Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as VX-809, LUM
Lumacaftor · 13 trials · 4 indications
Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
AE: any untoward medical occurrence in a participant during the study; event does not necessarily have a causal relationship with treatment. This includes any newly occurring event/previous condition that has increased in severity/frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. TEAEs: AEs that started/ worsened on/after the start of study drug through the Safety Follow up Visit (4 weeks after the last dose of study drug). Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
AE: as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or newly developed at or after initial dosing of study drug was considered treatment-emergent.
AE: as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or newly developed at or after initial dosing of study drug was considered treatment-emergent.
The AUCtau is the area under the concentration versus time curve from time 0 to time tau, where tau is the time at the end of dosing interval.
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first study drug dose to Week 26 were considered treatment-emergent.
Absolute change from baseline at Week 24 was assessed as the average treatment effect at Week 16 and at Week 24. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years.
AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent. AE includes serious AEs (SAEs) as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21).
Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56).
AEs and SAEs are defined in Outcome Measure 1.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Hankinson method.
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. Serious adverse event (SAE) (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent.
Blood samples drawn during the study will be analyzed to measure the PK parameters, such as concentration, exposure and half-life of VX-809 and its metabolite.
Blood samples drawn during the study will be analyzed to measure the PK parameters, such as concentration, exposure and half-life of VX-770 and its metabolites.
| Arm | Type | Description |
|---|---|---|
| LUM/IVA | EXPERIMENTAL | Fixed-dose combination with lumacaftor (LUM) 200 mg every 12 hours (q12h)/ ivacaftor (IVA) 250 mg q12h |
| Placebo | PLACEBO_COMPARATOR | Matching placebo q12h |
| Lumacaftor/Ivacaftor combination | EXPERIMENTAL | Lumacaftor 400 milligram (mg) and ivacaftor 250 mg combination tablet orally twice daily for 24 weeks. |
| Arm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12h | EXPERIMENTAL | Participants who received lumacaftor (LUM, VX-809) 600 milligram (mg) plus ivacaftor (IVA, VX-770) 250 mg fixed-dose combination (FDC) tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening, in the previous study VX12-809-103 or VX12-809-104, and will receive the same treatment in this study VX12-809-105 up to Week 96. |
| Arm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12h | EXPERIMENTAL | Participants who received placebo matched to LUM and IVA tablet in the previous study VX12-809-103 or VX12-809-104, and will receive LUM 600 mg plus IVA 250 mg FDC tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening in this study VX12-809-105 up to Week 96. |
| Arm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12h | EXPERIMENTAL | Participants who received LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in the previous study VX12-809-103 or VX12-809-104, and will receive the same treatment in this study VX12-809-105 up to Week 96. |
| Arm 4 Part A: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h | EXPERIMENTAL | Participants who received placebo matched to LUM and IVA tablet in the previous study VX12-809-103 or VX12-809-104, and will receive LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in this study VX12-809-105 up to Week 96. |
| Arm 5 Part A: Observational Cohort | NO_INTERVENTION | Participants who received either LUM 600 mg plus IVA 250 mg FDC tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening OR LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening OR placebo matched to LUM and IVA in the morning and evening, in the previous study VX12-809-103 or VX12-809-104, and will be observed (will not receive study drug) in this study VX12-809-105 for up to 2 years. |
| Arm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12h | EXPERIMENTAL | Participants who received LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in Cohort 4 of the previous study VX09-809-102, and will receive the same treatment in this study VX12-809-105 up to Week 96. |
| Arm 7 Part B: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h | EXPERIMENTAL | Participants who received placebo matched to LUM and IVA tablet in Cohort 4 of the previous study VX09-809-102, and will receive LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in this study VX12-809-105 up to Week 96. |
| Lumacaftor/Ivacaftor (LUM/IVA) | EXPERIMENTAL | Part A Cohort 1: Participants aged 6 through 8 years will receive LUM 200 milligram (mg) in fixed-dose combination with IVA 250 mg orally every 12 hours (q12h) for 14 days. Part A Cohort 2: Participants aged 9 through 11 years will receive LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days. Part B: Participants aged 6 through 11 years will receive LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 24 weeks. |
| LUM 600 mg qd/IVA 250 mg q12h | EXPERIMENTAL | LUM 600 milligram (mg) plus IVA 250 mg fixed-dose combination (FDC) tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24. |
| LUM 400 mg q12h/ IVA 250 mg q12h | EXPERIMENTAL | LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24. |
| Cohort 1: Placebo | PLACEBO_COMPARATOR | Participants homozygous (HO) for the F508del-CF transmembrane conductance regulator gene (CFTR) mutation received lumacaftor matched placebo once daily (qd) (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo every 12 hours (q12h) (Day 15 through Day 21). |
| Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h | EXPERIMENTAL | Participants homozygous for the F508del-CFTR mutation received 200 milligram (mg) of lumacaftor (LUM) qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor (IVA) q12h (Day 15 through Day 21). |
| Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h | EXPERIMENTAL | Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21). |
| Cohort 2 and 3: Placebo (HO and HE) | PLACEBO_COMPARATOR | Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56). |
| Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO) | EXPERIMENTAL | Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). |
| Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO) | EXPERIMENTAL | Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). |
| Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE) | EXPERIMENTAL | Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). |
| Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO) | EXPERIMENTAL | Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). |
| Cohort 4: Placebo | PLACEBO_COMPARATOR | Participants heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). |
| Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h | EXPERIMENTAL | Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56). |
| VX-809, 25 mg | EXPERIMENTAL | VX-809, 25 milligram (mg) capsule orally once daily for 28 days. |
| VX-809, 50 mg | EXPERIMENTAL | VX-809, 50 mg capsule orally once daily for 28 days. |
| VX-809, 100 mg | EXPERIMENTAL | VX-809, 100 mg capsule orally once daily for 28 days. |
| VX-809, 200 mg | EXPERIMENTAL | VX-809, 200 mg capsule orally once daily for 28 days. |
| Part A | EXPERIMENTAL | A single dose of 2 fixed-dose combination tablets of 200mg lumacaftor/125mg ivacaftor (total of 400mg lumacaftor/250mg ivacaftor) in the fed state and fasted state with a 14 day washout period in between each dosing occasion |
| Part B | EXPERIMENTAL | A single dose of 3 fixed-dose combination tablets of 200mg lumacaftor/83mg ivacaftor (total of 600mg lumacaftor and 250mg ivacaftor) in the fed with a 14 day washout period in between dosing occasions |
| Treatment Group (Cohort 1) | EXPERIMENTAL | Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and ciprofloxacin through Day 21. |
| Treatment Group (Cohort 2) | EXPERIMENTAL | Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and itraconazole through Day 21. |
| Treatment Group (Cohort 3) | EXPERIMENTAL | Subjects will take lumacaftor in combination with ivacaftor for 14 days. Beginning on Day 15, subjects will take lumacaftor in combination with ivacaftor and rifampin through Day 24. |
| Treatment Group (Cohort 4) | EXPERIMENTAL | Subjects will take a single dose of lumacaftor in combination with ivacaftor on 3 occasions separated by 7 days. |
| Treatment Arm | EXPERIMENTAL | Subjects randomized to study drug will take VX-809 for 14 days followed by a 14 day washout. Next subjects will take VX-770 for 14 days followed by a 14 day washout. Lastly, subjects will take both VX-809 and VX-770 for 14 days. |
| Placebo Arm | PLACEBO_COMPARATOR | Subjects randomized to placebo will take VX-809 placebo for 14 days followed by a 14 day washout. Next subjects will take VX-770 placebo for 14 days followed by a 14 day washout. Lastly, subjects will take both VX-809 and VX-770 placebo for 14 days. |
| Treatment Period 1 | EXPERIMENTAL | - |
| Treatment Period 2 | EXPERIMENTAL | - |
| Treatment Period 3 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| VX-809 | DRUG | - |
| Placebo | DRUG | - |
| VX-770 | DRUG | - |
| Lumacaftor | DRUG | - |
| Ivacaftor | DRUG | - |
| Lumacaftor Plus Ivacaftor Combination | DRUG | Fixed dose combination tablet, oral use |
| Lumacaftor Placebo | DRUG | Matching placebo tablet. |
| Ivacaftor Placebo | DRUG | Matching placebo tablet. |
| moxifloxacin hydrochloride | DRUG | - |
| Ciprofloxacin | DRUG | 750 mg taken every 12 hours |
| Itraconazole | DRUG | 200mg taken once daily |
| Rifampin | DRUG | 600mg taken once daily |
| VX-809 placebo | DRUG | capsule, taken once daily |
| VX-770 placebo | DRUG | tablet, taken once every 12 hours |
| VX-809 & VX-770 | DRUG | VX-809 capsule, once daily, and VX-770 tablets, once every 12 hours, for 14 days |
Inclusion Criteria: * Subjects who weigh ≥15 kg without shoes a the Screening Visit * Subjects with confirmed diagnosis of CF at the Screening Visit. * Subjects who are homozygous for the F508del CFTR mutation * Subjects with ppFEV1 of ≥70 percentage points adjusted for age, sex, and height * Subje...
Top 6 of 7 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Vertex Pharmaceuticals Incorporated | VRTX | 8 | PHASE3 | Alyftrek, Trikafta, Ivacaftor, VX-581, VX-272 |
| BiomX Inc. | PHGE | 1 | PHASE2 | BX004 |
| 4D Molecular Therapeutics, Inc. | FDMT | 1 | PHASE2 | 4D-710 |
| Arcturus Therapeutics Holdings, Inc. | ARCT | 1 | PHASE2 | ARCT-032 |
| Krystal Biotech, Inc. | KRYS | 1 | PHASE1 | KB407 |
| Roivant Sciences Ltd. | ROIV | 1 | PHASE1 | SP-101 |
Lumacaftor is used in combination with ivacaftor to treat cystic fibrosis in people whose CFTR mutation includes the F508del mutation. It is studied in patients homozygous for F508del and in those who are homozygous or heterozygous for the F508del-CFTR mutation. It is a small molecule CFTR stabilizer.
Lumacaftor targets the CFTR protein and acts as a CFTR stabilizer. By stabilizing the mutant CFTR protein, it aims to improve its function at the cell surface. It is used in combination with ivacaftor, which is a CFTR potentiator.
Lumacaftor is being developed by Vertex Pharmaceuticals Incorporated, which trades under the ticker symbol VRTX. The company is responsible for the clinical development of lumacaftor in combination with ivacaftor for cystic fibrosis.
Lumacaftor is in Phase 3 clinical development. It is an investigational agent and has been studied in completed Phase 3 trials, including a rollover study and a study in patients with advanced lung disease. It is not described as approved.
Lumacaftor has been evaluated in completed clinical trials including NCT02390219, a Phase 3 study in patients 12 years and older with advanced lung disease, and NCT01931839, a Phase 3 rollover study in patients with cystic fibrosis. Earlier Phase 1 studies include NCT01910415 and NCT01899105.