Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
This study will evaulate the long-term safety, efficacy and pharmacokinetics (PK) of recombinant human pentraxin-2 (rhPTX-2; PRM-151) zinpentraxin alfa, administered by intravenous (IV) infusion to participants with idiopathic pulmonary fibrosis (IPF).
Detailed description
This study is being conducted for the treatment of eligible participants who have taken part in Study PRM-151-202 and received the open-label study drug or completed the Phase III Study WA42293 with PRM-151. Participants who have discontinued treatment from or have completed Study WA42293 and do not want to receive PRM-151 in this study, will be invited to enroll in survival follow-up.
Interventions
Cohort A: Participants will receive three loading doses of open-label PRM-151 on days 1, 3, and 5, then one infusion every 4 weeks (Q4W). 10 mg/kg of PRM 151 will be administered by intravenous (IV) infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks. Cohort B: Participants previously randomized to the placebo in WA42293 will receive study medication in the three loading doses on days 1, 3 and 5 in a blinded fashion. All three doses will contain PRM-151. Participants previously randomized to the treatment arm in WA42293 will receive study medication in the three loading doses on days 1, 3 and 5 in a blinded fashion. One of the three doses will contain PRM-151, whereas two doses will contain placebo.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Taken part in either of the prior PRM-151 studies: PRM-151-202 or WA42293. * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception. * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.
Exclusion criteria
* Acute respiratory or systemic bacterial, viral, or fungal infection at the first visit of the OLE, or within 2 weeks of the first visit for patients joining Cohort A (from Study PRM-151-202). * History of smoking within 3 months prior to the first visit in the OLE. * History of alcohol or substance use disorder within 2 years prior to the first visit of the OLE or known or suspected active alcohol or substance-use disorder. * History of severe allergic reaction or anaphylactic reaction to PRM-151. * Clinically significant abnormality on ECG during eligibility assessment that, in the opinion of the investigator, may pose an additional risk in administering study drug to the participant. * Prolonged corrected QT interval \> 450 ms (for men) or \> 470 ms (for women) based on the Fridericia correction formula. * Clinically significant laboratory test abnormalities (hematology, serumchemistry, and urinalysis) that, in the opinion of the investigator, may pose an additional risk in administering study drug to the participant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) | From baseline until 8 weeks after the final dose, an average of 6 months | An AE was defined as any untoward medical occurrence in a clinical investigation participant who was administered a pharmaceutical product, regardless of causal attribution. Grading was completed according to the CTCAE, version 5.0. |
| Percentage of Participants With Infusion Related Reactions (IRRs) and Other AEs of Special Interest | From baseline until 8 weeks after the final dose, an average of 6 months | IRRs were defined as AEs that occurred during or within 24 hours after study drug administration and were judged to be related to study drug infusion. |
| Percentage of of Participants Permanently Discontinuing Study Treatment Due to AEs | From baseline until 8 weeks after the final dose, an average of 6 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Carbon Monoxide Diffusing Capacity (DLCO) | At Baseline, Week 24 and Week 48 | — |
| Time to Disease Progression | From baseline until study completion (up to approximately 1.5 years) | Time to first occurrence of \>=10% absolute decline in % predicted FVC, \>=15% relative decline in 6MWD, or death |
| Survival | Every 6 Months and at study completion (up to approximately 1.5 years) | — |
| IPF-related Mortality | Every 6 Months and at study completion (up to approximately 1.5 years) | — |
| Annual Rate of Change in Forced Vital Capacity (FVC) (mL) | From baseline until study completion (up to approximately 1.5 years) | — |
| Plasma Concentrations of PRM-151 at Specified Timepoints | Days 1 and 5, Weeks 4, and 12 | Due to early termination of the study, only participants enrolled in Cohort A receiving at least one IV dose of zinpentraxin alfa had their plasma concentrations analyzed. |
| Prevalence of Anti-drug Antibodies (ADAs) to PRM-151 at Baseline | Baseline (Day 1) | Due to early termination of the study, only ADA samples from participants in Cohort A were analyzed. |
| Percentage of Participants With ADAs During the Study | Weeks 4, 12 and 24 | Due to early termination of the study, only ADA samples from participants in Cohort A were analyzed. |
| Respiratory-related Mortality | Every 6 Months and at study completion (up to approximately 1.5 years) | — |
| Annual Rate of Change in 6-Minute Walk Distance (6MWD) | From baseline until study completion (up to approximately 1.5 years) | — |
| Annual Rate of Change in FVC% Predicted | From baseline until study completion (up to approximately 1.5 years) | — |
Countries
Argentina, Australia, Belgium, Canada, China, Czechia, Denmark, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Singapore, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United States
Participant flow
Recruitment details
Participants were enrolled across 48 investigative sites in 16 countries.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Zinpentraxin Alfa Participants entered this Cohort following participation in study PRM-151-202. | 21 |
| Cohort B: Ex-Placebo Participants entered, following participation in study WA42293. | 49 |
| Cohort B: Zinpentraxin Alfa Participants entered, following participation in study WA42293. | 47 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Death | 0 | 2 | 2 |
| Overall Study | Grade 4 infusion related reaction (IRR) | 1 | 0 | 0 |
| Overall Study | Lung Transplant | 0 | 0 | 1 |
| Overall Study | Study Terminated By Sponsor | 19 | 47 | 41 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Cohort A: Zinpentraxin Alfa | Cohort B: Ex-Placebo | Cohort B: Zinpentraxin Alfa | Total |
|---|---|---|---|---|
| Age, Continuous | 74.5 Years STANDARD_DEVIATION 5.5 | 74.6 Years STANDARD_DEVIATION 7.6 | 73.2 Years STANDARD_DEVIATION 6.8 | 74.0 Years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 47 Participants | 45 Participants | 110 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 19 Participants | 47 Participants | 43 Participants | 109 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 10 Participants | 25 Participants |
| Sex: Female, Male Male | 16 Participants | 39 Participants | 37 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 2 / 49 | 2 / 47 |
| other Total, other adverse events | 14 / 21 | 16 / 49 | 14 / 47 |
| serious Total, serious adverse events | 5 / 21 | 8 / 49 | 6 / 47 |
Outcome results
Primary
Percentage of of Participants Permanently Discontinuing Study Treatment Due to AEs
Time frame: From baseline until 8 weeks after the final dose, an average of 6 months
Population: The safety-evaluable population included all enrolled participants who received at least one administration (full or partial dose) of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Percentage of of Participants Permanently Discontinuing Study Treatment Due to AEs | 2 Participants |
| Cohort B: Ex-Placebo | Percentage of of Participants Permanently Discontinuing Study Treatment Due to AEs | 2 Participants |
| Cohort B: Zinpentraxin Alfa | Percentage of of Participants Permanently Discontinuing Study Treatment Due to AEs | 1 Participants |
Primary
Percentage of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a clinical investigation participant who was administered a pharmaceutical product, regardless of causal attribution. Grading was completed according to the CTCAE, version 5.0.
Time frame: From baseline until 8 weeks after the final dose, an average of 6 months
Population: The safety-evaluable population included all enrolled participants who received at least one administration (full or partial dose) of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Percentage of Participants With Adverse Events (AEs) | 18 Participants |
| Cohort B: Ex-Placebo | Percentage of Participants With Adverse Events (AEs) | 25 Participants |
| Cohort B: Zinpentraxin Alfa | Percentage of Participants With Adverse Events (AEs) | 26 Participants |
Primary
Percentage of Participants With Infusion Related Reactions (IRRs) and Other AEs of Special Interest
IRRs were defined as AEs that occurred during or within 24 hours after study drug administration and were judged to be related to study drug infusion.
Time frame: From baseline until 8 weeks after the final dose, an average of 6 months
Population: The safety-evaluable population included all enrolled participants who received at least one administration (full or partial dose) of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Percentage of Participants With Infusion Related Reactions (IRRs) and Other AEs of Special Interest | 2 Participants |
| Cohort B: Ex-Placebo | Percentage of Participants With Infusion Related Reactions (IRRs) and Other AEs of Special Interest | 2 Participants |
| Cohort B: Zinpentraxin Alfa | Percentage of Participants With Infusion Related Reactions (IRRs) and Other AEs of Special Interest | 4 Participants |
Secondary
Annual Rate of Change in 6-Minute Walk Distance (6MWD)
Time frame: From baseline until study completion (up to approximately 1.5 years)
Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Annual Rate of Change in 6-Minute Walk Distance (6MWD) | -86.95 Meters (m) |
| Cohort B: Ex-Placebo | Annual Rate of Change in 6-Minute Walk Distance (6MWD) | 64.64 Meters (m) |
| Cohort B: Zinpentraxin Alfa | Annual Rate of Change in 6-Minute Walk Distance (6MWD) | -163.66 Meters (m) |
Secondary
Annual Rate of Change in Forced Vital Capacity (FVC) (mL)
Time frame: From baseline until study completion (up to approximately 1.5 years)
Population: The full analysis set included all enrolled participants who received at least one administration (full or partial dose) of study drug.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Annual Rate of Change in Forced Vital Capacity (FVC) (mL) | -229.12 Milliliter (mL) |
| Cohort B: Ex-Placebo | Annual Rate of Change in Forced Vital Capacity (FVC) (mL) | -272.96 Milliliter (mL) |
| Cohort B: Zinpentraxin Alfa | Annual Rate of Change in Forced Vital Capacity (FVC) (mL) | -120.77 Milliliter (mL) |
Secondary
Annual Rate of Change in FVC% Predicted
Time frame: From baseline until study completion (up to approximately 1.5 years)
Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Annual Rate of Change in FVC% Predicted | -6.96 Percent predicted |
| Cohort B: Ex-Placebo | Annual Rate of Change in FVC% Predicted | -6.91 Percent predicted |
| Cohort B: Zinpentraxin Alfa | Annual Rate of Change in FVC% Predicted | -3.37 Percent predicted |
Secondary
Change in Carbon Monoxide Diffusing Capacity (DLCO)
Time frame: At Baseline, Week 24 and Week 48
Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization. In the Ex-placebo arm, no participant was assessed for DLCO after baseline. Due to short length of follow-up, no DLCO assessment was collected at Week 48 for Cohort B: Zinpentraxin Alfa arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Zinpentraxin Alfa | Change in Carbon Monoxide Diffusing Capacity (DLCO) | Baseline | 40.20 DLCO% Predicted | Standard Deviation 16.29 |
| Cohort A: Zinpentraxin Alfa | Change in Carbon Monoxide Diffusing Capacity (DLCO) | Week 24 | 1.08 DLCO% Predicted | Standard Deviation 4.05 |
| Cohort A: Zinpentraxin Alfa | Change in Carbon Monoxide Diffusing Capacity (DLCO) | Week 48 | -2.80 DLCO% Predicted | Standard Deviation 3.76 |
| Cohort B: Ex-Placebo | Change in Carbon Monoxide Diffusing Capacity (DLCO) | Baseline | 44.91 DLCO% Predicted | Standard Deviation 10.94 |
| Cohort B: Zinpentraxin Alfa | Change in Carbon Monoxide Diffusing Capacity (DLCO) | Baseline | 42.27 DLCO% Predicted | Standard Deviation 11.14 |
| Cohort B: Zinpentraxin Alfa | Change in Carbon Monoxide Diffusing Capacity (DLCO) | Week 24 | -1.55 DLCO% Predicted | — |
Secondary
IPF-related Mortality
Time frame: Every 6 Months and at study completion (up to approximately 1.5 years)
Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | IPF-related Mortality | NA Months |
| Cohort B: Ex-Placebo | IPF-related Mortality | NA Months |
| Cohort B: Zinpentraxin Alfa | IPF-related Mortality | NA Months |
Secondary
Percentage of Participants With ADAs During the Study
Due to early termination of the study, only ADA samples from participants in Cohort A were analyzed.
Time frame: Weeks 4, 12 and 24
Population: The immunogenicity population included all randomized participants with at least one postdose ADA assessment and were grouped according to treatment received or, if no treatment is received prior to study discontinuation, according to treatment assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Percentage of Participants With ADAs During the Study | 0 Percentage of Participants |
Secondary
Plasma Concentrations of PRM-151 at Specified Timepoints
Due to early termination of the study, only participants enrolled in Cohort A receiving at least one IV dose of zinpentraxin alfa had their plasma concentrations analyzed.
Time frame: Days 1 and 5, Weeks 4, and 12
Population: The pharmacokinetic population included all randomized participants who received at least one administration (full or partial dose) of zinpentraxin alfa and at least one evaluable postdose PK sample that was above the lower limit of quantification (LLOQ).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort A: Zinpentraxin Alfa | Plasma Concentrations of PRM-151 at Specified Timepoints | Week 12 - 2h Post Infusion | 215.65 micrograms per millilitre (ug/mL) | Standard Deviation 50.47 |
| Cohort A: Zinpentraxin Alfa | Plasma Concentrations of PRM-151 at Specified Timepoints | Day 1 - 2h Post Infusion | 203.85 micrograms per millilitre (ug/mL) | Standard Deviation 55.72 |
| Cohort A: Zinpentraxin Alfa | Plasma Concentrations of PRM-151 at Specified Timepoints | Day 5 - Pre Infusion | 42.83 micrograms per millilitre (ug/mL) | Standard Deviation 18.89 |
| Cohort A: Zinpentraxin Alfa | Plasma Concentrations of PRM-151 at Specified Timepoints | Day 5 - 2h Post Infusion | 252.90 micrograms per millilitre (ug/mL) | Standard Deviation 53.42 |
| Cohort A: Zinpentraxin Alfa | Plasma Concentrations of PRM-151 at Specified Timepoints | Week 4 - Pre Infusion | 2.50 micrograms per millilitre (ug/mL) | Standard Deviation 0 |
| Cohort A: Zinpentraxin Alfa | Plasma Concentrations of PRM-151 at Specified Timepoints | Week 4 - 2h Post Infusion | 209.00 micrograms per millilitre (ug/mL) | Standard Deviation 42.93 |
| Cohort A: Zinpentraxin Alfa | Plasma Concentrations of PRM-151 at Specified Timepoints | Week 12 - Pre Infusion | 2.50 micrograms per millilitre (ug/mL) | Standard Deviation 0 |
| Unknown | Plasma Concentrations of PRM-151 at Specified Timepoints | Day 1 -pre infusion | — micrograms per millilitre (ug/mL) | — |
Secondary
Prevalence of Anti-drug Antibodies (ADAs) to PRM-151 at Baseline
Due to early termination of the study, only ADA samples from participants in Cohort A were analyzed.
Time frame: Baseline (Day 1)
Population: The immunogenicity population included all randomized participants with at least one postdose ADA assessment and were grouped according to treatment received or, if no treatment is received prior to study discontinuation, according to treatment assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Prevalence of Anti-drug Antibodies (ADAs) to PRM-151 at Baseline | 0 Participants |
Secondary
Respiratory-related Mortality
Time frame: Every 6 Months and at study completion (up to approximately 1.5 years)
Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Respiratory-related Mortality | NA Months |
| Cohort B: Ex-Placebo | Respiratory-related Mortality | NA Months |
| Cohort B: Zinpentraxin Alfa | Respiratory-related Mortality | NA Months |
Secondary
Survival
Time frame: Every 6 Months and at study completion (up to approximately 1.5 years)
Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Survival | NA Months |
| Cohort B: Ex-Placebo | Survival | NA Months |
| Cohort B: Zinpentraxin Alfa | Survival | NA Months |
Secondary
Time to Disease Progression
Time to first occurrence of \>=10% absolute decline in % predicted FVC, \>=15% relative decline in 6MWD, or death
Time frame: From baseline until study completion (up to approximately 1.5 years)
Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Zinpentraxin Alfa | Time to Disease Progression | 5.6 Months |
| Cohort B: Ex-Placebo | Time to Disease Progression | NA Months |
| Cohort B: Zinpentraxin Alfa | Time to Disease Progression | NA Months |