Idiopathic Pulmonary Fibrosis
Conditions
Keywords
Japan, Phase2, Safety, Tolerability, Idiopathic Pulmonary Fibrosis, IPF, CAT-354, Tralokinumab
Brief summary
The purpose of the study is to evaluate the safety and tolerability of multiple-doses of tralokinumab in Japanese patients with Idiopathic Pulmonary Fibrosis.
Detailed description
This is a phase II, multicenter, blinded within cohort, dose-escalation study to evaluate the safety and tolerability of two ascending doses of tralokinumab in Japanese patients aged ≥ 50 years with mild to moderate Idiopathic Pulmonary Fibrosis.
Interventions
BIOLOGICALtralokinumab cohort 1
Tralokinumab is a human recombinant monoclonal antibody (MAb) of the subclass that specifically binds human IL-13, blocking interactions with the IL-13 receptor
BIOLOGICALtralokinumab cohort 2
Tralokinumab is a human recombinant monoclonal antibody (MAb) of the subclass that specifically binds human IL-13, blocking interactions with the IL-13 receptor
OTHERPlacebo
Sponsors
MedImmune LLC
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent prior to any study specific procedures * Confirmed IPF diagnosis for ≤ 5 years prior to Visit 1 (screening). Confirmation of diagnosis of IPF * Mild to moderate IPF to include all of the following at Visit 1 1. FVC ≥ 50% and ≤ 90% predicted normal 2. Partial pressure of oxygen in arterial blood (PaO2) of ≥ 55 mmHg on room air, or oxygen saturation by pulse oximetry (SpO2) of ≥ 90% on room air at rest 3. Hemoglobin-corrected diffusion capacity for carbon monoxide (DLCO) ≥ 30% and ≤ 90% predicted normal
Exclusion criteria
* History of clinically significant environmental exposure (eg, domestic and occupational) to a known cause of pulmonary fibrosis * Diagnosis of connective tissue disease or drug toxicity as the likely cause of the interstitial disease * A suspected IPF exacerbation not fully resolved and treatment completed ≤ 14 days prior to Visit 1 * A suspected IPF exacerbation during the screening period * A FEV1/FVC ratio \< 0.70 at the time of Visit 1 (postbronchodilator) * The extent of emphysema on the HRCT is greater than the extent of fibrosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | From baseline to Week 48 (treatment-emergent only) | Adverse events and serious adverse events using the Safety Population. Other variables used for the safety assessments include electrocardiogram, vital signs, and routine laboratory assessments. These variables as well as their changes from baseline will be summarized descriptively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Tralokinumab Concentration Data | From baseline to Week 48 (Week 0 [post-dose, within +5 minutes after end of infusion], Week 4 [pre-dose], Week 12 [pre-dose]. Week 28, Week 40, Week 48) | Serum tralokinumab concentration data will be summarized by treatment group. |
| Immunogenecity | From baseline to Week 48 | The incidence rate of positive serum antibodies to tralokinumab will be reported. |
Countries
Japan
Participant flow
Recruitment details
A total of 37 patients were screened at 5 centres in Japan, and 20 patients were randomized and received at least 1 dose of tralokinumab low dose, high dose, or placebo. The first patient entered the study on 24 January 2014 and the last patient last visit was on 19 November 2015.
Pre-assignment details
20 patients were randomized and received at least 1 dose of tralokinumab low dose, high dose, or placebo (tralokinumab low dose group: n=8, tralokinumab high dose group: n=8, placebo group: n=4).
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Tralokinumab 400 mg Q4W intravenously dosed for 24 weeks | 8 |
| High Dose Tralokinumab 800 mg Q4W intravenously dosed for 24 weeks | 8 |
| Placebo Placebo Q4W intravenously dosed for 24 weeks | 4 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Low Dose | High Dose | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 67.0 Years STANDARD_DEVIATION 7.1 | 65.0 Years STANDARD_DEVIATION 9.4 | 68.3 Years STANDARD_DEVIATION 8.5 | 66.5 Years STANDARD_DEVIATION 8 |
| Gender Female | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Gender Male | 6 Participants | 6 Participants | 4 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 7 / 8 | 2 / 4 |
| serious Total, serious adverse events | 2 / 8 | 1 / 8 | 1 / 4 |
Outcome results
Primary
Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events
Adverse events and serious adverse events using the Safety Population. Other variables used for the safety assessments include electrocardiogram, vital signs, and routine laboratory assessments. These variables as well as their changes from baseline will be summarized descriptively.
Time frame: From baseline to Week 48 (treatment-emergent only)
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At lease one adverse events | 8 Patients |
| Low Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one IP related adverse event | 1 Patients |
| Low Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one adverse event of ≥ grade 3 severity | 1 Patients |
| Low Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | Death (grade 5 severity) | 0 Patients |
| Low Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one serious adverse event | 2 Patients |
| Low Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one serious and ≥ grade 3 severity event | 0 Patients |
| Low Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one IP related serious adverse event | 0 Patients |
| Low Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one event leading to IP discontinuation | 2 Patients |
| High Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one adverse event of ≥ grade 3 severity | 0 Patients |
| High Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one IP related serious adverse event | 0 Patients |
| High Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | Death (grade 5 severity) | 0 Patients |
| High Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one serious adverse event | 1 Patients |
| High Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one serious and ≥ grade 3 severity event | 0 Patients |
| High Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At lease one adverse events | 7 Patients |
| High Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one IP related adverse event | 2 Patients |
| High Dose | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one event leading to IP discontinuation | 0 Patients |
| Placebo | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one adverse event of ≥ grade 3 severity | 0 Patients |
| Placebo | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one IP related adverse event | 0 Patients |
| Placebo | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At lease one adverse events | 2 Patients |
| Placebo | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | Death (grade 5 severity) | 0 Patients |
| Placebo | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one IP related serious adverse event | 0 Patients |
| Placebo | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one serious and ≥ grade 3 severity event | 0 Patients |
| Placebo | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one serious adverse event | 1 Patients |
| Placebo | Safety and Tolerability Primarily Assessed by the Number of Patients With Adverse Events | At least one event leading to IP discontinuation | 0 Patients |
Secondary
Immunogenecity
The incidence rate of positive serum antibodies to tralokinumab will be reported.
Time frame: From baseline to Week 48
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose | Immunogenecity | Anti-drug antibody positive post-baseline | 0 Patients |
| Low Dose | Immunogenecity | Anti-drug antibody positive at baseline | 1 Patients |
| High Dose | Immunogenecity | Anti-drug antibody positive post-baseline | 0 Patients |
| High Dose | Immunogenecity | Anti-drug antibody positive at baseline | 0 Patients |
| Placebo | Immunogenecity | Anti-drug antibody positive at baseline | 0 Patients |
| Placebo | Immunogenecity | Anti-drug antibody positive post-baseline | 0 Patients |
Secondary
Serum Tralokinumab Concentration Data
Serum tralokinumab concentration data will be summarized by treatment group.
Time frame: From baseline to Week 48 (Week 0 [post-dose, within +5 minutes after end of infusion], Week 4 [pre-dose], Week 12 [pre-dose]. Week 28, Week 40, Week 48)
Population: PK population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose | Serum Tralokinumab Concentration Data | Week 0 (post-dose) | 149 Microgram per milliliter | Standard Deviation 64.8 |
| Low Dose | Serum Tralokinumab Concentration Data | Week 4 (pre-dose) | 33.9 Microgram per milliliter | Standard Deviation 9.03 |
| Low Dose | Serum Tralokinumab Concentration Data | Week 12 (pre-dose) | 55.1 Microgram per milliliter | Standard Deviation 16.1 |
| Low Dose | Serum Tralokinumab Concentration Data | Week 28 | 61.4 Microgram per milliliter | Standard Deviation 29.1 |
| Low Dose | Serum Tralokinumab Concentration Data | Week 40 | 2.55 Microgram per milliliter | Standard Deviation 2.7 |
| Low Dose | Serum Tralokinumab Concentration Data | Week 48 | 0.515 Microgram per milliliter | Standard Deviation 0.759 |
| High Dose | Serum Tralokinumab Concentration Data | Week 40 | 2.69 Microgram per milliliter | Standard Deviation 1.72 |
| High Dose | Serum Tralokinumab Concentration Data | Week 0 (post-dose) | 313 Microgram per milliliter | Standard Deviation 46.6 |
| High Dose | Serum Tralokinumab Concentration Data | Week 28 | 87.5 Microgram per milliliter | Standard Deviation 50.9 |
| High Dose | Serum Tralokinumab Concentration Data | Week 4 (pre-dose) | 76.1 Microgram per milliliter | Standard Deviation 32.3 |
| High Dose | Serum Tralokinumab Concentration Data | Week 48 | 0.374 Microgram per milliliter | Standard Deviation 0.27 |
| High Dose | Serum Tralokinumab Concentration Data | Week 12 (pre-dose) | 75.7 Microgram per milliliter | Standard Deviation 41.8 |