Safety and Efficacy of QAX576 in Patients With Progressive Idiopathic Pulmonary Fibrosis (IPF)

• Register: EUCTR
• Last refreshed on: 20 May 2013
• Main ID: EUCTR2010-020688-18-GB
• Date of registration: 28/01/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Safety and Efficacy of QAX576 in Patients With Progressive Idiopathic Pulmonary Fibrosis (IPF)
• Scientific title: A randomized, double-blind, placebo-controlled, multipledose, exploratory proof of concept study to assess the safety, tolerability, efficacy, pharmacodynamics and pharmacokinetics of QAX576 in patients with rapidly progressive idiopathic pulmonary fibrosis
• Date of first enrolment: 29/06/2011
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020688-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

United Kingdom

Contacts

• Name: Medical Information Services
• Affiliation: Novartis Pharmaceuticals UK Ltd

• Name: Medical Information Services
• Affiliation: Novartis Pharmaceuticals UK Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent must be obtained before any participation in the study.
2. Male or female subjects of =18 years of age to =80 years of age.
3. Diagnosis of IPF, based on an appropriate clinical definition of IPF as detailed in the
(ATS/ERS/JRS/ALAT statement: Idiopathic Pulmonary Fibrosis:Evidence-based Guidelines for diagnosis and management (Raghu G et al 2011)
Diagnosis must be confirmed by diagnostic HRCT or lung biopsy
4. A 6-minute walk test (6MWT) distance =50 meters at Screening (use of supplemental oxygen allowed).
5. Forced Vital Capacity FVC) =50% of predicted at Screening.
6. Diffusing capacity for carbon monoxide (DLco) uncorrected =30 of predicted at
Screening
7. Body mass index (BMI) must be within the range 18 to 40
8. Subjects should be able to communicate well with the investigator and to understand and comply with the requirements of the study.
9. Female patients must be of non-childbearing potential:
Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In the case of oophorrectomy alone, only when the reproductive status of the women has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Smokers (use of tobacco products in the previous 3 months). Urine cotinine levels will be measured during screening for all subjects. Smokers will be defined as any subject who reports tobacco use or has a urine cotinine levels in the range defined as ‘smokers’ per the local lab.
2. Participation in any therapeutic trial within four (4) weeks prior to initial dosing or
longer if required by local regulations, and for any other limitation of participation based on local regulations. For trials involving study medication, subjects dosed with active study medication should not be screened until = five half-lives of the study medication have passed (or as guided by local regulations if longer).
3. Participation in an IPF therapeutic trial in the 8 weeks (or 16 weeks in the case of an experimental monoclonal antibody) prior to Screening.
4. Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial
dosing, or longer if required by local regulation.
5. A past medical history of clinically significant ECG or cardiac abnormalities (NB, cases of right ventricular hypertrophy, secondary pulmonary hypertension or right bundle branch block should be discussed with the sponsor).
6. FEV1/FVC ratio < 0.6 at screening (pre or post-bronchodilator).
7. Lung residual volume > 120% predicted at Screening.
8. High-Resolution Computed Tomography (HRCT) showing only ground glass infiltrates without other typical features of pulmonary fibrosis such as basilar predominant reticular infiltrates, honeycombing, and traction bronchiectasis, unless there is lung biopsy proven evidence of predominant UIP.
9. Subjects who within the preceding 6 months have traveled to or emigrated from an area with endemic schistosomiasis, including but not limited to Southeast and Southwest Asia, South America and Africa, or who have had a prior diagnosis of schistosomiasis must have 3 negative stool ova and parasite studies.
10. Any condition other than pulmonary fibrosis which in the opinion of the investigator is
likely to result in the death of the patient within the next year.
11. History of unstable or deteriorating cardiac or neurological disease.
12. Chronic treatment for IPF with the following drugs at randomization. If a subject is being treated with a prohibited therapy and the study investigator feels it is appropriate to discontinue the therapy, the duration of the washout prior to andomization will be discussed with the Sponsor on a case-by-case basis.
• Oral corticosteroids (> 20 mg/day of prednisone or equivalent),
• Immunosuppressive or cytotoxic drugs including cyclophosphamide and
azathioprine,
• Antifibrotic drugs including pirfenidone, D penicillamine, colchicine, TNFa
blocker, imatinib and interferon ?,
• Chronic use of N-acetylcysteine prescribed for IPF (> 600 mg/day).
13. Exposure to human therapeutic monoclonal antibodies within the 3 months prior to the first dose or known hypersensitivity to monoclonal antibodies or human plasma products.
14. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
15. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
16. History of drug or alcohol abuse within the 12 months prior to dosing.
17. Nursing mothers.
18. Subjects should not be enrolled if the investigator feels they are likely to require a lung transplant in the next 4 months.
19. Subjects who are participating in a pulmonary rehabilitat

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

Health Condition(s) or Problem(s) studied

Patients with rapidly progressive idiopathic pulmonary fibrosis
MedDRA version: 14.1 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Code: QAX576
Pharmaceutical Form: Powder and solvent for solution for infusion
Current Sponsor code: QAX576
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Powder and solvent for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Primary endpoint:
• The primary efficacy endpoint is change from baseline in FVC measurement at 52 weeks as assessed at each clinical visit post-baseline.
Additional details are included in section 9.4 of the clinical study protocol

Secondry endpoints:
• all-cause mortality, time to clinical worsening defined as 10% fall in FVC or 15% fall in DLco, lung transplant or lung disease (IPF)-related death.
• incidence of exacerbation of IPF.
• lung volume (TLC, RV, FRV) and diffusing capacity of the lung for carbon monoxide (DLco).
• 6 minute walk distance, pulse oximetry and heart rate recovery.
• progression of fibrosis in the lungs as measured by Quantitative High Resolution
Computerized Tomography (HRCT).
• patient reported symptoms.

Main Objective: • To evaluate the safety and tolerability of multiple intravenous dosing of QAX576 in
patients with IPF
• To evaluate the effect of multiple intravenous dosing of QAX576 on lung function
assessed by FVC at 1 year as compared to baseline

Secondary Objective: 1. To evaluate the effect of multiple intravenous dosing of QAX576 on additional measures of clinical efficacy, including:
• all-cause mortality, time to clinical worsening defined as 10% fall in FVC or 15% fall
in DLco, lung transplant or lung disease (IPF)-related death.
• incidence of exacerbation of IPF.
• lung volume (TLC, RV, FRV) and diffusing capacity of the lung for carbon monoxide
(DLco).
• 6 minute walk distance, pulse oximetry and heart rate recovery.
• progression of fibrosis in the lungs as measured by Quantitative High Resolution
Computerized Tomography (HRCT).
• patient reported symptoms.
2. To evaluate the pharmacokinetics of QAX576 in this patient population.

Secondary ID(s)

CQAX576A2203

Source(s) of Monetary Support

Novartis Pharma Services AG