Management of Progressive Disease in Idiopathic Pulmonary Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 21 August 2023
• Main ID: NCT03939520
• Date of registration: 03/05/2019
• Prospective Registration: Yes
• Primary sponsor: Hospices Civils de Lyon
• Public title: Management of Progressive Disease in Idiopathic Pulmonary Fibrosis PROGRESSION
• Scientific title: Pragmatic Management of Progressive Disease in Idiopathic Pulmonary Fibrosis: a Randomized Trial
• Date of first enrolment: June 11, 2020
• Target sample size: 378
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03939520
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

France

Contacts

• Name: Vincent COTTIN, Pr
• Affiliation: Hospices Civils de Lyon

• Name: Vincent COTTIN, Pr

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patient aged = 50 years.

- Patient with Idiopathic Pulmonary Fibrosis satisfying the ATS/ERS/JRS/ALAT diagnostic
criteria (29) diagnosed.

In the absence of a surgical lung biopsy, high-resolution computed tomography (HRCT) must
be "consistent with Usual Interstitial Pneumonia (UIP)" defined as meeting either criteria
A, B, and C, or criteria A and C, or criteria B and C below:

A. Definite honeycomb lung destruction with basal and peripheral predominance. B. Presence
of reticular abnormality and traction bronchiectasis consistent with fibrosis, with basal
and peripheral predominance.

C. Atypical features are absent, specifically nodules and consolidation. Ground glass
opacity, if present, is less extensive than reticular opacity pattern.

- - Patient who fulfill at least 1 of the 4 criteria for IPF progression in the 12
months (+/- one six months) before screening, despite antifibrotic treatment in
clinical practice (if yes check the option(s)). These criteria are: 0 Relative decline
in FVC =10% predicted 0 Relative decline in FVC =5-<10% predicted and worsened
respiratory symptoms 0 Relative decline in FVC =5-<10% predicted and increased extent
of fibrotic changes on chest imaging 0 Worsened respiratory symptoms and increased
extent of fibrotic changes on chest imaging

- Patient must have been on a stable dose of pirfenidone or nintedanib prescribed as
first-line therapy for at least 6 months, with good tolerance of 1602 to 2403 mg per
day of pirfenidone or 200 to 300 mg per day of nintedanib.

- Patient who has a FVC = 45% of predicted.

- Patient who has a forced expiratory volume in 1 second (FEV1)/FVC ratio > 0.70.

- Patient who has a life expectancy of at least 9 months.

- Patient who has provided his written informed consent to participate in the study.

- Patient affiliated to a social insurance regimen.

Exclusion Criteria:

- Patients under judicial protection.

- Female patient who is pregnant or lactating, or is of child bearing potential (defined
as a sexually mature woman not surgically sterilized or not post-menopausal for at
least 24 consecutive months if = 55 years or 12 months if > 55 years) and who did not
agree to use highly effective methods of birth control throughout the study.

- Patient who is currently on both pirfenidone and nintedanib.

- Patient who has already received pirfenidone and nintedanib either concomitantly or
successively.

- Patient who has a contra-indication to pirfenidone or nintedanib.

- Patient who has emphysema > 15% on HRCT or the extent of emphysema is greater than the
extent of fibrosis according to reported results from the most recent HRCT.

- Patient who had acute exacerbation of idiopathic pulmonary fibrosis within the
previous 3 months.

- Patient who has a history of cigarette smoking within the previous 3 months.

- Patient who has received experimental therapy for IPF within 4 weeks before baseline.

- Patient who is receiving systemic corticosteroids equivalent to prednisone > 15 mg/day
or equivalent within 2 weeks before baseline.

- Patient who received Immuno-suppressants (e.g. methotrexate, azathioprine,
cyclophosphamide, cyclosporine, sirolimus, everolimus or other immunosuppressants)
within 4 weeks before baseline.

- Patient who has a history of a malignancy within the previous 5 years, with the
exception of basal cell skin neoplasms. In addition, a malignant diagnosis or
condition first occurring prior to 5 years must be considered cured, inactive, and not
under current treatment.

- Patient who, in the Investigator's opinion, is not able to perform home spirometry in
accordance with the protocol.

- Patient who has any concurrent condition other than IPF that, in the Investigator's
opinion, is unstable and/or would impact the likelihood of survival for the study
duration or the subject's ability to complete the study as designed, or may influence
any of the safety or efficacy assessments included in the study.

- Patient who has baseline resting oxygen saturation of < 88% on room air or
supplemental oxygen.

- Patient who had lung transplantation or who is on a lung transplant list and the
investigator anticipates the patient will not be able to complete the study prior to
transplant.



Age minimum: 50 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Progressive Idiopathic Pulmonary Fibrosis

Intervention(s)

Drug: pirfenidone and nintedanib

Drug: pirfenidone or nintedanib

Primary Outcome(s)

Slope of the decline in the forced vital capacity (FVC) measured by spirometry [Time Frame: 24 weeks]

Secondary Outcome(s)

Quality of live assessed by the "Analogy and Likert" scale for the evaluation of dyspnea, cough and respiratory health [Time Frame: 24 weeks]

Time from randomization to acute exacerbation of idiopathic pulmonary fibrosis [Time Frame: 24 weeks]

Time from randomization to initiation of supplementary oxygen therapy [Time Frame: 24 weeks]

Progression of disease on imaging by computed tomography [Time Frame: 24 weeks]

The proportion of patients who continue intent-to-treat therapy [Time Frame: 24 weeks]

Link between CA-125 variations and disease progression, the endpoint will be the slope of the FVC (exploratory) [Time Frame: 24 weeks]

Hospitalization-free survival [Time Frame: 24 weeks]

Quality of live assessed by the "Pulmonary Fibrosis (L-PF)" questionnaire [Time Frame: 24 weeks]

Time to permanent study drug discontinuation [Time Frame: 24 weeks]

Link between biomarkers variations and disease progression, the endpoint will be the slope of the FVC (exploratory) [Time Frame: 24 weeks]

Time to treatment failure [Time Frame: 24 weeks]

Proportion of decrease = 10% FVC relative decline or death [Time Frame: 24 weeks]

Quality of live assessed by EuroQoL 5-dimension 5-level Questionnaire [Time Frame: 24 weeks]

Time from randomization to death [Time Frame: 24 weeks]

Time from randomization to the first non-elective hospitalization from pulmonary cause [Time Frame: 24 weeks]

Quality of live assessed by King's Brief Interstitial Lung Disease Questionnaire [Time Frame: 24 weeks]

Secondary ID(s)

69HCL19_0029

2019-004326-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors