|Principal Investigator: Mary Scholand|
|Keywords: IPF , Pulmonary Fibrosis , Idiopathic Pulmonary Fibrosis , ILD , Interstitial Lung Disease , Galactic||Department: Pulmonary|
|IRB Number: 00119951|
|Sub Specialties: Pulmonary Fibrosis|
|Recruitment Status: Recruiting|
• Efficacy of TD139 in SoC2 IPF subjects (not currently treated with pirfenidone/Nintedanib) by assessing the annual rate of decline in Forced Vital Capacity (FVC; expressed in mL over 52 weeks)
Key Secondary Objectives
• Efficacy of TD139 in IPF subjects by assessing the annual rate of decline in FVC in the SoC1 group and for all subjects combined.
• Proportion of subjects with an absolute decline from baseline in FVC % pred of >10% at w52 both in the SoC1 & SoC2 groups independently and for all subjects combined.
• Time to first hospitalization (all-cause, respiratory-related causes and/or caused by acute exacerbation of IPF) both in the SoC1 & SoC2 groups independently and for all subjects combined.
• Time to death (all-cause, respiratory-related causes and/or caused by IPF) both in the SoC1 & SoC2 groups independently and for all subjects combined. Additional secondary and exploratory efficacy variables with bearing on the efficacy of TD139 (e.g. QoL) are described in detail in the Main Criteria and Evaluation and Analyses below)
• Proportion of subjects with an absolute decline from baseline in FVC % pred of >5% at w52
• Change in 6-minute walk test (6MWT) distance over 52 weeks
• Change in diffusion capacity of the lung for carbon monoxide (DLCO)
• Dyspnoea assessment by University of California San Diego - Shortness of Breath Questionnaire (UCSD - SOBQ)
• HRQoL as assessed by Short Form Survey (SF-36) and the St. George`s Respiratory Questionnaire (SGRQ) Total Score worsening
• Percentage of subjects with Adverse Events (AE) or Serious Adverse Events (SAE) over 52 weeks
• Time to initiation of pirfenidone or nintedanib treatment for SoC2 subjects
• Time to termination of pirfenidone or nintedanib treatment for SoC1 subjects
• Change in FVC expressed in mL over 52 weeks for subjects who have never been treated with pirfenidone or nintedanib
Biomarkers: Change from baseline of selected biomarkers. These may include but are not limited to: YKL-40, PAI-1, PDGF-BB, MCP-1, CCL-18, Gal-3, markers of collagen metabolism.
1. Male and female subjects aged ≥ 40 years of age with a diagnosis of IPF established during the previous three years according to ATS/ERS/IRS/ALAT and Fleischner criteria [1-3]. An historical diagnostic HRCT scan assessed according the ATS/ERS/IRS/ALAT and Fleischner criteria must be available from within the 12 months prior to screening. Note: If a historical scan (within 12 months) is not available, a HRCT scan can be performed (according to local IPF protocols) during screening to determine eligibility. All diagnostic HRCTs will be subject to central reading for confirmation.
2. Lung function parameters as follows:
a. FVC > 45% of the predicted value at screening
b. DLCO (corrected for Hb) of 30% to 79% of the predicted value at screening.
3. Any existing SoC treatment (e.g. pirfenidone or nintedanib in the SoC1 group, but excluding prohibited medicines) must be deemed as stable (i.e. dosing regimen, and tolerability) by the PI/treating physician before randomization into the study.
4. Subjects must sign and date a written, informed consent form and any required authorization prior to initiation of any study procedures.
Subjects meeting any of the following exclusion criteria are not to be enrolled in the study/randomized to treatment:
1. Currently has significant airways obstruction: FEV1/FVC ratio of < 0.7 at screening
2. Has clinical evidence of active infection, including, but not limited to, bronchitis, pneumonia, sinusitis, urinary tract infection, and cellulitis.
3. Has a history of malignancy within the last 2 years with the exception of basal cell carcinoma, squamous cell carcinoma of the skin (localised, treated or cured), chronic lymphocytic leukaemia (under observation) and prostate cancer requiring androgens, localised treatment (minor suregry, radiotherapy) and/or managed by observation.
4. Has any condition other than IPF that, in the opinion of the investigator, is likely to result in the death of the subject within the next 2 years.
5. Presence of other disease that may interfere with testing procedures or in the judgement of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial
6. Is likely to receive lung transplantation within the next 12 months.
7. Currently receiving high dose corticosteroid, cytotoxic (e.g., chlorambucil, azathioprine, cyclophosphamide, methotrexate), vasodilator therapy for pulmonary hypertension (e.g., bosentan), and or investigational therapy for IPF or administration of such therapeutics within 4 weeks of initial screening (or 5 half-lives, whichever is longer). Also see excluded concomitant medicines (section 7.3). A current dose of less than or equal to 15 mg/day of prednisone or its equivalent is acceptable if the dose is anticipated to remain stable during the study. Short term use (<1month) of higher dose corticosteroid treatment (e.g. to manage IPF exacerbations) is also permitted.
8. Has a history of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous six months, including, but not limited to, the following:
a. Unstable angina pectoris or myocardial infarction, or percutaneous coronary intervention within the last 6 months
b. Congestive heart failure requiring hospitalization
c. Uncontrolled clinically significant arrhythmias.
9. If female, the subject is pregnant or lactating or intending to become pregnant before participating in this study during the study and within (5 half- lives PLUS 30 days) after last dose of the study drug; or intending to donate ova during such time period.
10. Woman considered to be of childbearing potential who do not use highly effective birth control methods (A/B/C) during the study.
A. Highly effective methods of birth control (when used consistently and correctly) are:
o intrauterine device (IUD) placed at least 4 weeks prior to the IMP administration
o bilateral tubal occlusion
o vasectomised partnerB
o sexual abstinenceC.
o combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal.
o progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable.
o intrauterine hormone-releasing system (IUS).
B. Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the woman of childbearing potential trial subject and that thevasectomised partner has received medical assessment of the surgical success.
C. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial.