Targeted therapies to improve CFTR function in cystic fibrosis

Table 3 Summary of clinical studies investigating the efficacy of ivacaftor in patients with cystic fibrosis mutations other than Gly551Asp

Study name and reference	Flume et al. 2012 [54]	KONNECTION: De Boeck et al. 2014 [51]	KONDUCT: Moss et al. 2015 [53]
Type of study	Phase II RCT with open label extension	Phase III randomized crossover trial with open label extension	Phase III RCT
Number of participants	n = 104	n = 39	n = 69
Number of participants	n = 104	n = 39	Ivacaftor 34; placebo 35
Duration	16 weeks (96-week extension)	24 weeks (total)	24 weeks
		8 weeks placebo/ivacaftor
		8 weeks ivacaftor/placebo
		12 weeks ivacaftor
Inclusion criteria	≥12 years	≥6 years	≥6 years
	Phe508del homozygous	>1 non-Gly551Asp gating mutation	>1 Arg117His mutation
	FEV₁ > 40 %	FEV₁ > 40 %	FEV₁ > 40–90 % (>12 years)
			FEV₁ > 40–105 % (6–11 years)
			Weight >15 kg
Outcome measure	Treatment effect	Treatment effect after 8 weeks	Treatment effect
Mean FEV₁ (percentage predicted)	+1.7 (P = 0.15)	+10.7 (P < 0.0001)	All ages: +2.1 (P = 0.2)
			>18 years: +5 (P = 0.01)
			6–11 years: −6.3 (P = 0.03)
Sweat chloride levels (mmol/L)	−2.9 (P = 0.04)	−49.2 (P < 0.0001)	−24 (P < 0.0001)
CFQ-R score (points)	No significant differences	+9.6 (P = 0.0004)	+8.4 (P = 0.009)
Weight (kg)	No significant differences	–	–
BMI	No significant differences	BMI-for-age z-score 0.28 (P = 0.001)	–

BMI body mass index (the weight in kilograms divided by the square of the height in meters), CFQ-R revised Cystic Fibrosis Questionnaire, FEV ₁ percentage predicted forced expiratory volume in 1 second for age, sex and height, RCT randomized controlled trial

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