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A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Phase 3 trial testing VX-445/TEZ/IVA in Cystic Fibrosis in 405 participants. Completed in 24 April 2019.
| Lead sponsor | Vertex Pharmaceuticals Incorporated |
|---|---|
| Phase | Phase 3 |
| Status | Completed |
| Study type | INTERVENTIONAL |
| Allocation | randomized |
| Design | parallel |
| Masking | quadruple |
| Primary purpose | treatment |
| Enrollment | 405 |
| Start date | 15 June 2018 |
| Primary completion | 24 April 2019 |
| Estimated completion | 24 April 2019 |
| Sites | 115 locations across France, Italy, Netherlands, Greece, Belgium, Austria, Sweden, United Kingdom |
Vertex Pharmaceuticals Incorporated — full company profile →
12 and older, any sex, with Cystic Fibrosis. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -0.2 | ± 0.6 |
| VX-445/TEZ/IVA TC | 13.6 | ± 0.6 |
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -0.4 | ± 0.5 |
| VX-445/TEZ/IVA TC | 13.9 | ± 0.6 |
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | 113 | |
| VX-445/TEZ/IVA TC | 41 |
Sweat samples were collected using an approved collection device.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -0.4 | ± 0.9 |
| VX-445/TEZ/IVA TC | -42.2 | ± 0.9 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -2.7 | ± 1.0 |
| VX-445/TEZ/IVA TC | 17.5 | ± 1.0 |
BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
| Group | Value | 95% CI |
|---|---|---|
| Placebo | 0.09 | ± 0.07 |
| VX-445/TEZ/IVA TC | 1.13 | ± 0.07 |
Sweat samples were collected using an approved collection device.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | 0.1 | ± 1.0 |
| VX-445/TEZ/IVA TC | -41.2 | ± 1.0 |
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.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | -1.9 | ± 1.1 |
| VX-445/TEZ/IVA TC | 18.1 | ± 1.1 |
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | NA | NA – NA |
| VX-445/TEZ/IVA TC | NA | NA – NA |
BMI was defined as weight in kg divided by height in m\^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.
| Group | Value | 95% CI |
|---|---|---|
| Placebo | 0.04 | ± 0.05 |
| VX-445/TEZ/IVA TC | 0.34 | ± 0.05 |
| Group | Value | 95% CI |
|---|---|---|
| Placebo | 0.5 | ± 0.2 |
| VX-445/TEZ/IVA TC | 3.4 | ± 0.2 |
| Group | Value | 95% CI |
|---|---|---|
| Placebo | 193 | |
| VX-445/TEZ/IVA TC | 188 |
| Group | Value | 95% CI |
|---|---|---|
| Placebo | 42 | |
| VX-445/TEZ/IVA TC | 28 |
Time frame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | Placebo | VX-445/TEZ/IVA TC |
|---|---|---|---|
| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | — | — |
| Influenza | Infections and infestations | — | — |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | — | — |
| Rash | Skin and subcutaneous tissue disorders | — | — |
| Atypical mycobacterial lower respiratory tract infection | Infections and infestations | — | — |
| Coccidioidomycosis | Infections and infestations | — | — |
| Genital herpes simplex | Infections and infestations | — | — |
| Lung infection | Infections and infestations | — | — |
| Pneumonia | Infections and infestations | — | — |
| Viral sinusitis | Infections and infestations | — | — |
| Diaphragmatic paralysis | Respiratory, thoracic and mediastinal disorders | — | — |
| Nasal polyps | Respiratory, thoracic and mediastinal disorders | — | — |
| Painful respiration | Respiratory, thoracic and mediastinal disorders | — | — |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | — | — |
| Pneumothorax spontaneous | Respiratory, thoracic and mediastinal disorders | — | — |
| Hypersensitivity vasculitis | Skin and subcutaneous tissue disorders | — | — |
| Rash pruritic | Skin and subcutaneous tissue disorders | — | — |
| Small intestinal obstruction | Gastrointestinal disorders | — | — |
| Abdominal pain upper | Gastrointestinal disorders | — | — |
| Distal intestinal obstruction syndrome | Gastrointestinal disorders | — | — |
| Cholangitis | Hepatobiliary disorders | — | — |
| Gallbladder enlargement | Hepatobiliary disorders | — | — |
| Hypertransaminasaemia | Hepatobiliary disorders | — | — |
| Portal hypertension | Hepatobiliary disorders | — | — |
| Back pain | Musculoskeletal and connective tissue disorders | — | — |
| Reaction | System | Placebo | VX-445/TEZ/IVA TC |
|---|---|---|---|
| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | — | — |
| Cough | Respiratory, thoracic and mediastinal disorders | — | — |
| Sputum increased | Respiratory, thoracic and mediastinal disorders | — | — |
| Headache | Nervous system disorders | — | — |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | — | — |
| Nasopharyngitis | Infections and infestations | — | — |
| Diarrhoea | Gastrointestinal disorders | — | — |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | — | — |
| Upper respiratory tract infection | Infections and infestations | — | — |
| Abdominal pain | Gastrointestinal disorders | — | — |
| Alanine aminotransferase increased | Investigations | — | — |
| Fatigue | General disorders | — | — |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | — | — |
| Blood creatine phosphokinase increased | Investigations | — | — |
| Aspartate aminotransferase increased | Investigations | — | — |
| Pyrexia | General disorders | — | — |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | — | — |
| Rash | Skin and subcutaneous tissue disorders | — | — |
| Productive cough | Respiratory, thoracic and mediastinal disorders | — | — |
| Nausea | Gastrointestinal disorders | — | — |
| Rhinitis | Infections and infestations | — | — |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | — | — |
| Influenza | Infections and infestations | — | — |
| Vomiting | Gastrointestinal disorders | — | — |
| Constipation | Gastrointestinal disorders | — | — |
| Sinusitis | Infections and infestations | — | — |
| Bacterial test positive | Investigations | — | — |
| Blood bilirubin increased | Investigations | — | — |
Most-reported serious reactions: Infective pulmonary exacerbation of cystic fibrosis, Influenza, Haemoptysis, Rash, Atypical mycobacterial lower respiratory tract infection, Coccidioidomycosis, Genital herpes simplex, Lung infection.
Data from ClinicalTrials.gov NCT03525444 adverse events section.
This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).
8 peer-reviewed publications reference this trial (live from Europe PMC):
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