Prevalence of KIT D816V in systemic MCA

• Research type

  Research Study

• Full title

  Study evaluating the prevalence of the KIT D816V mutation in peripheral blood of patients with evidence of systemic mast cell activation (MCA)

• IRAS ID

  300851

• Contact name

  Bethan Myers

• Contact email

  bethan.myers@uhl-tr.nhs.uk

• Sponsor organisation

  Blueprint Medicines

• ISRCTN Number

  ISRCTN00000000

• Clinicaltrials.gov Identifier

  NCT04811365

• Clinicaltrials.gov Identifier

  N/A, N/A

• Duration of Study in the UK

  0 years, 8 months, 30 days

• Research summary

  Research Summary
  Blueprint Medicines is conducting a research study to test for a change in a gene called KIT that can be found in the blood to understand its relationship with the symptoms indicative of a condition related to mast cell activation. This condition is often related to severe allergic reactions. Mast cells are a kind of cells in the human body that are found in blood and other organs, and they play an important role in allergic reactions. This information will help doctors better understand the association of this mutation with mast cell activation and may lead to improved methods for diagnosis.

  The study will be conducted at multiple study centres in the United States, the United Kingdom, Canada, and Europe with about 400 patients.

  Participation will be approximately 3 days, involving a screening period, one study visit and a follow-up period. The study visit will last about 1-2 hours. Participation may be longer in case side effects from the study-related procedures are experienced.

  Participants will undergo the following procedures: Medical history, blood sample, cheek swab and a follow up phone call.

  Summary of results
  In total, 385 patients from 22 sites were screened and 381 patients were considered eligible for enrolment. Of the
  381 enrolled patients, 379 (>99%) patients completed the study while two patients discontinued the study as they were unable to provide a blood sample. The KIT D816V analysis population included 371 patients as for eight patients with a blood sample drawn, their blood sample either was either not received (n=2) or was received by the central laboratory past stability (n=6) and no re-draw could be done.
  The mean age of the 381 patients was 53.7 years (SD 14.85), and most patients were female (59.6%). Most patients were White (77.4%) and not of Hispanic or Latino ethnicity (63.0%). While patients could meet eligibility by meeting one or more of the inclusion criteria under inclusion criterion 3, most patients only met one of the criteria as evidence of systemic MCA. The most common prior and concomitant medications for the Enrolled Population were antihistamines (30%), drugs for peptic ulcer and gastro-esophageal reflux disease (24%), and lipid modifying agents (20%). Episodic tryptase elevations were present in 98 of the 381 enrolled patients, of whom 63
  (64.3%) met the diagnostic threshold for MCA.
  Primary Endpoint Results:
  • Fifteen of the 371 patients in the KIT D816V analysis population had a KIT D816V mutation detected resulting in a prevalence of 4.0% of the KIT D816V mutation in PB.
  • It should be noted that there were at least 5 patients within the first 99 PB samples tested who were initially regarded positive for the KIT D816V mutation (KIT D816V MAF <0.03, but greater than 0) who were later re-assessed and considered “not-detected”. When extrapolating this finding across the full systemic MCA population (n=381), potentially 18-20 additional KIT D816V positive patients may have been detected, which would increase our reported KIT D816V mutation prevalence of 4% to about 10%.
  Secondary Endpoints Results:
  • The mean KIT D816V MAF in PB among patients positive for KIT D816V was 4.1% (SD 10.84; median 0.1; min, 0.0 and max 37.4).
  • Of the 381 patients in the Enrolled Population:
  o 138 patients (36.2%) were considered to have HaT.
  o 38.3% had sBT levels between 0-8 ng/mL and 42.3% had levels between 8-20 ng/mL, but only one patient (6.7%) with the KIT D816V mutation and none with HaT fell within the 0-8 ng/mL range.
  o The mean REMA score was similar among patients with and without the KIT D816V mutation but differed between patients with and without HaT.
  Safety Results:
  • Most patients (n=373; 97.9%) did not experience AEs related to the blood and buccal swab sampling procedures. Seven patients (1.8%) reported a mild

• REC name

  London - Bromley Research Ethics Committee

• REC reference

  21/PR/1176

• Date of REC Opinion

  24 Nov 2021

• REC opinion

  Further Information Favourable Opinion