A phase II study to assess vismodegib in the treatment of idiopathic pulmonary fibrosis

• Register: EUCTR
• Last refreshed on: 7 September 2015
• Main ID: EUCTR2014-000963-42-DE
• Date of registration: 13/08/2014
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: A phase II study to assess vismodegib in the treatment of idiopathic pulmonary fibrosis
• Scientific title: A randomized, double-blind, placebo-controlled, phase II study to assess the efficacy and safety of oral vismodegib for the treatment of idiopathic pulmonary fibrosis - ISLAND
• Date of first enrolment: 01/10/2014
• Target sample size: 129
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000963-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Chile, France, Germany, Israel, Italy, Korea, Republic of, Mexico, New Zealand, Peru, Spain, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
- Age > or equal to 40 years at Visit 1
- Have a diagnosis of IPF based upon the ATS/ERS/JRS/ALAT consensus statement on IPF (Raghu et al. 2011) within the previous 5 years from time of screening and confirmed at baseline Have a central review assessment of HRCT performed during the screening period or < or equal to 12 months prior to the start of screening
- Patients from countries where a treatment is licensed/approved for IPF must additionally meet at least one of the following criteria to be eligible;
- Be unable to access a licensed therapy for IPF
- Treatment with a licensed therapy/therapies has been stopped for lack of efficacy or because of safety/tolerability reasons (a period of washout will be required; refer to Section 4.1.2)
- Be unwilling to be treated with a licensed/approved therapy and after having reviewed all available treatment options, the investigator and patient consider enrollment into the study appropriate
- FVC = 40% and < or equal to 90% of predicted at screening
- Stable baseline lung function as evidenced by a difference of < 10% in absolute FVC measurements (in liters) between screening and Day 1/Visit 2 prior to randomization
- DLco > or equal to 25% of predicted at screening
- Adequate hematopoietic capacity, defined as the following:
- Hemoglobin > 8.5 g/dL
- ANC > or equal to 1000/microlitre
- Platelet count > or equal to 75,000/microlitre
- Adequate liver function, defined as the following:
- AST and ALT < or equal to 3 times the upper limit of normal (ULN)
- Total bilirubin < or equal to 1.5 x ULN or < 3 x ULN for patients with documented Gilbert syndrome
- Women of childbearing potential must use two methods of acceptable contraception including one highly effective method and a barrier method as directed by their physician during treatment for 7 months after completion of study treatment (or as per local requirement)
- Male patients must agree to remain abstinent or use a condom, even after a vasectomy, during sexual intercourse with female partners while being treated with vismodegib/placebo, and for 2 months after completion of study treatment.
- Agreement not to donate blood or blood products during the study and for at least 7 months (or as per local requirements) after the last dose of study treatment

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 64
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion criteria:
- Prior treatment with vismodegib or any Hh pathway inhibitor
- Evidence of other known causes of ILD
- Hospitalization due to an exacerbation of IPF within 4 weeks prior to, or during, screening
- Lung transplant expected within 12 months of screening
- Evidence of clinically significant lung disease other than IPF
- Substantial emphysema on HRCT with degree of emphysema greater than fibrosis
- Class IV New York Heart Association chronic heart failure or historical evidence of left ventricular ejection fraction < 35%
- Known current malignancy or current evaluation for a potential malignancy
- Known immunodeficiency, including but not limited to HIV infection



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Idiopathic pulmonary fibrosis
MedDRA version: 17.0 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Trade Name: Erivedge
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: vismodegib
CAS Number: 879085-55-9
Other descriptive name: VISMODEGIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: - Change in diffusion capacity of the lung for carbon dioxide (DLco)
- Change in pulmonary function: annualized rate of change in FVC
- Progression-free survival
- Acute IPF exacerbations
- Change in quality of life measurement

Main Objective: - Change in pulmonary function (FVC% predicted) from baseline to week 52

Timepoint(s) of evaluation of this end point: - from baseline to week 52

Primary end point(s): - Change in pulmonary function (FVC% predicted)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. from baseline to week 52
2. from baseline to week 52
3. from randomization to the first occurrence of any of the following:
• Death from any cause
• Non-elective hospitalization from any cause
• =10% decline in FVC (L) (relative change) from baseline
4. from randomization to first event
5. from baseline to week 52

Secondary end point(s): 1. Change in DLco % predicted
2. Annualized rate of change in FVC (liters)
3. Progression free survival
4. Acute IPF exacerbations
5. Change in IPF-specific health-related quality of life

Secondary ID(s)

GB29298

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd.