Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of TEZ/IVA in Subjects Aged 6 Through 11 Years With Cystic Fibrosis (NCT NCT03559062)

Last Updated: 2020-02-11

Results Overview

LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

67 participants

Primary outcome timeframe

From baseline through Week 8

Results posted on

2020-02-11

Participant Flow

A total of 69 participants were randomized, out of which 67 participants received study drug and were included in participant flow and baseline characteristics section.

Participant milestones

Participant milestones
Measure	Placebo Participants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks.	TEZ/IVA Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	Ivacaftor Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks.
Overall Study STARTED	10	54	3
Overall Study COMPLETED	10	53	3
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks.	TEZ/IVA Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	Ivacaftor Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks.
Overall Study Other	0	1	0

Baseline Characteristics

A Study to Evaluate Efficacy and Safety of TEZ/IVA in Subjects Aged 6 Through 11 Years With Cystic Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=10 Participants Participants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks.	TEZ/IVA n=54 Participants Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	Ivacaftor n=3 Participants Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks.	Total n=67 Participants Total of all reporting groups
Age, Continuous	9.0 years STANDARD_DEVIATION 1.7 • n=5 Participants	8.5 years STANDARD_DEVIATION 1.7 • n=7 Participants	9.0 years STANDARD_DEVIATION 1.7 • n=5 Participants	8.6 years STANDARD_DEVIATION 1.7 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	29 Participants n=7 Participants	2 Participants n=5 Participants	37 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	25 Participants n=7 Participants	1 Participants n=5 Participants	30 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	46 Participants n=7 Participants	3 Participants n=5 Participants	59 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	7 Participants n=7 Participants	0 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	51 Participants n=7 Participants	3 Participants n=5 Participants	64 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Lung Clearance Index 2.5 (LCI2.5)	9.67 lung clearance index STANDARD_DEVIATION 1.65 • n=5 Participants	9.56 lung clearance index STANDARD_DEVIATION 2.06 • n=7 Participants	8.60 lung clearance index STANDARD_DEVIATION 1.40 • n=5 Participants	9.54 lung clearance index STANDARD_DEVIATION 1.97 • n=4 Participants

PRIMARY outcome

Timeframe: From baseline through Week 8

Population: Full Analysis Set: all participants who were randomized, received at least 1 dose of study drug and had an eligible genotype. As per the pre-specified analysis, efficacy was only planned to be assessed for TEZ/IVA group. Placebo or IVA groups were used for blinding purposes only and were not applicable for the purpose of primary efficacy analysis.

LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

Outcome measures

Outcome measures
Measure	TEZ/IVA n=54 Participants Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	TEZ/IVA Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	Ivacaftor Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks.
Absolute Change in Lung Clearance Index 2.5 (LCI2.5) Through Week 8	-0.51 lung clearance index Standard Error 0.11	—	—

SECONDARY outcome

Timeframe: From baseline at Week 8

Population: FAS. As per the pre-specified analysis, efficacy was only planned to be assessed for TEZ/IVA group. Placebo or IVA groups were used for blinding purposes only and were not applicable for the purpose of secondary efficacy analysis.

Sweat samples were collected using an approved collection device.

Outcome measures

Outcome measures
Measure	TEZ/IVA n=54 Participants Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	TEZ/IVA Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	Ivacaftor Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks.
Absolute Change in Sweat Chloride At Week 8	-12.3 millimole per liter (mmol/L) Standard Error 1.5	—	—

SECONDARY outcome

Timeframe: From baseline through Week 8

The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

Outcome measures

Outcome measures
Measure	TEZ/IVA n=54 Participants Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	TEZ/IVA Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	Ivacaftor Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8	2.3 units on a scale Standard Error 1.2	—	—

SECONDARY outcome

Timeframe: From first dose of study drug up to safety follow-up visit (up to Week 12)

Population: Safety set included all participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	TEZ/IVA n=10 Participants Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	TEZ/IVA n=54 Participants Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	Ivacaftor n=3 Participants Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks.
Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Safety Follow-up Visit Participants with SAEs	0 Participants	0 Participants	0 Participants
Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Safety Follow-up Visit Participants with AEs	8 Participants	41 Participants	2 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

TEZ/IVA

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Ivacaftor

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: 617-341-6777

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=10 participants at risk Participants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks.	TEZ/IVA n=54 participants at risk Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.	Ivacaftor n=3 participants at risk Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks.
Injury, poisoning and procedural complications Thermal burn	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	33.3% 1/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Investigations Alanine aminotransferase increased	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Investigations Aspartate aminotransferase increased	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	16.7% 9/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Respiratory, thoracic and mediastinal disorders Sputum increased	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	5.6% 3/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	33.3% 1/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Respiratory, thoracic and mediastinal disorders Productive cough	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	13.0% 7/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	5.6% 3/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Respiratory, thoracic and mediastinal disorders Throat irritation	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Nervous system disorders Headache	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	14.8% 8/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Gastrointestinal disorders Vomiting	0.00% 0/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	7.4% 4/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Gastrointestinal disorders Abdominal pain	0.00% 0/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	5.6% 3/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Skin and subcutaneous tissue disorders Rash	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Skin and subcutaneous tissue disorders Blister	0.00% 0/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	33.3% 1/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Musculoskeletal and connective tissue disorders Arthritis	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	20.0% 2/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	5.6% 3/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Infections and infestations Gastroenteritis	0.00% 0/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	7.4% 4/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Infections and infestations Bacterial disease carrier	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Infections and infestations Nasopharyngitis	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	9.3% 5/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Infections and infestations Otitis media	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Infections and infestations Rhinitis	10.0% 1/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Infections and infestations Impetigo	0.00% 0/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	33.3% 1/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Infections and infestations Upper respiratory tract infection	0.00% 0/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	33.3% 1/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/10 • From first dose of study drug up to safety follow-up visit (up to Week 12)	0.00% 0/54 • From first dose of study drug up to safety follow-up visit (up to Week 12)	33.3% 1/3 • From first dose of study drug up to safety follow-up visit (up to Week 12)