Study of pharmacodynamics, pharmacokinetics, safety and tolerability of VAY736 in patients with idiopathic pulmonary fibrosis

• Register: EUCTR
• Last refreshed on: 10 August 2021
• Main ID: EUCTR2017-002667-17-IT
• Date of registration: 13/02/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: Study of pharmacodynamics, pharmacokinetics, safety and tolerability of VAY736 in patients with idiopathic pulmonary fibrosis
• Scientific title: A subject-, investigator-, and sponsor-blinded, randomized, placebo-controlled, multicenter study to investigate efficacy, safety, and tolerability of VAY736 in patients with idiopathic pulmonary fibrosis - Study of pharmacodynamics,pharmacokinetics, safety and tolerability of VAY736 in patients with idiop
• Date of first enrolment: 20/09/2018
• Target sample size: 84
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002667-17
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, France, Germany, Ireland, Italy, United Kingdom, United States

Contacts

• Name: Medical Information Department
• Affiliation: Novartis Ireland Limited

• Name: Medical Information Department
• Affiliation: Novartis Ireland Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent must be obtained before any assessment is performed.
2. Male and female subjects 40 to 80 years of age inclusive
3. A diagnosis of definite or probable IPF within 5 years of the screening visit, as defined by the ATS/ERS/JRS/ALAT Diagnostic Guidelines (Raghu et al 2011)
4. Seropositive at screening for at least one of the following auto-antibodies: RF, ANA, anti-dsDNA, anti-CCP, Scl-70, SSA (anti-Ro), SSB (anti-La), anti-RNP, anti-Smith, Jo-1, PL-7, PL-12, EJ, OJ, SRP, Ku, Mi-2, anti-PM/Scl;
OR
Presence of hilar/mediastinal adenopathy (>1cm in short-axis diameter), identified by screening HRCT scan of the chest
5. FVC 50-90% predicted (inclusive)
6. DLCO, corrected for hemoglobin, 30-79% predicted (inclusive)
7. FEV1/FVC >70%
8. Unlikely to die from cause other than IPF within the next 3 years, in the opinion of the investigator
9. Unlikely to undergo lung transplantation during this trial
10. Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Other protocol-defined inclusion/exclusion criteria may apply
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 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1. Emphysema > fibrosis on screening HRCT (must be confirmed by central reader)
2. Active viral, bacterial or other infections requiring systemic treatment at the time of screening or enrollment, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms
3. History of major organ, hematopoietic stem cell or bone marrow transplant
4. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (e.g., mAb of IgG1 class) or to any of the constituents of the study drug (sucrose, L-Arginine hydrochloride, L-histidine, polysorbate 80, hydrochloric acid)
5. Receipt of live/attenuated vaccine within a 2 month period before baseline
6. History of primary or secondary immunodeficiency, including a positive Human Immunodeficiency Virus (HIV) (Enzyme-linked Immunosorbent Assay (ELISA) and Western blot) test result
7. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin, in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
8. Any one of the following screening values of complete blood count laboratory values: Hemoglobin levels below 8.0 g/dL; Total leukocyte count less than 2,000/µL; Platelets <100.0 x 109/L; Absolute neutrophil count (ANC) <1.5 x 109/L
9. Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes), psychiatric or additional physical condition that the Investigator feels may jeopardize the patient in case of participation in this study
10. Positive hepatitis B surface antigen (HBsAg) with concurrent negative hepatitis B surface antibody (anti-HBs); or positive total hepatitis B core antibody (anti-HBc) with concurrent negative anti-HBs; or positive hepatitis C antibody (anti-HCV); i.e., any acute or chronic infection with hepatitis B or hepatitis C
11. Evidence of active or latent tuberculosis (TB) infection, as determined by Quantiferon test (after anti-TB treatment, patients with history of or latent TB may become eligible according to national guidelines)

Other protocol-defined inclusion/exclusion criteria may apply


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

Health Condition(s) or Problem(s) studied

Idiopathic pulmonary fibrosis
MedDRA version: 20.0 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

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

Intervention(s)

Product Code: VAY736
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: not established
Other descriptive name: VAY736
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: Impact of VAY736 on survival and disease progression.

Other protocol-defined secondary objectives may apply

Timepoint(s) of evaluation of this end point: end of treatment epoch (48 weeks of treatment)

Main Objective: To assess the efficacy of VAY736 in patients with idiopathic pulmonary fibrosis

Primary end point(s): Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC).

Secondary Outcome(s)

Secondary end point(s): All-Cause mortality; Progression-free survival (PFS); Disease progression; Composite Endpoint; Change from baseline to end of treatment epoch (Week 48) in Diffusing Capacity of the Lungs (DLCO); Change from baseline to the end of treatment epoch (Week 48) in 6-minute walk test and in distance-saturation product; Change from baseline to the end of treatment epoch (Week 48) in resting oxygen saturation (on room air); Immunogenicity of VAY736; To assess the pharmacokinetics Cmin,ss of VAY736 after multiple s.c. doses; Idiopathic Pulmonary Fibrosis (IPF) -related Mortality; Change from baseline to end of treatment epoch (Week 48) in Total Lung Capacity (TLC)
Other protocol defined endpoints may apply

Timepoint(s) of evaluation of this end point: across the 48 weeks of treatment and at the end of study

Secondary ID(s)

CVAY736X2207

NCT03287414

2017-002667-17-GB

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 17/09/2018
Contact: