Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation

Vertex Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

Treatments: Drug: Lumacaftor Placebo; Drug: Lumacaftor; Drug: Ivacaftor; Drug: Ivacaftor Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01225211

VX09-809-102

2010-020413-90 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.

Enrollment: 312 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female participants with confirmed diagnosis of CF
• Must have the F508del-CFTR mutation on at least 1 allele.
• FEV1 greater than equal (>=) 40% of predicted normal for age, gender, and height (Knudson standards)(Cohort 1, 2, and 3); FEV1 40-90% of predicted normal for age, gender, and height (Hankinson standards (Cohort 4)
• Participant of child-bearing potential and who are sexually active must meet the contraception requirements

Exclusion criteria

• History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the participant (e.g., cirrhosis with portal hypertension).
• An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days (Cohort 1, 2, and 3) or 28 days (Cohort 4) before receiving the first dose of study drug.
• History of solid organ or hematological transplantation.
• History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine, and opiates.
• Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout
• Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception
• Participants enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3
• Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit
• Heterozygous participants who participated in Cohort 2 and meet the eligibility criteria for Cohort 4 may participate in Cohort 4
• Evidence of lens opacity or cataract as determined by the ophthalmologic examination (Cohort 4 only)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

---

312 participants in 10 patient groups, including a placebo group

Cohort 1: Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Lumacaftor Placebo

Drug: Ivacaftor Placebo

Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h

Experimental group

Description:

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).

Treatment:

Drug: Ivacaftor

Drug: Lumacaftor

Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h

Experimental group

Description:

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).

Treatment:

Drug: Ivacaftor

Drug: Lumacaftor

Cohort 2 and 3: Placebo (HO and HE)

Placebo Comparator group

Description:

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).

Treatment:

Drug: Lumacaftor Placebo

Drug: Ivacaftor Placebo

Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO)

Experimental group

Description:

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).

Treatment:

Drug: Ivacaftor

Drug: Lumacaftor

Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO)

Experimental group

Description:

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).

Treatment:

Drug: Ivacaftor

Drug: Lumacaftor

Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE)

Experimental group

Description:

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).

Treatment:

Drug: Ivacaftor

Drug: Lumacaftor

Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO)

Experimental group

Description:

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).

Treatment:

Drug: Ivacaftor

Drug: Lumacaftor

Cohort 4: Placebo

Placebo Comparator group

Description:

Participants heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 1 through Day 56).

Treatment:

Drug: Lumacaftor Placebo

Drug: Ivacaftor Placebo

Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h

Experimental group

Description:

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).

Treatment:

Drug: Ivacaftor

Drug: Lumacaftor