Patients in SYNAPSE had recurrent nasal polyps with a need for surgery

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SYNAPSE study design

SYNAPSE baseline characteristics

All primary and secondary endpoints were met with statistical significance.1

SYNAPSE study1

RUN-IN PERIOD

Weeks –4 to 0
all patients received SOC

TREATMENT PERIOD
52 weeks: N=407

NUCALA + SOC
(n=206)

or

Placebo + SOC
(n=201)

FOLLOW-UP PERIOD

24 weeks

To Week 76 in a subset of patients
(n=134)


Description
52-week, multicenter, randomized, double-blind, placebo-controlled, Phase 3 study with NUCALA 100 mg or placebo SC once every 4 weeks added to SOC* in 407 adult patients with recurrent chronic rhinosinusitis with nasal polyps.

*Defined as daily mometasone furoate nasal spray in addition to saline nasal irrigations, and courses of systemic corticosteroids (SCS) and/or antibiotics as required.

Select inclusion criteria

  • At least 1 prior endoscopic nasal polyp surgery for the removal of nasal polyps over the past 10 years
  • Intranasal corticosteroid therapy for >8 weeks prescreening
  • Endoscopic bilateral nasal polyps score >5 out of a maximum of 8 (range of 0 to 4 in each nostril; higher score indicates worse status)
  • Nasal obstruction symptom score >5 out of a maximum of 10 (ranges from 0=none to 10=as bad as you can imagine)
  • Overall nasal polyp symptom score >7 out of a maximum of 10 (ranges from 0=none to 10=as bad as you can imagine)

Co-primary endpoints/results

  • LS mean change from baseline in total endoscopic nasal polyp score (centrally read) at Week 52: NUCALA + SOC, –0.87, vs placebo + SOC, 0.06; P<0.001.
  • LS mean change from baseline in nasal obstruction score during Weeks 49-52. NUCALA + SOC, –4.40 vs placebo + SOC, –2.54; P<0.001.

LS means from an analysis using mixed model repeated measures with covariates of treatment group, geographic region, baseline score, and log(e) baseline blood eosinophil count visit, interaction terms for visit by baseline and visit by treatment.

Key secondary endpoint

  • Time to first nasal polyp surgery up to Week 52
    • Defined as any procedure involving instruments resulting in incision and removal of tissue (polypectomy) in the nasal cavity and the sinuses

Select secondary endpoints

  • Change from baseline in overall symptom score at Weeks 49-52
  • Change from baseline in mean individual symptom score for loss of smell at Weeks 49-52
  • Change from baseline in SNOT-22 total score at Week 52
  • Proportion of patients requiring systemic steroids for nasal polyps up to Week 52

Symptom scores

  • Based on daily patient-reported symptom severity using visual analogue scale (VAS) of 0 to 10 (0=none, 10=as bad as you can imagine)
  • Symptoms reported included nasal obstruction, nasal discharge, mucus in throat, facial pain, loss of smell

SNOT-223

  • A disease-specific measure of health-related quality of life that includes 22 items assessing symptoms and symptom impact associated with CRS
  • Score ranges from 0 to 110, with each item scored from 0 (no problem) to 5 (the problem is as bad as it can be)
  • 6 domains: nasal, non-nasal, ear/facial, sleep, fatigue, and emotional consequences 

Nasal polyp score (NPS)

  • Polyps on each side of the nose were graded on a categorical scale (0=no polyps, 1=small polyps in the middle meatus not reaching below the inferior border of the middle concha, 2=polyps reaching below the lower border of the middle turbinate, 3=large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha, 4=large polyps causing almost complete congestion/obstruction of the inferior meatus)
  • Total score (sum of both nostrils) ranged from 0 to 8

SYNAPSE baseline characteristics

All patients in SYNAPSE had severe recurrent nasal polyps with a need for repeat surgery.

Summary of baseline characteristics (n=407)1,2
  NUCALA (n=206) Placebo (n=201)
Age in years, mean (SD) 48.6 (13.6) 48.9 (12.5)
Female, n (%) 67 (33)
 76 (38)
Blood eosinophil level (cells/μL), geometric mean 390 400
Duration of nasal polyps in years, mean (SD) 11.4 (8.5) 11.5 (8.3)
Previous surgeries† for NP in past 10 years, n (%)    

0

1

2

≥3

0

108 (52)

47 (23)

51 (25)

0

81 (40)

47 (23)

73 (36)
Number of SCS courses for NP in previous 12 months, n (%)    

0

1

2

>2

100 (49)

64 (31)

17 (8)

25 (12)

110 (55)

47 (23)

18 (9)

26 (13)
Total endoscopic NP score (centrally read), mean (SD)‡ 5.4 (1.2) 5.6 (1.4)
Nasal obstruction symptom VAS score, mean (SD)‡ 8.9 (0.8) 9.0 (0.8)
Overall symptom VAS score, mean (SD)‡ 9.0 (0.8) 9.1 (0.7)
Loss of smell symptom VAS score, mean (SD)‡ 9.6 (0.8) 9.7 (0.6)
SNOT-22 total score, mean (SD)‡ 63.7 (17.6)
 64.4 (19.0)

Participants with asthma n, (%)

ACQ-5 score, mean (SD)§

140 (68)

2.38 (1.36)

149 (74)

2.15 (1.36)
Participants with AERD n, (%) 45 (22) 63 (31)

 

†Defined as any procedure involving instruments resulting in incision and removal of tissue (polypectomy) in the nasal cavity and the sinuses.

‡Higher scores indicate greater disease severity.

§ACQ-5 score of ≥1.5 indicates poorly controlled asthma.4

ACQ=Asthma Control Questionnaire; AERD=aspirin-exacerbated respiratory disease; CRS=chronic rhinosinusitis; LS=least squares; NP=nasal polyps; SC=subcutaneous; SD=standard deviation; SNOT-22=sino-nasal outcome test (22-item); SOC=standard of care.

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