The purpose of this trial is to demonstrate proof of concept of clinical activity of BI 1015550 on the change of Forced Vital Capacity (FVC) between baseline and 12 weeks. New treatments are needed that further reduce the decline in FVC, positively…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the change from baseline in FVC at 12 weeks (in mL).
Secondary outcome
The secondary endpoint is the Percentage of patients (%) N with Treatment
Emergent Adverse Events (TEAE).
Background summary
IPF is a progressive, fibrosing interstitial lung disease (ILD) characterized
by decline in lung function and worsening dyspnea. IPF carries a poor
prognosis, with a median post-diagnosis survival in untreated patients of
approximately 3 years.
IPF occurs worldwide. The prevalence of the disease appears to be increasing,
although it is unclear whether this reflects increased recognition or a true
increase in incidence. The incidence of IPF appears to be higher in North
America and Europe (3 to 9 cases per 100,000 person-years) than in South
America and East Asia (fewer than 4 cases per 100,000 person-years). In the
United States, the prevalence of IPF has been reported to range from 10 to 60
cases per 100,000. Increasing rates of hospital admissions and deaths due to
IPF also suggest an increasing burden of disease.
Nintedanib and pirfenidone are the only drugs registered for the treatment of
IPF and recommended in the recent ATS/ERS/JRS/ALAT Clinical Practice Guideline
for the Treatment of Idiopathic Pulmonary Fibrosis. Despite the availability of
these drugs, the medical need remains high in this devastating disease.
Study objective
The purpose of this trial is to demonstrate proof of concept of clinical
activity of BI 1015550 on the change of Forced Vital Capacity (FVC) between
baseline and 12 weeks. New treatments are needed that further reduce the
decline in FVC, positively affect symptoms and improve quality of life in
patients with Idiopathic Pulmonary Fibrosis. This trial will investigate BI
1015550 to be used in this patient population either as stand-alone treatment
or in addition to local standard of care (SoC), which may or may not include
currently approved antifibrotic treatments (nintedanib or pirfenidone). FVC
change from baseline will be used to generate sufficient evidence of efficacy
in the subpopulation on no background antifibrotic treatment, to inform the
phase III program.
Study design
This phase II trial is a double-blind, placebo-controlled comparison of BI
1015550 18 mg b.i.d over 12 weeks in patients treated with antifibrotic
treatment or not treated with antifibrotic treatment at baseline.
See protocol section 3.1
Intervention
BI 1015550 18mg b.i.d. will be given for 12 weeks. Please see section 4 -
investigational treatments
Study burden and risks
Preclinical experiments have shown that BI 1015550 affects the fibrotic pathway
and the effects may be complementary and/or synergistic to those of nintedanib.
Based on this, it is postulated that BI 1015550 may provide therapeutic benefit
to patients with IPF or other progressive fibrosing ILDs but this has not yet
been determined clinically.
Due to the limited short treatment duration in this study, only patients on no
background antifibrotic treatment may have an improvement of FVC versus
baseline. Nevertheless, patients* participation in this 12 weeks trial in IPF
patients with or without background antifibrotic therapy treated with BI
1015550, 18 mg b.i.d. is of utmost importance to investigate the safety,
tolerability, efficacy and PK profile of BI 1015550 when administered alone or
on background antifibrotic treatment prior to progressing to longer term
treatment Phase III to show an effect on FVC decline in the overall IPF
population.
Two PDE4 inhibitors are marketed with indications of psoriasis and chronic
obstructive pulmonary disease (COPD). Studies conducted in non-human primates
with both marketed compounds suggest that primates are less sensitive than rats
to PDE4i-associated toxicity. No adverse vascular changes in humans have been
reported.
Overall, BI 1015550 is expected to be safe and well tolerated with an improved
tolerability compared to other marketed PDE4 inhibitors due to lower affinity
for PDE4 D.
Comeniusstraat 6
Alkmaar 1817MS
NL
Comeniusstraat 6
Alkmaar 1817MS
NL
Listed location countries
Age
Inclusion criteria
Patients aged *40 years when signing the informed consent.
Diagnosis:
a. IPF based on 2018 ATS/ERS/JRS/ALAT Guideline [R18-2794] as confirmed by the
investigator based on chest HRCT scan taken within 12 months of Visit 1 and if
available surgical lung biopsy.
b. UIP or probable UIP HRCT pattern consistent with the clinical diagnosis of
IPF
Stable for at least 8 weeks prior to Visit 1. Patients have to be either :
- not on therapy with nintedanib or pirfenidone for at least 8 weeks prior to
Visit 1 (combination of nintedanib plus pirfenidone not allowed), or
- on stable* therapy with nintedanib or pirfenidone for at least 8 weeks prior
to Visit 1 and planning to stay stable on this background therapy after
randomisation.
- Forced Vital Capacity (FVC) *45% of predicted normal at Visit 1
- DLCO (corrected for haemoglobin [Hb] [Visit 1]) > 25% to < 80% of predicted
normal at Visit 1.
- Signed and dated written informed consent in accordance with ICH-GCP and
local legislation prior to admission to the trial.
Exclusion criteria
- Relevant airways obstruction (pre-bronchodilator FEV1/FVC < 0.7) at Visit 1.
- In the opinion of the Investigator, other clinically significant pulmonary
abnormalities.
- Acute IPF exacerbation within 4 months prior to screening and/or during the
screening period (investigator-determined).
- Lower respiratory tract infection requiring antibiotics within 4 weeks prior
to Visit 1 and/or during the screening period.
- Major surgery (major according to the investigator*s assessment) performed
within 3 months prior to Visit 1 or planned during the course of the trial.
(Being on a transplant list is allowed).
- Any documented active or suspected malignancy or history of malignancy within
5 years prior to Visit 1, except appropriately treated basal cell carcinoma of
the skin, *under surveillance* prostate cancer or in situ carcinoma of uterine
cervix.
- Evidence of active infection (chronic or acute) based on clinical exam or
laboratory findings (see table 5.2.3 :1) at Visit 1 or at Visit 2.
- Any suicidal behaviour in the past 2 years (i.e. actual attempt, interrupted
attempt, aborted attempt, or preparatory acts or behavior).
- The patient has a confirmed infection with SARS-CoV-2 within the 4 weeks
prior to Visit 1
and/or during the screening period.
- Further criteria apply.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004167-45-NL |
| CCMO | NL73653.056.20 |