Trial Outcomes & Findings for Efficacy and Safety of AMG0001 in Subjects With Critical Limb Ischemia (NCT NCT02144610)
NCT ID: NCT02144610
Last Updated: 2019-08-13
Results Overview
A frequency table for Day 0 to 6 months, Day 0 to 12 months and Day 0 to 18 months intervals by treatment group; the Fisher's Exact test was used for treatment comparison.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
46 participants
Primary outcome timeframe
18 months
Results posted on
2019-08-13
Participant Flow
This study enrolled patients with critical limb ischemia from 69 sites across the United States, Canada, and Europe. The last patient completed in November 28, 2016.
Of the 98 subjects screened, 46 met the entry criteria and were randomized (1:1) into the study to receive AMG0001 or placebo as 4 sets of injections 2 weeks apart at Day 0, Month 3, Month 9, and Month 12.
Participant milestones
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
Randomized subjects will receive 4 sets of intramuscular (IM) injections of hepatocyte growth factor (HGF) plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb, for a total of 16 sets of IM injections.
Each set will be 8 IM injections; each IM injection contains 3 mL AMG0001.
HGF Plasmid (AMG0001): IM
|
Placebo
Randomized subjects will receive 4 sets of intramuscular (IM) injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb, for a total of 16 sets of IM injections.
Each set will be 8 IM injections; each IM injection contains 3 mL placebo.
Matching Placebo: IM
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
23
|
|
Overall Study
COMPLETED
|
0
|
1
|
|
Overall Study
NOT COMPLETED
|
23
|
22
|
Reasons for withdrawal
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
Randomized subjects will receive 4 sets of intramuscular (IM) injections of hepatocyte growth factor (HGF) plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb, for a total of 16 sets of IM injections.
Each set will be 8 IM injections; each IM injection contains 3 mL AMG0001.
HGF Plasmid (AMG0001): IM
|
Placebo
Randomized subjects will receive 4 sets of intramuscular (IM) injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb, for a total of 16 sets of IM injections.
Each set will be 8 IM injections; each IM injection contains 3 mL placebo.
Matching Placebo: IM
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
5
|
|
Overall Study
Death
|
2
|
2
|
|
Overall Study
Study Discontinuation by Sponsor
|
19
|
14
|
|
Overall Study
Other
|
0
|
1
|
Baseline Characteristics
Number analyzed in row differs from overall due to missing measurements.
Baseline characteristics by cohort
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=23 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=23 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=23 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=46 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=23 Participants
|
9 Participants
n=23 Participants
|
18 Participants
n=46 Participants
|
|
Age, Categorical
>=65 years
|
14 Participants
n=23 Participants
|
14 Participants
n=23 Participants
|
28 Participants
n=46 Participants
|
|
Age, Continuous
|
67.5 years
STANDARD_DEVIATION 12 • n=23 Participants
|
67 years
STANDARD_DEVIATION 9.79 • n=23 Participants
|
67.3 years
STANDARD_DEVIATION 10.83 • n=46 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=23 Participants
|
7 Participants
n=23 Participants
|
13 Participants
n=46 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=23 Participants
|
16 Participants
n=23 Participants
|
33 Participants
n=46 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=23 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=46 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=23 Participants
|
23 Participants
n=23 Participants
|
46 Participants
n=46 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=23 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=46 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=23 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=46 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=23 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=46 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=23 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=46 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=23 Participants
|
2 Participants
n=23 Participants
|
5 Participants
n=46 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=23 Participants
|
21 Participants
n=23 Participants
|
39 Participants
n=46 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=23 Participants
|
0 Participants
n=23 Participants
|
2 Participants
n=46 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=23 Participants
|
0 Participants
n=23 Participants
|
0 Participants
n=46 Participants
|
|
Region of Enrollment
Canada
|
1 participants
n=23 Participants
|
1 participants
n=23 Participants
|
2 participants
n=46 Participants
|
|
Region of Enrollment
Belgium
|
1 participants
n=23 Participants
|
1 participants
n=23 Participants
|
2 participants
n=46 Participants
|
|
Region of Enrollment
Hungary
|
8 participants
n=23 Participants
|
6 participants
n=23 Participants
|
14 participants
n=46 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=23 Participants
|
12 participants
n=23 Participants
|
24 participants
n=46 Participants
|
|
Region of Enrollment
Poland
|
0 participants
n=23 Participants
|
1 participants
n=23 Participants
|
1 participants
n=46 Participants
|
|
Region of Enrollment
France
|
1 participants
n=23 Participants
|
2 participants
n=23 Participants
|
3 participants
n=46 Participants
|
|
Past Tobacco Use
Yes
|
14 Participants
n=23 Participants
|
18 Participants
n=23 Participants
|
32 Participants
n=46 Participants
|
|
Past Tobacco Use
No
|
9 Participants
n=23 Participants
|
5 Participants
n=23 Participants
|
14 Participants
n=46 Participants
|
|
Current Tobacco Use
Yes
|
6 Participants
n=23 Participants
|
6 Participants
n=23 Participants
|
12 Participants
n=46 Participants
|
|
Current Tobacco Use
No
|
17 Participants
n=23 Participants
|
17 Participants
n=23 Participants
|
34 Participants
n=46 Participants
|
|
Alcohol Use
Yes
|
8 Participants
n=23 Participants
|
6 Participants
n=23 Participants
|
14 Participants
n=46 Participants
|
|
Alcohol Use
No
|
15 Participants
n=23 Participants
|
17 Participants
n=23 Participants
|
32 Participants
n=46 Participants
|
|
Ulcer Present
|
11 Participants
n=23 Participants
|
13 Participants
n=23 Participants
|
24 Participants
n=46 Participants
|
|
Ischemic Rest Pain (cm)
|
5.03 cm
STANDARD_DEVIATION 2.92 • n=23 Participants • Number analyzed in row differs from overall due to missing measurements.
|
6.04 cm
STANDARD_DEVIATION 2.82 • n=21 Participants • Number analyzed in row differs from overall due to missing measurements.
|
5.52 cm
STANDARD_DEVIATION 2.89 • n=44 Participants • Number analyzed in row differs from overall due to missing measurements.
|
|
Ankle-brachial index (ABI) at baseline
|
0.449 ratio
STANDARD_DEVIATION 0.1944 • n=20 Participants • Number analyzed in row differs from overall due to missing measurements.
|
0.360 ratio
STANDARD_DEVIATION 0.2239 • n=20 Participants • Number analyzed in row differs from overall due to missing measurements.
|
0.392 ratio
STANDARD_DEVIATION 0.218 • n=40 Participants • Number analyzed in row differs from overall due to missing measurements.
|
|
Toe-brachial index (TBI) at baseline
|
0.134 ratio
STANDARD_DEVIATION 0.1280 • n=21 Participants • Number analyzed in row differs from overall due to missing measurements.
|
0.167 ratio
STANDARD_DEVIATION 0.1660 • n=18 Participants • Number analyzed in row differs from overall due to missing measurements.
|
0.149 ratio
STANDARD_DEVIATION 0.146 • n=39 Participants • Number analyzed in row differs from overall due to missing measurements.
|
PRIMARY outcome
Timeframe: 18 monthsA frequency table for Day 0 to 6 months, Day 0 to 12 months and Day 0 to 18 months intervals by treatment group; the Fisher's Exact test was used for treatment comparison.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=23 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=23 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-6 Months (MI)
|
1 Participants
|
0 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-12 Months (MI)
|
2 Participants
|
0 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-18 Months (MI)
|
2 Participants
|
0 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-6 Months (Stroke)
|
0 Participants
|
1 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-12 Months (Stroke)
|
1 Participants
|
1 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-18 Months (Stroke)
|
1 Participants
|
1 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-6 Months (Major Amputation)
|
5 Participants
|
7 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-12 Months (Major Amputation)
|
6 Participants
|
7 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-18 Months (Major Amputation)
|
6 Participants
|
7 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-6 Months (Revascularization)
|
3 Participants
|
2 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-12 Months (Revascularization)
|
6 Participants
|
3 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-18 Months (Revascularization)
|
6 Participants
|
3 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-6 Months (All-cause Death)
|
0 Participants
|
1 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-12 Months (All-cause Death)
|
2 Participants
|
2 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-18 Months (All-cause Death)
|
3 Participants
|
2 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-6 Months (Major Amputation or Death)
|
5 Participants
|
8 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-12 Months (Major Amputation or Death)
|
7 Participants
|
9 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-18 Months (Major Amputation or Death)
|
8 Participants
|
9 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-6 Months (Major Amputation or Revascularization)
|
7 Participants
|
9 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-12 Month (Major Amputation or Revascularization)
|
11 Participants
|
10 Participants
|
|
Major Amputation or Revascularization (of the Index Leg), All-cause Death, and Incidence of Stroke and Myocardial Infarction (MI)
0-18 Month (Major Amputation or Revascularization)
|
11 Participants
|
10 Participants
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: The number analyzed in one or more rows differs from overall number analyzed due to early discontinuation.
The severity of rest pain (based on the average over previous 7 days) recorded using the 10 cm visual analog scale (VAS). VAS is a 10-cm line (with score ranges 0 to 10), oriented horizontally; the left end of the line (0 mark) indicates "no pain"; the right end indicates "pain as bad as it can be." 1. The subject is asked to mark a place on the line corresponding to the average pain intensity experienced in the last 7 days. 2. The distance along the scale is converted into a numeric reading by measuring the distance of the subjects mark in cm from the beginning of the scale (the 0 mark).
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=19 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=16 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Change in Ischemic Rest Pain (in the Index Leg) From Baseline Using a 10 cm Visual Analog Scale (VAS) Scale
Change from Baseline at Month 3
|
0.40 score on a scale
Standard Deviation 2.310
|
-0.79 score on a scale
Standard Deviation 2.889
|
|
Change in Ischemic Rest Pain (in the Index Leg) From Baseline Using a 10 cm Visual Analog Scale (VAS) Scale
Change from Baseline at Month 6
|
0.20 score on a scale
Standard Deviation 3.002
|
-1.65 score on a scale
Standard Deviation 2.704
|
|
Change in Ischemic Rest Pain (in the Index Leg) From Baseline Using a 10 cm Visual Analog Scale (VAS) Scale
Change from Baseline at Month 9
|
-0.15 score on a scale
Standard Deviation 2.281
|
-0.90 score on a scale
Standard Deviation 2.801
|
|
Change in Ischemic Rest Pain (in the Index Leg) From Baseline Using a 10 cm Visual Analog Scale (VAS) Scale
Change from Baseline at Month 12
|
-2.39 score on a scale
Standard Deviation 2.156
|
0.00 score on a scale
Standard Deviation 0.200
|
|
Change in Ischemic Rest Pain (in the Index Leg) From Baseline Using a 10 cm Visual Analog Scale (VAS) Scale
Change from Baseline at Month 15
|
-0.80 score on a scale
Standard Deviation 1.825
|
2.40 score on a scale
Standard Deviation 1.980
|
|
Change in Ischemic Rest Pain (in the Index Leg) From Baseline Using a 10 cm Visual Analog Scale (VAS) Scale
Change from Baseline at LOCF
|
-1.61 score on a scale
Standard Deviation 2.863
|
-0.20 score on a scale
Standard Deviation 3.087
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: The number of participants analyzed are those that have an ulcer on the index leg at the time of enrollment (n=11 in HGF plasmid group, n=13 in placebo group).
A table showing the number of subjects with complete healing of the target ulcer by treatment. Ulcer healing of the largest ulcer on the index limb was assessed clinically by the Principal Investigator by direct visual inspection at each study visit. If the largest ulcer on the index leg was considered completely healed, photographs of the healed ulcer area was captured. If an ulcer healed completely during the study period, the ulcer was re-evaluated 2 weeks later to confirm it has remained healed. Confirmation of complete ulcer healing was made by an outside physician unconnected with the study and nominated for this purpose.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=11 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=13 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Ulcer Improvement
Baseline and up to Month 6
|
2 Participants
|
1 Participants
|
|
Ulcer Improvement
Baseline and up to Month 12
|
3 Participants
|
1 Participants
|
|
Ulcer Improvement
Baseline and up to Month 18
|
3 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: 18 monthsA table showing the number of subjects with improvement in VAS (≥ 20 mm) by treatment.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=23 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=23 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
VAS Improvement
Baseline and up to Month 6
|
4 Participants
|
6 Participants
|
|
VAS Improvement
Baseline and up to Month 12
|
9 Participants
|
6 Participants
|
|
VAS Improvement
Baseline and up to Month 18
|
9 Participants
|
6 Participants
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: The number analyzed in one or more rows differs from overall number analyzed due to early discontinuation.
Summary statistics were provided for baseline and change from baseline for right/left brachial systolic pressure by visit and treatment (only subjects with non-missing baseline and visit values). A two-way analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline as a covariate were performed for each visit and LOCF.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=19 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=15 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 3 (right)
|
0.7 mmHg
Standard Deviation 27.27
|
2.4 mmHg
Standard Deviation 18.78
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 6 (right)
|
-2.4 mmHg
Standard Deviation 23.49
|
0.7 mmHg
Standard Deviation 33.58
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 9 (right)
|
2.3 mmHg
Standard Deviation 14.50
|
-7.2 mmHg
Standard Deviation 26.52
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 12 (right)
|
-5.8 mmHg
Standard Deviation 16.76
|
5.0 mmHg
Standard Deviation 15.60
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 15 (right)
|
5.7 mmHg
Standard Deviation 22.81
|
13.0 mmHg
Standard Deviation 6.08
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 18 (right)
|
—
|
23.0 mmHg
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at LOCF (right)
|
-2.3 mmHg
Standard Deviation 24.36
|
8.2 mmHg
Standard Deviation 23.94
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 3 (left)
|
7.9 mmHg
Standard Deviation 27.37
|
-5.7 mmHg
Standard Deviation 22.24
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 6 (left)
|
-1.1 mmHg
Standard Deviation 28.61
|
-15.8 mmHg
Standard Deviation 30.04
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 9 (left)
|
-0.8 mmHg
Standard Deviation 14.52
|
-25.8 mmHg
Standard Deviation 30.78
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 12 (left)
|
0.6 mmHg
Standard Deviation 14.00
|
10.0 mmHg
Standard Deviation 11.36
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 15 (left
|
4.7 mmHg
Standard Deviation 21.01
|
-18.5 mmHg
Standard Deviation 38.89
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at Month 18 (left)
|
—
|
-2.0 mmHg
|
|
Hemodynamic Measurements - Mean Change From Baseline in Brachial (Right/Left) Systolic Pressure
Change from Baseline at LOCF (left)
|
2.6 mmHg
Standard Deviation 26.68
|
-0.9 mmHg
Standard Deviation 19.20
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: The number analyzed in one or more rows differs from overall number analyzed due to early discontinuation.
Summary statistics were provided for baseline and change from baseline for ankle systolic pressure measured at dorsalis pedis and posterior tibial by visit and treatment (only subjects with non-missing baseline and visit values). A two-way analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline as a covariate were performed for each visit and LOCF.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=14 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=12 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline at Month 3 (Dorsalis Pedis)
|
4.2 mmHg
Standard Deviation 35.66
|
11.2 mmHg
Standard Deviation 30.15
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline at Month 6 (Dorsalis Pedis)
|
12.7 mmHg
Standard Deviation 19.96
|
9.9 mmHg
Standard Deviation 22.73
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline at Month 9 (Dorsalis Pedis)
|
3.4 mmHg
Standard Deviation 40.59
|
3.0 mmHg
Standard Deviation 57.86
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline at Month 12 (Dorsalis Pedis)
|
59.4 mmHg
Standard Deviation 47.00
|
12.0 mmHg
Standard Deviation 15.62
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline at Month 15 (Dorsalis Pedis)
|
18.5 mmHg
Standard Deviation 10.61
|
3.0 mmHg
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline at LOCF (Dorsalis Pedis)
|
32.9 mmHg
Standard Deviation 41.55
|
16.7 mmHg
Standard Deviation 34.25
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline at Month 3 (Posterior Tibial)
|
15.2 mmHg
Standard Deviation 35.02
|
16.1 mmHg
Standard Deviation 31.81
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline at Month 6 (Posterior Tibial)
|
28.4 mmHg
Standard Deviation 28.32
|
19.2 mmHg
Standard Deviation 37.04
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline at Month 9 (Posterior Tibial)
|
4.5 mmHg
Standard Deviation 24.64
|
-3.5 mmHg
Standard Deviation 15.50
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline atMonth 12 (Posterior Tibial)
|
45.0 mmHg
Standard Deviation 28.86
|
4.3 mmHg
Standard Deviation 5.86
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline atMonth 15 (Posterior Tibial)
|
40.5 mmHg
Standard Deviation 51.62
|
-10.0 mmHg
|
|
Hemodynamic Measurements - Mean Change From Baseline in Ankle (Dorsalis Pedis/Posterior Tibial) Systolic Pressure
Change from Baseline at LOCF (Posterior Tibial)
|
35.1 mmHg
Standard Deviation 33.97
|
13.2 mmHg
Standard Deviation 24.98
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: The number analyzed in one or more rows differs from overall number analyzed due to early discontinuation.
Summary statistics were provided for baseline and change from baseline for toe systolic pressure by visit and treatment (only subjects with non-missing baseline and visit values). A two-way analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline as a covariate were performed for each visit and LOCF.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=16 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=11 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Hemodynamic Measurements - Mean Change From Baseline in Toe Systolic Pressure
Change from Baseline at Month 3
|
4.4 mmHg
Standard Deviation 19.96
|
-9.9 mmHg
Standard Deviation 25.07
|
|
Hemodynamic Measurements - Mean Change From Baseline in Toe Systolic Pressure
Change from Baseline at Month 6
|
19.5 mmHg
Standard Deviation 18.44
|
-6.3 mmHg
Standard Deviation 33.76
|
|
Hemodynamic Measurements - Mean Change From Baseline in Toe Systolic Pressure
Change from Baseline at Month 9
|
20.7 mmHg
Standard Deviation 20.38
|
29.3 mmHg
Standard Deviation 28.79
|
|
Hemodynamic Measurements - Mean Change From Baseline in Toe Systolic Pressure
Change from Baseline at Month 12
|
34.8 mmHg
Standard Deviation 37.38
|
39.3 mmHg
Standard Deviation 19.63
|
|
Hemodynamic Measurements - Mean Change From Baseline in Toe Systolic Pressure
Change from Baseline at Month 15
|
16.0 mmHg
Standard Deviation 33.05
|
6.5 mmHg
Standard Deviation 9.19
|
|
Hemodynamic Measurements - Mean Change From Baseline in Toe Systolic Pressure
Change from Baseline at Month 18
|
—
|
14.0 mmHg
|
|
Hemodynamic Measurements - Mean Change From Baseline in Toe Systolic Pressure
Change from Baseline at LOCF
|
18.5 mmHg
Standard Deviation 32.51
|
-2.9 mmHg
Standard Deviation 30.04
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: The number analyzed in one or more rows differs from overall number analyzed due to early discontinuation.
Summary statistics were provided for baseline and change from baseline for calculated ABI by visit and treatment (only subjects with non-missing baseline and visit values). A two-way analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline as a covariate were performed for each visit and LOCF.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=16 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=15 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Hemodynamic Measurements - Mean Change From Baseline in ABI of Index Leg
Change from Baseline at Month 3
|
-0.009 ratio
Standard Deviation 0.2612
|
0.105 ratio
Standard Deviation 0.1661
|
|
Hemodynamic Measurements - Mean Change From Baseline in ABI of Index Leg
Change from Baseline at Month 6
|
0.097 ratio
Standard Deviation 0.0920
|
0.028 ratio
Standard Deviation 0.2257
|
|
Hemodynamic Measurements - Mean Change From Baseline in ABI of Index Leg
Change from Baseline at Month 9
|
0.098 ratio
Standard Deviation 0.1001
|
0.246 ratio
Standard Deviation 0.3272
|
|
Hemodynamic Measurements - Mean Change From Baseline in ABI of Index Leg
Change from Baseline at Month 12
|
0.303 ratio
Standard Deviation 0.3481
|
0.098 ratio
Standard Deviation 0.0964
|
|
Hemodynamic Measurements - Mean Change From Baseline in ABI of Index Leg
Change from Baseline at Month 15
|
-0.077 ratio
Standard Deviation 0.2101
|
0.090 ratio
Standard Deviation 0.1556
|
|
Hemodynamic Measurements - Mean Change From Baseline in ABI of Index Leg
Change from Baseline at LOCF
|
0.115 ratio
Standard Deviation 0.3662
|
0.111 ratio
Standard Deviation 0.1855
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: The number analyzed in one or more rows differs from overall number analyzed due to early discontinuation.
Summary statistics were provided for baseline and change from baseline for calculated TBI by visit and treatment (only subjects with non-missing baseline and visit values). A two-way analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline as a covariate were performed for each visit and LOCF.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=17 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=14 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Hemodynamic Measurements - Mean Change From Baseline in TBI of Index Leg
Change from Baseline at Month 3
|
0.024 ratio
Standard Deviation 0.1661
|
-0.078 ratio
Standard Deviation 0.1536
|
|
Hemodynamic Measurements - Mean Change From Baseline in TBI of Index Leg
Change from Baseline at Month 6
|
0.133 ratio
Standard Deviation 0.1398
|
-0.037 ratio
Standard Deviation 0.2175
|
|
Hemodynamic Measurements - Mean Change From Baseline in TBI of Index Leg
Change from Baseline at Month 9
|
0.134 ratio
Standard Deviation 0.1493
|
0.112 ratio
Standard Deviation 0.1747
|
|
Hemodynamic Measurements - Mean Change From Baseline in TBI of Index Leg
Change from Baseline at Month 12
|
0.303 ratio
Standard Deviation 0.2945
|
0.238 ratio
Standard Deviation 0.2045
|
|
Hemodynamic Measurements - Mean Change From Baseline in TBI of Index Leg
Change from Baseline at Month 15
|
0.110 ratio
Standard Deviation 0.2261
|
0.035 ratio
Standard Deviation 0.0495
|
|
Hemodynamic Measurements - Mean Change From Baseline in TBI of Index Leg
Change from Baseline at Month 18
|
—
|
0.070 ratio
|
|
Hemodynamic Measurements - Mean Change From Baseline in TBI of Index Leg
Change from Baseline at LOCF
|
0.168 ratio
Standard Deviation 0.2692
|
-0.044 ratio
Standard Deviation 0.1846
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: The number analyzed in one or more rows differs from overall number analyzed due to early discontinuation.
The VascuQol contains 5 domains (pain, symptom, activities, social, and emotional functioning); responses were scored from 0 (lowest QOL, death) to 7 (best QOL, maximum health). Responses were averaged for composite overall and domain-specific scores, giving equal weight to each question and domain. The composite overall is the average of domain-specific scores. Responses after revascularization or major amputation were included in the analysis. In the event of death, subjects were scored as 0. For the effect of treatment on individual domains, pain, symptoms, and activities were considered the most important of the 5 domains. Summary statistics were provided for baseline and change from baseline by visit and treatment for VascuQol, including subscore, for subjects who had a non-missing value at both baseline and the specific visit. A two-way ANCOVA with treatment and region as fixed factors and baseline as a covariate were performed for each visit and LOCF.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=19 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=19 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Changes in the Quality of Life Using the Vascular Quality of Life Questionnaire (VascuQol) Over 18 Months
Pain (LOCF)
|
1.46 score on a scale
Standard Deviation 1.158
|
0.83 score on a scale
Standard Deviation 1.557
|
|
Changes in the Quality of Life Using the Vascular Quality of Life Questionnaire (VascuQol) Over 18 Months
Symptom (LOCF)
|
0.79 score on a scale
Standard Deviation 1.475
|
0.71 score on a scale
Standard Deviation 1.468
|
|
Changes in the Quality of Life Using the Vascular Quality of Life Questionnaire (VascuQol) Over 18 Months
Activities (LOCF)
|
0.59 score on a scale
Standard Deviation 0.950
|
0.66 score on a scale
Standard Deviation 0.981
|
|
Changes in the Quality of Life Using the Vascular Quality of Life Questionnaire (VascuQol) Over 18 Months
Social (LOCF)
|
0.53 score on a scale
Standard Deviation 1.086
|
0.39 score on a scale
Standard Deviation 1.852
|
|
Changes in the Quality of Life Using the Vascular Quality of Life Questionnaire (VascuQol) Over 18 Months
Emotional Functioning (LOCF)
|
0.77 score on a scale
Standard Deviation 1.247
|
0.83 score on a scale
Standard Deviation 1.458
|
|
Changes in the Quality of Life Using the Vascular Quality of Life Questionnaire (VascuQol) Over 18 Months
Composite Overall (LOCF)
|
0.81 score on a scale
Standard Deviation 0.843
|
0.74 score on a scale
Standard Deviation 1.068
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: The number analyzed in one or more rows differs from overall number analyzed due to early discontinuation.
The EQ-5D-5L descriptive system covers 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5); death was coded as a worst case. The EQ-5D-5L health state for each subject, referred to as a 5 digit code that combines 1 level from each of the 5 dimensions, was converted into a single index value using a published weighing system. The index value ranges from -0.109 to 1, where 1 indicates no problems in all 5 dimensions, and is reduced when a patient reports increasing problems. Summary statistics were provided for baseline and change from baseline by visit and treatment for EQ-5D-5L, including subscore, for subjects who had a non-missing value at both baseline and the specific visit. A two-way ANCOVA with treatment and region as fixed factors and baseline as a covariate were performed for each visit and LOCF.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=20 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=19 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Changes in the Quality of Life From Baseline Using the EQ-5D-5L Over 18 Months
Change from Baseline at Month 3
|
0.03 score on a scale
Standard Deviation 0.130
|
0.03 score on a scale
Standard Deviation 0.149
|
|
Changes in the Quality of Life From Baseline Using the EQ-5D-5L Over 18 Months
Change from Baseline at Month 6
|
0.01 score on a scale
Standard Deviation 0.127
|
0.04 score on a scale
Standard Deviation 0.114
|
|
Changes in the Quality of Life From Baseline Using the EQ-5D-5L Over 18 Months
Change from Baseline at Month 9
|
-0.06 score on a scale
Standard Deviation 0.168
|
0.07 score on a scale
Standard Deviation 0.092
|
|
Changes in the Quality of Life From Baseline Using the EQ-5D-5L Over 18 Months
Change from Baseline at Month 12
|
0.08 score on a scale
Standard Deviation 0.193
|
0.08 score on a scale
Standard Deviation 0.097
|
|
Changes in the Quality of Life From Baseline Using the EQ-5D-5L Over 18 Months
Change from Baseline at Month 15
|
-0.03 score on a scale
Standard Deviation 0.043
|
0.05 score on a scale
Standard Deviation 0.156
|
|
Changes in the Quality of Life From Baseline Using the EQ-5D-5L Over 18 Months
Change from Baseline at Month 18
|
—
|
-0.02 score on a scale
|
|
Changes in the Quality of Life From Baseline Using the EQ-5D-5L Over 18 Months
Change from Baseline at LOCF
|
0.04 score on a scale
Standard Deviation 0.194
|
0.03 score on a scale
Standard Deviation 0.153
|
POST_HOC outcome
Timeframe: Month 36Population: Subjects who had a major amputation or died during the study
The median time to major amputation or death was analyzed over the duration of the study as a post-hoc analysis; all reports of major amputation or death were included in this post hoc analysis, irrespective of pre-defined study windows.
Outcome measures
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=8 Participants
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=10 Participants
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Time to Major Amputation (of the Index Leg) or All-cause Death
|
505 Days
Interval 0.0 to 528.0
|
381 Days
Interval 0.0 to 539.0
|
Adverse Events
Gene Therapy HGF Plasmid (AMG0001)
Serious events: 7 serious events
Other events: 5 other events
Deaths: 3 deaths
Placebo
Serious events: 9 serious events
Other events: 7 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=23 participants at risk
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=23 participants at risk
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
|
|---|---|---|
|
Psychiatric disorders
suicidal ideation
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Infections and infestations
pneumonia
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Respiratory, thoracic and mediastinal disorders
respiratory failure
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Cardiac disorders
angina unstable
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Cardiac disorders
acute myocardial infarction
|
8.7%
2/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
General disorders
multiple organ dysfunction syndrome
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Nervous system disorders
cerebrovascular accident
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Vascular disorders
hypotension
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Cardiac disorders
cardiac failure congestive
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
non-small cell lung cancer
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Blood and lymphatic system disorders
anaemia
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Musculoskeletal and connective tissue disorders
intervertebral disc protrusion
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Cardiac disorders
cardiac arrest
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Respiratory, thoracic and mediastinal disorders
bronchitis chronic
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Infections and infestations
device related infection
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Injury, poisoning and procedural complications
vascular graft occlusion
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Injury, poisoning and procedural complications
fall
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Injury, poisoning and procedural complications
laceration
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Infections and infestations
sepsis
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Injury, poisoning and procedural complications
hip fracture
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Nervous system disorders
carotid artery occlusion
|
0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
Other adverse events
| Measure |
Gene Therapy HGF Plasmid (AMG0001)
n=23 participants at risk
Randomized subjects will receive 4 sets of intramuscular injections of HGF plasmid two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
HGF Plasmid (AMG0001): IM
|
Placebo
n=23 participants at risk
Randomized subjects will receive 4 sets of intramuscular injections of matching placebo two weeks apart starting at Day 0 and again at Month 3 (first cycle) and at Month 9 and again at Month 12 (second cycle) in muscles of the affected lower limb.
Matching Placebo: IM
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|---|---|---|
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Infections and infestations
urinary tract infection
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13.0%
3/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Infections and infestations
nasopharyngitis
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8.7%
2/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
4.3%
1/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
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Gastrointestinal disorders
nausea
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0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
13.0%
3/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
|
Gastrointestinal disorders
constipation
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0.00%
0/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
|
8.7%
2/23 • Adverse events (AEs) were documented from the start of the first dose of study product (Day 0) to the end of the follow-up period (Month 18).
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place