with significant reductions in the time to onset of symptom relief and to resolution.
   - Support: Well-supported
   - Type: Secondary
   - Basis: multiplicity-controlled time-to-event endpoints consistently favoured the 20 mg and 30 mg doses
   - Location: Research in context, Added value of this study, p e201
3. The overall safety profile of deucrictibant was comparable to that of placebo
   - Support: Supported
   - Type: Secondary
   - Basis: systematic short-term adverse-event collection in a sample too small for uncommon or long-term harms
   - Location: Research in context, Added value of this study, p e201

## Strengths

- **Robust blinded crossover trial execution** Interactive-response randomisation, identical capsules, masking of participants, investigators, site personnel, and the sponsor, and within-patient crossover comparisons reduce allocation and measurement bias.
  - Dimension: methodological rigour
  - Location: Methods, Randomisation and masking, p e202
- **Consistent efficacy across endpoint families** The 20 mg and 30 mg doses improved VAS-3 severity, symptom-relief timing, MSCS, TOS, and rescue-medication use, with prespecified sensitivity analyses supporting the primary result.
  - Dimension: methodological rigour
  - Location: Table 2; Results, pp e207–09; appendix pp 9–10
- **Specific and integrated limitation analysis** The Discussion connects the excess of abdominal attacks and sparse 8–24-hour assessments to the unexpectedly short 10 mg resolution estimate, rather than listing these limitations generically.
  - Dimension: positioning
  - Location: Discussion, Limitations, pp e211–12

## Limitations

- **Small phase two efficacy population** Only 62 patients contributed to the primary efficacy analysis, with 16–21 patients represented in each active-dose cohort. This limits precision for dose selection and subgroup interpretation.
  - Dimension: methodological rigour
  - Location: Results, p e207; Table 2
- **Severe attack presentations were excluded** Attacks involving the internal head or neck, including laryngeal attacks, and attacks presenting with vomiting were not treated with study drug. The findings therefore do not establish efficacy for these consequential presentations.
  - Dimension: application pathway
  - Location: Methods, Procedures, p e202; Discussion, pp e211–12
- **Limited demographic and safety generalisation** The efficacy population was 97% White, and adverse events were assessed in a modest sample over short post-attack windows. Rare, long-term, and broadly representative safety cannot be established from this trial.
  - Dimension: application pathway
  - Location: Summary, p e200; Methods, p e203; Table 3

## Reliability checks

No concerns (4 of 4 checks).

- **Internal coherence:** Clean. Unanimous clean assessment: enrolment, analysis-set, attack-level, endpoint, multiplicity, and safety reporting are internally coherent across the paper. No methods–results mismatch, impossible statistic, or material overclaim was identified.
- **Research conduct:** Clean. Unanimous clean assessment: ethics approval, consent, prospective registration, sponsor participation, conflicts of interest, and the conditional data-sharing policy are disclosed. Sponsor involvement is extensive but transparent and does not itself establish a conduct concern.
- **Reference integrity:** Clean. 28 of 28 checkable references verified
  - 30 references in manuscript
  - 2 have no canonical index record — counted, but not index-checkable
  - 1 reference confirmed by manual review
  - References not verified automatically are resolved manually within 24 hours.

## Post-publication record

- **Status:** Clean
- **Summary:** No retraction or expression of concern found in Crossref (includes Retraction Watch).
- **Last checked:** 2026-10-17