Idiopathic Pulmonary Fibrosis (IPF)
Conditions
Keywords
TD139, Idiopathic pulmonary fibrosis, Galectin-3 inhibitor, GB0139
Brief summary
This is a randomized, double-blind, placebo-controlled phase 2b trial in subjects with IPF (idiopathic pulmonary fibrosis) investigating the efficacy and safety of GB0139.
Detailed description
This study is designed to evaluate the efficacy and safety of GB0139, a galectin-3 inhibitor, administered by dry powder inhalation over 52 weeks. GB0139, given once per day, will be compared to placebo. GB0139 was previously known as TD139.
Interventions
DRUGGB0139
GB0139 is a galectin-3 inhibitor designed to modulate the fibrogenic response to tissue injury. It is administered as inhalation once a day.
DRUGPlacebo
Placebo is administered as inhalation once a day
Sponsors
Syneos Health
bioRASI, LLC
Galecto Biotech AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This study is a double-blind study. The blinding will be maintained throughout the study.
Intervention model description
All subjects eligible for the study will be randomised into one of the two treatment arms: A. GB0139 3 mg once a day B. Placebo once a day
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female subjects aged ≥ 40 years of age with a diagnosis of IPF established during the previous five years according to ATS/ERS/Fleischner criteria. 2. Lung function parameters as follows: 1. Forced Vital Capacity (FVC) \> 45% of the predicted value at screening 2. Diffusion lung capacity for carbon monoxide (DLCO) (corrected for Hb) of 30% to 79% of the predicted value at screening 3. Subjects who currently are not being treated with nintedanib or pirfenidone; or cannot tolerate nintedanib or pirfenidone 4. Subjects must sign and date a written, IRB/EC approved informed consent form and any required authorization prior to initiation of any study procedures.
Exclusion criteria
1. Currently has significant airways obstruction: Forced Expiratory Volume in 1 s (FEV1)/Forced Vital Capacity (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, chronic lymphocytic leukaemia (under observation) and prostate cancer requiring anti-androgens, localised treatment (minor surgery, 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 nintedanib, pirfenidone, high dose corticosteroid, cytotoxic (e.g., chlorambucil, azathioprine, cyclophosphamide, methotrexate), vasodilator therapy for pulmonary hypertension (e.g., bosentan). 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. 8. Prior use of GB0139 (also called TD139) or previously randomized in GALACTIC-1. 9. Prior use of nintedanib or pirfenidone within 7 days of initiation of screening. 10. Prior use of investigational drugs within 30 days (or 5 half-lives, whichever is longer) of initiation of screening. 11. Participating in another clinical trial, either interventional or observational. 12. 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: 1. Unstable angina pectoris or myocardial infarction, or percutaneous coronary intervention within the last 6 months 2. Congestive heart failure requiring hospitalization 3. Uncontrolled clinically significant arrhythmias 13. 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. 14. Woman considered to be of childbearing potential who do not use highly effective birth control methods during the study. 15. Hypersensitivity to the active substance (TD139/GB0139) or the excipient (lactose).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Rate of Decline in Forced Vital Capacity (FVC) | 52 weeks | Efficacy of GB0139 as measured by the annual rate of decline in FVC expressed in mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Respiratory Related Hospitalizations | 52 weeks | Number of Participants with Respiratory Related Hospitalizations from randomisation (including acute exacerbation of IPF). |
| Assessment of Respiratory Related Quality of Life Using the St. George's Respiratory Questionnaire (SGRQ) | 52 weeks | Change from baseline to WK52 in the SGRQ total score. The SGRQ is a 50-item questionnaire split into three domains: symptoms, activity and impact. Weighting of both individual domains and the total score produces a range from 0 to 100, with higher scores indicating a poorer health-related quality of life. |
Countries
Australia, Belgium, Canada, France, Georgia, Germany, Ireland, Israel, Italy, Poland, Russia, Spain, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A. GB0139 3 mg Once a Day Inhalation of GB0139
GB0139: GB0139 is a galectin-3 inhibitor designed to modulate the fibrogenic response to tissue injury. It is administered as inhalation once a day. | 102 |
| B. Placebo Once a Day Inhalation of Placebo
Placebo: Placebo is administered as inhalation once a day | 70 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Change in Protocol forbidding use of Nintedanib / Pirfenidone | 30 | 22 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 12 | 9 |
Baseline characteristics
| Characteristic | Total | A. GB0139 3 mg Once a Day | B. Placebo Once a Day |
|---|---|---|---|
| Age, Continuous | 72.176 years STANDARD_DEVIATION 7.48 | 72.5 years STANDARD_DEVIATION 7.59 | 71.7 years STANDARD_DEVIATION 7.36 |
| Age, Customized Age, Categorical <70 | 60 Participants | 34 Participants | 26 Participants |
| Age, Customized Age, Categorical >=70 | 112 Participants | 68 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 158 Participants | 95 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 7 Participants | 2 Participants |
| Forced Vital Capacity (FVC) in mL | 2944.5 mL STANDARD_DEVIATION 867.88 | 3003.1 mL STANDARD_DEVIATION 861.58 | 2859.1 mL STANDARD_DEVIATION 876.13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 167 Participants | 98 Participants | 69 Participants |
| Region of Enrollment Australia | 9 participants | 8 participants | 1 participants |
| Region of Enrollment Canada | 2 participants | 1 participants | 1 participants |
| Region of Enrollment France | 7 participants | 4 participants | 3 participants |
| Region of Enrollment Georgia | 9 participants | 8 participants | 1 participants |
| Region of Enrollment Germany | 6 participants | 2 participants | 4 participants |
| Region of Enrollment Ireland | 2 participants | 1 participants | 1 participants |
| Region of Enrollment Israel | 15 participants | 10 participants | 5 participants |
| Region of Enrollment Italy | 3 participants | 1 participants | 2 participants |
| Region of Enrollment Poland | 11 participants | 6 participants | 5 participants |
| Region of Enrollment Russia | 8 participants | 6 participants | 2 participants |
| Region of Enrollment Spain | 5 participants | 1 participants | 4 participants |
| Region of Enrollment Ukraine | 6 participants | 4 participants | 2 participants |
| Region of Enrollment United Kingdom | 42 participants | 27 participants | 15 participants |
| Region of Enrollment United States | 48 participants | 24 participants | 24 participants |
| Sex: Female, Male Female | 49 Participants | 27 Participants | 22 Participants |
| Sex: Female, Male Male | 123 Participants | 75 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 102 | 5 / 70 |
| other Total, other adverse events | 80 / 102 | 50 / 70 |
| serious Total, serious adverse events | 24 / 102 | 11 / 70 |
Outcome results
Primary
Annual Rate of Decline in Forced Vital Capacity (FVC)
Efficacy of GB0139 as measured by the annual rate of decline in FVC expressed in mL
Time frame: 52 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| A. GB0139 3 mg Once a Day | Annual Rate of Decline in Forced Vital Capacity (FVC) | -316.60 mL/Year |
| B. Placebo Once a Day | Annual Rate of Decline in Forced Vital Capacity (FVC) | -127.41 mL/Year |
Secondary
Assessment of Respiratory Related Quality of Life Using the St. George's Respiratory Questionnaire (SGRQ)
Change from baseline to WK52 in the SGRQ total score. The SGRQ is a 50-item questionnaire split into three domains: symptoms, activity and impact. Weighting of both individual domains and the total score produces a range from 0 to 100, with higher scores indicating a poorer health-related quality of life.
Time frame: 52 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A. GB0139 3 mg Once a Day | Assessment of Respiratory Related Quality of Life Using the St. George's Respiratory Questionnaire (SGRQ) | 4.201 score on a scale | Standard Deviation 20.0648 |
| B. Placebo Once a Day | Assessment of Respiratory Related Quality of Life Using the St. George's Respiratory Questionnaire (SGRQ) | -4.77 score on a scale | Standard Deviation 14.7286 |
Secondary
Number of Participants With Respiratory Related Hospitalizations
Number of Participants with Respiratory Related Hospitalizations from randomisation (including acute exacerbation of IPF).
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A. GB0139 3 mg Once a Day | Number of Participants With Respiratory Related Hospitalizations | 17 Participants |
| B. Placebo Once a Day | Number of Participants With Respiratory Related Hospitalizations | 5 Participants |