A Study Measuring the Effectiveness, Safety, and Tolerability of BMS-986278 in Participants With Lung Fibrosis
- Registration Number
- NCT04308681
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to provide an initial evaluation of the effectiveness of BMS-986278 in participants with lung fibrosis, to demonstrate the safety of BMS-986278, and provide information on the drug levels of BMS-986278 in these participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 403
For the idiopathic pulmonary fibrosis (IPF) Cohort
- Diagnosis of IPF within 7 years of screening
- Female and males ≥ 40 years of age
For the progressive fibrotic interstitial lung disease (PF-ILD) Cohort
- Evidence of progressive ILD within the 24 months before screening
- Female and male ≥ 21 years of age.
- Women of childbearing potential (WOCBP)
- Active Smokers
- Current malignancy or previous malignancy up to 5 years prior to screening
- History of allergy to BMS-986278 or related compounds
Other protocol-defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IPF Dose 1 + Post Treatment Follow-up or OTE BMS-986278 IPF (Idiopathic Pulmonary Fibrosis) OTE (Optional Treatment Extension) IPF Placebo + Post Treatment Follow-up or OTE BMS-986278 Placebo - PF-ILD Dose 1 + Post Treatment Follow-up or OTE BMS-986278 PF-ILD (Progressive Fibrotic Interstitial Lung Disease) PF-ILD Dose 2 + Post Treatment Follow-up or OTE BMS-986278 - PF-ILD Placebo + Post Treatment Follow-up or OTE BMS-986278 Placebo - IPF Dose 2 + Post Treatment Follow-up or OTE BMS-986278 -
- Primary Outcome Measures
Name Time Method Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) in IPF Participants From baseline (first dose) up to week 26 Percent predicted forced vital capacity (ppFVC) is the percentage of predicted value per participant of forced vital capacity (FVC). FVC is defined as the maximum capacity of air that a participant can exhale after a maximum inspiration as measured by the volume of air exhaled in a spirometer. The data is reported as percent change from baseline in ppFVC. Percent change from baseline is a calculation that expresses the change in a value compared to its initial starting point (baseline) as a percentage, showing how much a value has increased or decreased relative to its original level; it's calculated by subtracting the baseline value from the new value, dividing by the baseline value, and then multiplying by 100%. The percent change in this endpoint was calculated from ppFVC values taken at baseline, which is defined as the measurement of ppFVC taken at first dose, and ppFVC values taken at Week 26. This endpoint reports data for the IPF cohort only as pre-specified in the protocol.
- Secondary Outcome Measures
Name Time Method The Number of Participants Experiencing Adverse Events (AEs) From first dose up to 30 days after last dose during the main study treatment phase An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.
The Number of Participants Experiencing Serious Adverse Events (SAEs) From first dose up to 30 days after last dose during the main study treatment phase A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.
The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation From first dose up to 30 days after last dose during the main study treatment phase The number of participants who discontinued study treatment due to adverse events (AEs)
The Number of Participants Who Died Due to Adverse Events (AEs) From first dose up to 30 days after last dose during the main study treatment phase The number of participants who died while receiving study treatment due to an adverse event
Maximum Concentration (Cmax) On Day 1 and Week 4 (Day 29) Cmax is defined as the maximum concentration of the analyte recorded in the participants. Cmax of BMS-986278 and BMT-327319 was derived from plasma concentration versus time data.
Time to Maximum Concentration (Tmax) On Day 1 and Week 4 (Day 29) Tmax is defined as the amount of time until the maximum concentration of the analyte is recorded in the participants
Area Under Curve (AUC0-8) On Day 1 and Week 4 (Day 29) Area under the plasma concentration-time curve (AUC) from the timepoint of 0 hours to 24 hours post dose as measured on Day 1 and Week 4.
Concentration Trough (Ctrough) On Week 4 (Day 29) and Week 12 (Day 85) Ctrough is defined as the lowerst concentration of drug in the blood immediately before the next dose is administered
The Number of Participants Experiencing Electrocardiogram (ECG) Abnormalities At Week 26 A frequency summary of investigator clinical interpretation of ECG abnormal findings is listed.
Change From Baseline in Vital Sign Measurements At baseline and Week 26 The change from baseline in select vital sign measurements. Baseline is defined as first dose.
Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) in PF-ILD Participants At baseline and Week 26 Percent predicted forced vital capacity (ppFVC) is the percentage of predicted value per participant of forced vital capacity (FVC). FVC is defined as the maximum capacity of air that a participant can exhale after a maximum inspiration as measured by the volume of air exhaled in a spirometer. The data is reported as percent change from baseline in ppFVC. Percent change from baseline is a calculation that expresses the change in a value compared to its initial starting point (baseline) as a percentage, showing how much a value has increased or decreased relative to its original level; it's calculated by subtracting the baseline value from the new value, dividing by the baseline value, and then multiplying by 100%. The percent change in this endpoint was calculated from ppFVC values taken at baseline, which is defined as the measurement of ppFVC taken at first dose, and ppFVC values taken at Week 26. This endpoint reports data for PF-ILD cohort only as pre-specified in the protocol.
The Number of Participants With ≥ 10% Absolute Decline in ppFVC (%) At Weeks 4, 8, 12, 16, 20, and 26 The number of participants with ≥ 10% absolute decline in percent predicted forced vital capacity (ppFVC) at pre-specified timepoints.
ppFVC is the maximum capacity of air that a participant can exhale after a maximum inspiration. It measures the volume of air exhaled in a spirometer, after a maximal inspiration. It is reported as the percentage of the predicted value for the participant.
The number of participants represented signify the number of participants with applicable data during the specific visit at the specific timepoint.The Number of Participants With 0% Change in ppFVC (%) Weeks 4, 8, 12, 16, 20, and 26 The number of participants with 0% change in percent predicted forced vital capacity (ppFVC) at pre-specified timepoints.
ppFVC is the maximum capacity of air that a participant can exhale after a maximum inspiration. It measures the volume of air exhaled in a spirometer, after a maximal inspiration. It is reported as the percentage of the predicted value for the participant.Time to First Occurrence ≥ 10% Absolute Decline in ppFVC (%) From first dose up to the first occurrence of ≥ 10% absolute decline in ppFVC The amount of time in weeks to the participant's first occurrence ≥ 10% absolute decline in Percent Predicted Forced Vital Capacity (ppFVC). A participant's time is censored at the last observed time prior to discontinuation if a participant discontinues study without event, or at week 26 if a participant does not experience the event until the end of week 26. Kaplan-Meier product limit method will be employed to estimate the survival curves.
ppFVC is the maximum capacity of air that a participant can exhale after a maximum inspiration. It measures the volume of air exhaled in a spirometer, after a maximal inspiration. It is reported as the percentage of the predicted value for the participant.Absolute Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) From baseline up to Weeks 4, 8, 12, 16, 20, and 26 The absolute change in ppFVC (%) is measured from baseline up to the pre-specified timepoints of Weeks 4, 8, 12, 16, 20, and 26.
ppFVC is the maximum capacity of air that a participant can exhale after a maximum inspiration. It measures the volume of air (mL) exhaled in a spirometer, after a maximal inspiration. It is reported as the percentage of the predicted value for the participant.Absolute Change From Baseline in Forced Vital Capacity (FVC) From baseline up to Weeks 4, 8, 12, 16, 20, and 26 Forced vital capacity (FVC) is defined as the amount of air that can be forcibly exhaled from your lungs after taking the deepest breath possible. The absolute change in FVC (mL) is measured from baseline up to Weeks 4, 8, 12, 16, 20, and 26.
Absolute Change From Baseline in Single Breath Diffusing Capacity of Carbon Monoxide (DLCO SB) From baseline up to Week 26 The absolute change in single breath diffusing capacity of carbon monoxide (DLCO SB) (mL/min/mmHg) (corrected for hemoglobin) from baseline to Week 26. DLCO is defined as a measurement of the extent to which oxygen passes from the alveoli into the blood. Baseline is defined as first dose.
Absolute Change From Baseline in Percent Predicted Single Breath Diffusing Capacity of Carbon Monoxide (ppDLCO SB) From baseline up to Week 26 The absolute change in percent predicted single breath diffusing capacity of carbon monoxide (DLCO SB) (mL/min/mmHg) (corrected for hemoglobin) from baseline to Week 26. DLCO is defined as a measurement of the extent to which oxygen passes from the alveoli into the blood. Baseline is defined as first dose.
Absolute Change From Baseline in Walking Endurance/Distance From baseline up to Week 26 The absolute change in walking endurance/distance as determined by the 6-minute walk test (6MWT) from baseline to Week 26. The 6-Minute Walk Test (6MWT) is a submaximal exercise test used to assess aerobic capacity and endurance. Baseline is defined as first dose.
Time to First Acute Exacerbation From the first dose up to the day of the first acute exacerbation or Week 26, whichever comes first Time to first acute exacerbations of lung fibrosis was measured from the day of first dose up to the day of first acute exacerbation. Participants who discontinued the study treatment prior to the end of the main study without experiencing the event were excluded from the analysis. A participant's time was censored at the last observed time prior to discontinuation if a participant discontinued study without event, or at week 26 if a participant did not experience the event until the end of week 26.
Acute exacerbations were defined as an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality, as follows:
1. Acute worsening or development of dyspnea (\< 1 month duration)
2. Imaging with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia
3. Respiratory deterioration not fully explained by cardiac failure or fluid overloadThe Number of Participants Experiencing Acute Exacerbation From the first dose up to the day of the first acute exacerbation or Week 26, whichever comes first The number of participants experiencing acute exacerbations of lung fibrosis.
Acute exacerbations were defined as an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality, as follows:
1. Acute worsening or development of dyspnea (\< 1 month duration)
2. Imaging with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia
3. Respiratory deterioration not fully explained by cardiac failure or fluid overload
Trial Locations
- Locations (105)
Local Institution - 0174
🇨🇳Taipei, Taiwan
Local Institution - 0175
🇨🇳Taipei, Taiwan
Local Institution - 0050
🇬🇧Cambridge, United Kingdom
Local Institution - 0163
🇬🇧Edinburgh, United Kingdom
Local Institution - 0041
🇬🇧London, United Kingdom
Local Institution - 0092
🇬🇧London, United Kingdom
Local Institution - 0140
🇪🇸L'Hospitalet de Llobregat, Spain
Local Institution - 0137
🇪🇸Madrid, Spain
Local Institution - 0039
🇪🇸Pozuelo de Alarcon, Spain
Local Institution - 0147
🇪🇸Santander, Spain
Local Institution - 0176
🇨🇳Kaohsiung, Taiwan
Local Institution - 0032
🇺🇸Birmingham, Alabama, United States
Local Institution
🇬🇧London, United Kingdom
Local Institution - 0028
🇺🇸Los Angeles, California, United States
Local Institution - 0043
🇺🇸Stanford, California, United States
University of Colorado Anschutz Medical Campus-Department of Medicine
🇺🇸Aurora, Colorado, United States
Local Institution - 0006
🇺🇸Denver, Colorado, United States
Local Institution - 0171
🇺🇸New Haven, Connecticut, United States
Local Institution - 0035
🇺🇸Gainesville, Florida, United States
Local Institution - 0166
🇺🇸Orlando, Florida, United States
Local Institution - 0078
🇺🇸Atlanta, Georgia, United States
Local Institution - 0031
🇺🇸Kansas City, Kansas, United States
Local Institution - 0154
🇺🇸Baltimore, Maryland, United States
Local Institution - 0003
🇺🇸Boston, Massachusetts, United States
Local Institution - 0030
🇺🇸Chesterfield, Missouri, United States
Local Institution - 0036
🇺🇸Saint Louis, Missouri, United States
Local Institution - 0029
🇺🇸Cincinnati, Ohio, United States
Local Institution - 0164
🇺🇸Columbus, Ohio, United States
Local Institution - 0096
🇺🇸Charlottesville, Virginia, United States
Local Institution - 0049
🇦🇷Buenos Aires, Distrito Federal, Argentina
Local Institution - 0103
🇦🇷Rosario, Santa FE, Argentina
Local Institution - 0097
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
Local Institution - 0115
🇦🇷Buenos AIres, Argentina
Local Institution - 0048
🇦🇷Buenos Aires, Argentina
Local Institution - 0122
🇦🇷Mendoza, Argentina
Local Institution - 0045
🇦🇺Camperdown, New South Wales, Australia
Local Institution - 0025
🇦🇺Westmead, New South Wales, Australia
Local Institution - 0026
🇦🇺Brisbane, Queensland, Australia
Local Institution - 0046
🇦🇺Greenslopes, Queensland, Australia
Local Institution - 0022
🇦🇺Adelaide, South Australia, Australia
Local Institution - 0023
🇦🇺Heidelberg, Victoria, Australia
Local Institution - 0021
🇦🇺Murdoch, Western Australia, Australia
Local Institution - 0044
🇦🇺Nedlands, Western Australia, Australia
Local Institution - 0074
🇧🇪Brussels, Belgium
Local Institution - 0065
🇧🇪Leuven, Belgium
Local Institution - 0051
🇧🇪Liège, Belgium
Local Institution - 0076
🇧🇷Sao Paulo, Brazil
Local Institution - 0141
🇨🇦Vancouver, British Columbia, Canada
Local Institution - 0134
🇨🇦Toronto, Ontario, Canada
Local Institution - 0094
🇨🇦Montréal, Quebec, Canada
Local Institution - 0144
🇨🇦Sherbrooke, Quebec, Canada
Local Institution - 0127
🇨🇦Quebec, Canada
Local Institution - 0108
🇨🇱Curicó, Maule, Chile
Local Institution - 0054
🇨🇱Talca, Maule, Chile
Local Institution - 0038
🇨🇱Quillota, Valparaiso, Chile
Local Institution - 0187
🇨🇳Beijing, Beijing, China
Local Institution - 0183
🇨🇳Beijing, Beijing, China
Local Institution - 0188
🇨🇳Wuhan, Hubei, China
Local Institution - 0189
🇨🇳Shanghai, Shanghai, China
Local Institution - 0120
🇫🇷Bobigny, France
Local Institution - 0066
🇫🇷Bron, France
Local Institution - 0136
🇫🇷Dijon, France
Local Institution - 0162
🇫🇷Marseille, France
Hopital Europeen Georges Pompidou
🇫🇷Paris, France
Local Institution - 0143
🇫🇷Paris, France
Local Institution - 0067
🇫🇷Rennes, France
Local Institution - 0132
🇫🇷Toulouse, France
Local Institution - 0111
🇩🇪Hannover, Niedersachsen, Germany
Local Institution - 0107
🇩🇪Essen, Germany
Local Institution - 0093
🇩🇪Grosshansdorf, Germany
Local Institution - 0110
🇩🇪Heidelberg, Germany
Local Institution - 0121
🇩🇪Munich, Germany
Local Institution - 0119
🇩🇪Stuttgart, Germany
Local Institution - 0145
🇮🇱Tel Aviv, Tel-Aviv, Israel
Local Institution - 0113
🇮🇱Haifa, Israel
Local Institution - 0149
🇮🇱Jerusalem, Israel
Local Institution - 0114
🇮🇱Petah Tikva, Israel
Local Institution - 0148
🇮🇱Ramat Gan, Israel
Local Institution - 0073
🇮🇹Catania, Italy
Local Institution - 0077
🇮🇹Modena, Italy
Local Institution - 0089
🇮🇹Monza, Italy
Local Institution - 0072
🇮🇹Roma, Italy
Local Institution - 0155
🇯🇵Seto, Aichi, Japan
Local Institution - 0106
🇯🇵Koriyama, Fukushima, Japan
Local Institution - 0180
🇯🇵Sapporo, Hokkaido, Japan
Local Institution - 0095
🇯🇵Kobe, Hyogo, Japan
Local Institution - 0169
🇯🇵Kobe, Hyogo, Japan
Local Institution - 0071
🇯🇵Yokohama, Kanagawa, Japan
Local Institution - 0112
🇯🇵Sakai, Osaka, Japan
Local Institution - 0128
🇯🇵Izumo, Shimane, Japan
Local Institution - 0064
🇯🇵Hamamatasu, Shizuoka, Japan
Local Institution - 0080
🇯🇵Bunkyo-ku, Tokyo, Japan
Local Institution - 0153
🇯🇵Minato-ku, Tokyo, Japan
Local Institution - 0177
🇯🇵Shinjyuku-ku, Tokyo, Japan
Local Institution - 0117
🇯🇵Kumamoto, Japan
Local Institution - 0146
🇯🇵Nagasaki, Japan
Local Institution - 0170
🇯🇵Saitama, Japan
Local Institution - 0173
🇯🇵Tokyo, Japan
Local Institution - 0087
🇰🇷Seoul, Korea, Republic of
Local Institution - 0086
🇰🇷Seoul, Korea, Republic of
Local Institution - 0109
🇲🇽Monterrey, N.l., Nuevo Leon, Mexico
Local Institution - 0081
🇲🇽Monterrey, Nuevo LEON, Mexico
Local Institution - 0083
🇲🇽San Nicolas de los Garza, Nuevo LEON, Mexico
Local Institution - 0156
🇲🇽Oaxaca de Juarez, Oaxaca, Mexico
Local Institution - 0116
🇪🇸Barcelona, Spain