Peripheral Artery Disease
Conditions
Keywords
Peripheral artery disease, Intermittent claudication, magnetic resonance imaging
Brief summary
This study was designed to assess the safety, tolerability and efficacy of ACZ885 on the leg artery structure and physical activity in patients with atherosclerotic peripheral artery disease and leg pain from walking.
Interventions
Dosage form: solution for injection Strength: 150 mg/1 mL Mode of administration: subcutaneous use.
DRUGPlacebo
Matching placebo of Canakinumab
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Must have a signed informed consent form. * Must be between the ages of 18 and 85 * Must experience leg pain associated with walking and have an ankle brachial index between 0.40 and 0.9 * Must be on stable aspirin and statin doses for at least 6 weeks * Blood pressure within ranges specified in the protocol * Able to communicate well with the Investigator and understand and comply with the study procedures Key
Exclusion criteria
* Recent use of any other experimental drugs * Pregnant or nursing women * Women of child bearing potential unless willing to use contraception as detailed in the protocol * Cannot walk 15 meters (50 feet) * People on restricted medications as listed in the protocol * Any open or non-healing wounds with 3 months of study start or infection within 2 weeks or study start * Significant heart disease * Uncontrolled diabetes * Significant kidney or liver disease * Live vaccinations within 3 months of study start * History of untreated tuberculosis or active tuberculosis (TB) * Patients with metal in their body (excluded due to MRI scan) as detailed in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Vessel Wall Area Ratio of 12 Months to Baseline | Baseline, 12 months post-dose | Peripheral artery wall area (superficial femoral artery) measured using Magnetic Resonance Imaging (MRI) cross-section slices. Mean vessel wall area (mm\^2) was derived by converting total plaque volume (TPV) (mL) of the vessel to mm\^3 by multiplying by 1000, dividing by the number of slices used for the volume calculation, and dividing by the thickness of a slice (3 mm). Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, the treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events in 12 Months | Baseline to 12 months post-dose | Summary statistics on adverse event is reported. It is categorized as number of patients in total adverse events (non serious and serious AEs), serious adverse event, death. |
| Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline | Baseline, 12 months post-dose | Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects. |
| High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline | Baseline, 12 months post-dose | Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects. |
Countries
Germany, Jordan, United States
Participant flow
Pre-assignment details
A total of 38 patients were enrolled into the study.
Participants by arm
| Arm | Count |
|---|---|
| Canakinumab (ACZ885) Monthly subcutaneous doses of Canakinumab 150 mg/1 mL for 12 months | 18 |
| Placebo Monthly subcutaneous doses of placebo of Canakinumab 150 mg/1 mL for 12 months | 20 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 5 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Protocol deviation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Canakinumab (ACZ885) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 66.0 years STANDARD_DEVIATION 8.64 | 63.5 years STANDARD_DEVIATION 7.98 | 64.7 years STANDARD_DEVIATION 8.29 |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 18 | 17 / 20 |
| serious Total, serious adverse events | 10 / 18 | 10 / 20 |
Outcome results
Primary
Mean Vessel Wall Area Ratio of 12 Months to Baseline
Peripheral artery wall area (superficial femoral artery) measured using Magnetic Resonance Imaging (MRI) cross-section slices. Mean vessel wall area (mm\^2) was derived by converting total plaque volume (TPV) (mL) of the vessel to mm\^3 by multiplying by 1000, dividing by the number of slices used for the volume calculation, and dividing by the thickness of a slice (3 mm). Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, the treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.
Time frame: Baseline, 12 months post-dose
Population: The pharmacodynamics (PD) analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients who underwent iliac/femoral stenting were removed from all data points that occurred after this procedure in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab (ACZ885) | Mean Vessel Wall Area Ratio of 12 Months to Baseline | 1.05 Ratio | Standard Error 0.03 |
| Placebo | Mean Vessel Wall Area Ratio of 12 Months to Baseline | 0.99 Ratio | Standard Error 0.04 |
p-value: 0.28490% CI: [0.97, 1.15]Mixed Models Analysis
Secondary
High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline
Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.
Time frame: Baseline, 12 months post-dose
Population: The PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients with baseline and 12 month data are included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab (ACZ885) | High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline | 0.62 Ratio | Standard Error 0.14 |
| Placebo | High Sensitivity C-reactive Protein (hsCRP) Ratio of 12 Months to Baseline | 0.83 Ratio | Standard Error 0.2 |
Secondary
Number of Patients With Adverse Events in 12 Months
Summary statistics on adverse event is reported. It is categorized as number of patients in total adverse events (non serious and serious AEs), serious adverse event, death.
Time frame: Baseline to 12 months post-dose
Population: All patients that received any study drug were included in the safety analysis set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Canakinumab (ACZ885) | Number of Patients With Adverse Events in 12 Months | Death | 1 Participants |
| Canakinumab (ACZ885) | Number of Patients With Adverse Events in 12 Months | Total Adverse events | 16 Participants |
| Canakinumab (ACZ885) | Number of Patients With Adverse Events in 12 Months | Serious Adverse events | 10 Participants |
| Placebo | Number of Patients With Adverse Events in 12 Months | Total Adverse events | 20 Participants |
| Placebo | Number of Patients With Adverse Events in 12 Months | Serious Adverse events | 10 Participants |
| Placebo | Number of Patients With Adverse Events in 12 Months | Death | 0 Participants |
Secondary
Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline
Least squares mean for ratio of 12 months to baseline was measured from repeated measures mixed effect model with visit, treatment, treatment-by-visit interaction, baseline and the visit-by-baseline interaction as fixed effects.
Time frame: Baseline, 12 months post-dose
Population: The PD analysis set included all patients with available PD data and no protocol deviations with relevant impact on PD data. Patients with baseline and 12 month data are included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Canakinumab (ACZ885) | Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline | 0.62 Ratio | Standard Error 0.12 |
| Placebo | Serum Amyloid A (SAA) Level Ratio of 12 Months to Baseline | 0.79 Ratio | Standard Error 0.17 |