Effect of SNF472 on Progression of Cardiovascular Calcification in End-Stage-Renal-Disease (ESRD) Patients on Hemodialysis (HD)
Study Details
Study Description
Brief Summary
The primary objective is to assess the effect of 2 dose levels of SNF472 (300 mg and 600 mg) compared to placebo on the progression of coronary artery calcium volume score over a 12-month (52 weeks) period in ESRD patients on HD
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Reducing the progression of cardiovascular calcification (CVC) in HD patients may improve the severe burden of CV disease related to the underlying ESRD. As no therapy is currently indicated to target CVC, there is a need to investigate the ability of SNF472 to reduce CVC progression and, ultimately, to improve CV outcomes in HD patients. This phase 2b double-blind, randomised, placebo-controlled study is designed to assess the effect of SNF472 on the progression of CVC as measured by calcium volume and CAC/Agatston scores in ESRD patients receiving HD. The study hypothesis is that administration of SNF472 over 52 weeks can slow the progression of CVC in this patient population compared to placebo.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SNF472 300 mg Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) |
Drug: SNF472
Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions.
|
| Experimental: SNF 472 600 mg Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) |
Drug: SNF472
Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions.
|
| Placebo Comparator: Matching Placebo Placebo arm: 2 vials of physiological saline |
Drug: Placebo
Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions.
|
Outcome Measures
Primary Outcome Measures
- Change in Log CAC Volume Score From Baseline to Week 52 for the Combined Dose Groups vs Placebo [Baseline (Week 1, Day 1) and Week 52]
Coronary Artery Calcification (CAC) Volume Score is a calculation to quantify the calcification of coronary artery calcium without factoring in the calcium density as measured by the CAC Agatston Score. The CAC Score was log-transformed and the primary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for the combined dose groups vs placebo. The primary analysis used an ANCOVA model with the change in log volume score (log 52-week volume score - log baseline volume score) as the dependent variable and with a fixed effect term for the combined randomized treatment groups and log CAC volume score at baseline as a covariate. The least squares means for the treatment groups was estimated and back transformed. A smaller change from baseline to follow up is a better outcome.
Secondary Outcome Measures
- Change in Log CAC Volume Score From Baseline to Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo [Baseline (Week 1, Day 1) and Week 52]
Coronary Artery Calcification (CAC) Volume Score is a calculation to quantify the calcification of coronary artery calcium without factoring in the calcium density as measured by the CAC Agatston Score. The CAC Score was log-transformed and the primary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for the combined dose groups vs placebo. This secondary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for each dose group vs placebo. The analysis used an ANCOVA model with the change in log volume score (log 52-week volume score - log baseline volume score) as the dependent variable and with a fixed effect term for each randomized treatment groups and log CAC volume score at baseline as a covariate. The least squares means for each of the treatment groups was estimated and back transformed. A smaller change from baseline to follow up is a better outcome.
- Change in Log CAC Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and for the Combined Dose Groups vs the Placebo Group [Baseline (Week 1, Day 1) and Week 52]
Coronary Artery Calcification (CAC) Agatston Score is a semi-automated tool to calculate a score the reflects the extent of coronary artery calcification as detected by an unenhanced CT scan. Scores range from 0 to >1000 Agatston units where higher scores indicate an increased amount of calcification and an increased risk for a major adverse cardiac event. This secondary outcome measure was the change in Log CAC Agatston Score from Baseline to Week 52 for each dose group and the treated arms combined vs placebo. The analysis used an ANCOVA model with the change in log score (log 52-week score - log baseline score) as the dependent variable and with a fixed effect term for each randomized treatment groups and log CAC score at baseline as a covariate. The least squares means for each of the treatment groups separately and combined was estimated and back transformed.
- Number of Subjects With <15% Progression in CAC Agatston Score From Baseline to Week 52 for Each Dose Group and the Combined Dose Groups vs Placebo [Baseline (Week 1, Day 1) and Week 52]
Agatston score is a semi-automated tool to calculate a score that reflects the extent of coronary artery calcification as detected by an unenhanced CT scan. Scores range from 0 to >1000 Agatston units where higher scores indicate an increased amount of calcification and an increased risk for a major adverse cardiac event. Change in Agatston Score values from baseline to Week 52 were calculated as a percentage of change (progression or worsening of calcification). The number of subjects with <15% progression were counted.
- Number of Subjects With >=15% Progression in CAC Agatston Score at Week 52 for Each Dose Group and the Combined Dose Groups vs Placebo [Baseline (Week 1, Day 1) and Week 52]
Agatston score is a semi-automated tool to calculate a score the reflects the extent of coronary artery calcification as detected by an unenhanced CT scan. Scores range from 0 to >1000 Agatston units where higher scores indicate an increased amount of calcification and an increased risk for a major adverse cardiac event. Change in Agatston Score values from baseline to Week 52 was calculated as a percentage of change (progression or worsening of calcification). The number of subjects with >=15% progression were counted for each treatment group, the combined treatments groups and placebo.
- Change in Log Thoracic Aorta Calcification Volume Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo [Baseline (Week 1, Day 1) and Week 52]
Coronary Artery Calcification (CAC) Volume Score is a calculation to quantify the calcification of coronary artery calcium without factoring in the calcium density as measured by the CAC Agatston Score. The CAC volume score observed in the thoracic aorta was used for this analysis. The CAC volume Score was log-transformed and the primary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for the combined dose groups and each dose group vs placebo. The secondary analysis used an ANCOVA model with the change in log volume score (log 52-week volume score - log baseline volume score) as the dependent variable and with a fixed effect term for the combined randomized treatment groups and log CAC volume score at baseline as a covariate. The least squares means for the treatment groups was estimated and back transformed. A smaller change from baseline to follow up is a better outcome.
- Change in Log Thoracic Aorta Calcification Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo [Baseline (Week 1, Day 1) and Week 52]
Coronary Artery Calcification (CAC) Agatston Score is a semi-automated tool to calculate a score that reflects the extent of coronary artery calcification as detected by an unenhanced CT scan. Scores range from 0 to >1000 Agatston units where higher scores indicate an increased amount of calcification and an increased risk for a major adverse cardiac event. This secondary outcome measure was the change in CAC Agatston Score in the thoracic aorta from Baseline to Week 52 for each dose group and the treated arms combined vs placebo. The analysis used an ANCOVA model with the change in log score (log 52-week score - log baseline score) as the dependent variable and with a fixed effect term for each randomized treatment groups and log CAC score at baseline as a covariate. The least squares means for each of the treatment groups separately and combined was estimated and back transformed. A smaller change from baseline to follow up is a better outcome.
- Change in Log Aortic Valve Calcification Volume Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo [Baseline (Week 1, Day 1) and Week 52]
Coronary Artery Calcification (CAC) Volume Score is a calculation to quantify the calcification of coronary artery calcium without factoring in the calcium density as measured by the CAC Agatston Score. The CAC volume score observed in the aortic valve was used for this analysis. The CAC volume Score was log-transformed and the primary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for the combined dose groups and each dose group vs placebo. The secondary analysis used an ANCOVA model with the change in log volume score (log 52-week volume score - log baseline volume score) as the dependent variable and with a fixed effect term for the combined randomized treatment groups and log CAC volume score at baseline as a covariate. The least squares means for the treatment groups was estimated and back transformed. A smaller change from baseline to follow up is a better outcome.
- Change in Log Aortic Valve Calcification Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo [Baseline (Week 1, Day 1) and Week 52]
Coronary Artery Calcification (CAC) Agatston Score is a semi-automated tool to calculate a score the reflects the extent of coronary artery calcification as detected by an unenhanced CT scan. Scores range from 0 to >1000 Agatston units where higher scores indicate an increased amount of calcification and an increased risk for a major adverse cardiac event. This secondary outcome measure was the change in Log CAC Agatston Score or the aortic valve from Baseline to Week 52 for each dose group and the treated arms combined vs placebo. The analysis used an ANCOVA model with the change in log score (log 52-week score - log baseline score) as the dependent variable and with a fixed effect term for each randomized treatment groups and log CAC score at baseline as a covariate. The least squares means for each of the treatment groups separately and combined was estimated and back transformed. A smaller change from baseline to follow up is a better outcome.
- Number of Participants With the Composite Safety Endpoint (Cardiovascular Death, Nonfatal Myocardial Infarction, Non-fatal Stroke, Heart Failure or Non-fatal Cardiac Arrest. [Baseline (Week 1, Day 1) and Week 52]
The number of subjects meeting this composite safety endpoint were counted and expressed by the randomized arm as a % of patients for the safety population.terms resulting in death from cardiovascular causes, myocardial infarction, stroke, or heart failure for each dose group and placebo were summarized .
- Mortality Rate (All-cause) for Each Dose Group and Placebo [Baseline (Week 1, Day 1) and Week 52]
The number of deaths were counted and expressed by the randomized arm as a % of patients for the safety population.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Female or male patients, 18 to 80 years (inclusive) of age at randomisation
-
CAC score of 100 to 3500 AU (Agatston Units) inclusive within a 3-week period prior to randomisation as measured by a multi-detector CT scanner
-
Patients who are EITHER ≥ 55 years OR have a history of diabetes mellitus at randomisation
-
Patients on HD for ≥ 6 months prior to randomisation
-
Willing and able to understand and sign the informed consent
Exclusion Criteria:
-
Scheduled date for kidney transplant from a known living donor
-
Weight above 300 lbs (136 kg)
-
Hospitalisation in the previous 3 months prior to randomisation for unstable angina, MI, stroke, transient ischaemic attack, amputation or peripheral or coronary bypass surgery
-
History of unstable heart failure in the previous 3 months, defined as an unplanned presentation to a hospital or dialysis treatment facility with signs/symptoms of acute pulmonary edema and requiring ultrafiltration therapy
-
History of cancer that has been in remission for < 5 years prior to randomisation. A history of basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin is allowed
-
Pregnant or trying to become pregnant, currently breast-feeding, or of child-bearing potential (including peri-menopausal women who have had a menstrual period within one year) and not willing to practice birth control using a double barrier method (criteria apply to women only) at least 30 days post last dose of study medication
-
Hypocalcaemia defined as a serum calcium below 8.0 mg/dL (or 2.0 mmol/L) for the serum calcium most proximal to screening per patient's medical records
-
Extreme elevation in serum phosphorous, defined as a serum phosphorous above 10 mg/dL (or 3.23 mmol/L) within the last 2 months proximal to screening per patient's medical records
-
Uncontrolled hypertension defined as any 2 or more consecutive post-dialysis diastolic blood pressure (DBP) > 100 mmHg within the last 2 months proximal to screening expected survival < 2 years in the Investigator's medical opinion
-
Known active drug or alcohol abuse within 1 year of randomisation
-
Use of other investigational drugs within 30 days of randomisation
-
Non-compliance with dialysis treatment which, in the opinion of the Investigator, evidenced by either repeated missed dialysis treatments or significant non-compliance with the patient's medication regimen
-
Inability to comply with all required study procedures and schedule, inability to speak and read in the protocol-derived language of that patient's clinical site, or unwillingness or inability to give written informed consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Bakersfield | California | United States | 93308 | |
| 2 | Chula Vista | California | United States | 91910 | |
| 3 | Escondido | California | United States | 92025 | |
| 4 | Granada Hills | California | United States | 91344 | |
| 5 | La Palma | California | United States | 90623 | |
| 6 | Long Beach | California | United States | 90807 | |
| 7 | Los Angeles | California | United States | 90048 | |
| 8 | Lynwood | California | United States | 90262 | |
| 9 | Northridge | California | United States | 91324 | |
| 10 | Riverside | California | United States | 92505 | |
| 11 | San Diego | California | United States | 92111 | |
| 12 | San Dimas | California | United States | 91773 | |
| 13 | Simi Valley | California | United States | 93065 | |
| 14 | Tarzana | California | United States | 91356 | |
| 15 | Whittier | California | United States | 90603 | |
| 16 | Arvada | Colorado | United States | 80002 | |
| 17 | Westminster | Colorado | United States | 80031 | |
| 18 | Middlebury | Connecticut | United States | 06762 | |
| 19 | Orange | Connecticut | United States | 06477 | |
| 20 | Hollywood | Florida | United States | 33024 | |
| 21 | Lauderdale Lakes | Florida | United States | 33313-1638 | |
| 22 | Miami Gardens | Florida | United States | 33169 | |
| 23 | Miami | Florida | United States | 33133 | |
| 24 | Ocala | Florida | United States | 34471 | |
| 25 | Tampa | Florida | United States | 33614 | |
| 26 | Evanston | Illinois | United States | 60201 | |
| 27 | Shreveport | Louisiana | United States | 71101 | |
| 28 | Pontiac | Michigan | United States | 48341 | |
| 29 | Roseville | Michigan | United States | 48066 | |
| 30 | Brookhaven | Mississippi | United States | 39601 | |
| 31 | Las Vegas | Nevada | United States | 89106 | |
| 32 | Reno | Nevada | United States | 89511 | |
| 33 | North Brunswick | New Jersey | United States | 08902 | |
| 34 | Bronx | New York | United States | 10461 | |
| 35 | College Point | New York | United States | 11356 | |
| 36 | Asheville | North Carolina | United States | 28801 | |
| 37 | Cincinnati | Ohio | United States | 45267 | |
| 38 | Bethlehem | Pennsylvania | United States | 18017 | |
| 39 | Knoxville | Tennessee | United States | 37923 | |
| 40 | Arlington | Texas | United States | 76015 | |
| 41 | Houston | Texas | United States | 77024 | |
| 42 | Houston | Texas | United States | 77099 | |
| 43 | Richardson | Texas | United States | 75080 | |
| 44 | San Antonio | Texas | United States | 78207 | |
| 45 | Chesapeake | Virginia | United States | 23320 | |
| 46 | Wauwatosa | Wisconsin | United States | 53226 | |
| 47 | Palma de Mallorca | Balearic Islands | Spain | 07198 | |
| 48 | Barcelona | Catalonia | Spain | 08025 | |
| 49 | Palma | Illes Balears | Spain | 07011 | |
| 50 | Palma | Islas Baleares | Spain | 07120 | |
| 51 | Galdakao | Vizcaya | Spain | 48960 | |
| 52 | Barcelona | Spain | 08003 | ||
| 53 | Barcelona | Spain | 08035 | ||
| 54 | Barcelona | Spain | 08036 | ||
| 55 | Barcelona | Spain | 08208 | ||
| 56 | Barcelona | Spain | 08970 | ||
| 57 | Córdoba | Spain | 14004 | ||
| 58 | Lleida | Spain | 25008 | ||
| 59 | Lleida | Spain | 25198 | ||
| 60 | Lugo | Spain | 27003 | ||
| 61 | Madrid | Spain | 28040 | ||
| 62 | Navarro | Spain | 31008 | ||
| 63 | Oviedo | Spain | 33011 | ||
| 64 | Palma | Spain | 07300 | ||
| 65 | Santander | Spain | 39008 | ||
| 66 | Sevilla | Spain | 41007 | ||
| 67 | Valencia | Spain | 46010 | ||
| 68 | Valencia | Spain | 46017 | ||
| 69 | Zaragoza | Spain | 50009 | ||
| 70 | Bradford | United Kingdom | BD5 0NA | ||
| 71 | Manchester | United Kingdom | M13 9WL | ||
| 72 | Salford | United Kingdom | M6 8HD | ||
| 73 | Shrewsbury | United Kingdom | SY3 8XQ | ||
| 74 | Swansea | United Kingdom | SA6 6NL | ||
| 75 | Westcliff-on-Sea | United Kingdom | SS0 0RY |
Sponsors and Collaborators
- Sanifit Therapeutics S. A.
- Clinipace Worldwide
Investigators
- Study Director: Alex Gold, MD, Sanifit Chief Medical Officer
Study Documents (Full-Text)
More Information
Publications
None provided.- SNFCT2015-05
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | Matching Placebo |
|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Period Title: Overall Study | |||
| STARTED | 92 | 91 | 91 |
| COMPLETED | 68 | 57 | 60 |
| NOT COMPLETED | 24 | 34 | 31 |
Baseline Characteristics
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | Matching Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Total of all reporting groups |
| Overall Participants | 92 | 91 | 90 | 273 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
54
58.7%
|
51
56%
|
40
44.4%
|
145
53.1%
|
| >=65 years |
38
41.3%
|
40
44%
|
50
55.6%
|
128
46.9%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
63
(9.5)
|
64
(8.9)
|
64.
(8.2)
|
63.5
(8.9)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
38
41.3%
|
36
39.6%
|
33
36.7%
|
107
39.2%
|
| Male |
54
58.7%
|
55
60.4%
|
57
63.3%
|
166
60.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
31
33.7%
|
36
39.6%
|
32
35.6%
|
99
36.3%
|
| Not Hispanic or Latino |
60
65.2%
|
51
56%
|
56
62.2%
|
167
61.2%
|
| Unknown or Not Reported |
1
1.1%
|
4
4.4%
|
2
2.2%
|
7
2.6%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
2
2.2%
|
0
0%
|
0
0%
|
2
0.7%
|
| Asian |
2
2.2%
|
4
4.4%
|
4
4.4%
|
10
3.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
1.1%
|
0
0%
|
1
0.4%
|
| Black or African American |
27
29.3%
|
15
16.5%
|
19
21.1%
|
61
22.3%
|
| White |
59
64.1%
|
67
73.6%
|
62
68.9%
|
188
68.9%
|
| More than one race |
1
1.1%
|
0
0%
|
0
0%
|
1
0.4%
|
| Unknown or Not Reported |
1
1.1%
|
4
4.4%
|
5
5.6%
|
10
3.7%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
58
63%
|
53
58.2%
|
54
60%
|
165
60.4%
|
| United Kingdom |
6
6.5%
|
3
3.3%
|
5
5.6%
|
14
5.1%
|
| Spain |
28
30.4%
|
35
38.5%
|
31
34.4%
|
94
34.4%
|
| CAC Agatston Score (units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units on a scale] |
917
(697)
|
963
(702)
|
965
(762)
|
948
(744)
|
Outcome Measures
| Title | Change in Log CAC Volume Score From Baseline to Week 52 for the Combined Dose Groups vs Placebo |
|---|---|
| Description | Coronary Artery Calcification (CAC) Volume Score is a calculation to quantify the calcification of coronary artery calcium without factoring in the calcium density as measured by the CAC Agatston Score. The CAC Score was log-transformed and the primary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for the combined dose groups vs placebo. The primary analysis used an ANCOVA model with the change in log volume score (log 52-week volume score - log baseline volume score) as the dependent variable and with a fixed effect term for the combined randomized treatment groups and log CAC volume score at baseline as a covariate. The least squares means for the treatment groups was estimated and back transformed. A smaller change from baseline to follow up is a better outcome. |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified intent-to-treat (mITT) population, last observation carried forward (LOCF) |
| Arm/Group Title | SNF472 300 mg & 600 mg Combined | Matching Placebo |
|---|---|---|
| Arm/Group Description | Dose (300 mg or 600 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) or 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 142 | 77 |
| Geometric Least Squares Mean (95% Confidence Interval) [ratio] |
1.11
|
1.20
|
| Title | Change in Log CAC Volume Score From Baseline to Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo |
|---|---|
| Description | Coronary Artery Calcification (CAC) Volume Score is a calculation to quantify the calcification of coronary artery calcium without factoring in the calcium density as measured by the CAC Agatston Score. The CAC Score was log-transformed and the primary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for the combined dose groups vs placebo. This secondary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for each dose group vs placebo. The analysis used an ANCOVA model with the change in log volume score (log 52-week volume score - log baseline volume score) as the dependent variable and with a fixed effect term for each randomized treatment groups and log CAC volume score at baseline as a covariate. The least squares means for each of the treatment groups was estimated and back transformed. A smaller change from baseline to follow up is a better outcome. |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified intent-to-treat (mITT) population, last observation carried forward (LOCF) |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | Matching Placebo |
|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 77 | 65 | 77 |
| Geometric Least Squares Mean (95% Confidence Interval) [ratio] |
1.12
|
1.10
|
1.20
|
| Title | Change in Log CAC Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and for the Combined Dose Groups vs the Placebo Group |
|---|---|
| Description | Coronary Artery Calcification (CAC) Agatston Score is a semi-automated tool to calculate a score the reflects the extent of coronary artery calcification as detected by an unenhanced CT scan. Scores range from 0 to >1000 Agatston units where higher scores indicate an increased amount of calcification and an increased risk for a major adverse cardiac event. This secondary outcome measure was the change in Log CAC Agatston Score from Baseline to Week 52 for each dose group and the treated arms combined vs placebo. The analysis used an ANCOVA model with the change in log score (log 52-week score - log baseline score) as the dependent variable and with a fixed effect term for each randomized treatment groups and log CAC score at baseline as a covariate. The least squares means for each of the treatment groups separately and combined was estimated and back transformed. |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified intent-to-treat (mITT) population, last observation carried forward (LOCF) |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | SNF 472 Combined Dose Groups | Matching Placebo |
|---|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Doses 300 and 600 mg. 1 vial of physiological saline and 1 vial of active or 2 vials of active(10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 77 | 65 | 142 | 77 |
| Geometric Least Squares Mean (95% Confidence Interval) [ratio] |
1.10
|
1.13
|
1.11
|
1.20
|
| Title | Number of Subjects With <15% Progression in CAC Agatston Score From Baseline to Week 52 for Each Dose Group and the Combined Dose Groups vs Placebo |
|---|---|
| Description | Agatston score is a semi-automated tool to calculate a score that reflects the extent of coronary artery calcification as detected by an unenhanced CT scan. Scores range from 0 to >1000 Agatston units where higher scores indicate an increased amount of calcification and an increased risk for a major adverse cardiac event. Change in Agatston Score values from baseline to Week 52 were calculated as a percentage of change (progression or worsening of calcification). The number of subjects with <15% progression were counted. |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified intent-to-treat (mITT) population, last observation carried forward (LOCF) |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | SNF 472 Combined Dose Groups | Matching Placebo |
|---|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Doses 300 and 600 mg. 1 vial of physiological saline and 1 vial of active or 2 vials of active(10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 77 | 65 | 142 | 77 |
| Count of Participants [Participants] |
46
50%
|
41
45.1%
|
87
96.7%
|
37
13.6%
|
| Title | Number of Subjects With >=15% Progression in CAC Agatston Score at Week 52 for Each Dose Group and the Combined Dose Groups vs Placebo |
|---|---|
| Description | Agatston score is a semi-automated tool to calculate a score the reflects the extent of coronary artery calcification as detected by an unenhanced CT scan. Scores range from 0 to >1000 Agatston units where higher scores indicate an increased amount of calcification and an increased risk for a major adverse cardiac event. Change in Agatston Score values from baseline to Week 52 was calculated as a percentage of change (progression or worsening of calcification). The number of subjects with >=15% progression were counted for each treatment group, the combined treatments groups and placebo. |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified intent-to-treat (mITT) population, last observation carried forward (LOCF) |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | SNF 472 Combined Dose Groups | Matching Placebo |
|---|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Doses 300 and 600 mg. 1 vial of physiological saline and 1 vial of active or 2 vials of active(10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 77 | 65 | 142 | 77 |
| Count of Participants [Participants] |
31
33.7%
|
24
26.4%
|
55
61.1%
|
40
14.7%
|
| Title | Change in Log Thoracic Aorta Calcification Volume Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo |
|---|---|
| Description | Coronary Artery Calcification (CAC) Volume Score is a calculation to quantify the calcification of coronary artery calcium without factoring in the calcium density as measured by the CAC Agatston Score. The CAC volume score observed in the thoracic aorta was used for this analysis. The CAC volume Score was log-transformed and the primary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for the combined dose groups and each dose group vs placebo. The secondary analysis used an ANCOVA model with the change in log volume score (log 52-week volume score - log baseline volume score) as the dependent variable and with a fixed effect term for the combined randomized treatment groups and log CAC volume score at baseline as a covariate. The least squares means for the treatment groups was estimated and back transformed. A smaller change from baseline to follow up is a better outcome. |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified intent-to-treat (mITT) population, last observation carried forward (LOCF) |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | SNF 472 Combined Dose Groups | Matching Placebo |
|---|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Doses 300 and 600 mg. 1 vial of physiological saline and 1 vial of active or 2 vials of active(10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 74 | 60 | 134 | 75 |
| Geometric Least Squares Mean (95% Confidence Interval) [ratio] |
1.25
|
1.21
|
1.23
|
1.28
|
| Title | Change in Log Thoracic Aorta Calcification Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo |
|---|---|
| Description | Coronary Artery Calcification (CAC) Agatston Score is a semi-automated tool to calculate a score that reflects the extent of coronary artery calcification as detected by an unenhanced CT scan. Scores range from 0 to >1000 Agatston units where higher scores indicate an increased amount of calcification and an increased risk for a major adverse cardiac event. This secondary outcome measure was the change in CAC Agatston Score in the thoracic aorta from Baseline to Week 52 for each dose group and the treated arms combined vs placebo. The analysis used an ANCOVA model with the change in log score (log 52-week score - log baseline score) as the dependent variable and with a fixed effect term for each randomized treatment groups and log CAC score at baseline as a covariate. The least squares means for each of the treatment groups separately and combined was estimated and back transformed. A smaller change from baseline to follow up is a better outcome. |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified intent-to-treat (mITT) population, last observation carried forward (LOCF) |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | SNF 472 Combined Dose Groups | Matching Placebo |
|---|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Doses 300 and 600 mg. 1 vial of physiological saline and 1 vial of active or 2 vials of active(10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 74 | 60 | 134 | 75 |
| Geometric Least Squares Mean (95% Confidence Interval) [ratio] |
1.30
|
1.28
|
1.29
|
1.32
|
| Title | Change in Log Aortic Valve Calcification Volume Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo |
|---|---|
| Description | Coronary Artery Calcification (CAC) Volume Score is a calculation to quantify the calcification of coronary artery calcium without factoring in the calcium density as measured by the CAC Agatston Score. The CAC volume score observed in the aortic valve was used for this analysis. The CAC volume Score was log-transformed and the primary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for the combined dose groups and each dose group vs placebo. The secondary analysis used an ANCOVA model with the change in log volume score (log 52-week volume score - log baseline volume score) as the dependent variable and with a fixed effect term for the combined randomized treatment groups and log CAC volume score at baseline as a covariate. The least squares means for the treatment groups was estimated and back transformed. A smaller change from baseline to follow up is a better outcome. |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | SNF 472 Combined Dose Groups | Matching Placebo |
|---|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Doses 300 and 600 mg. 1 vial of physiological saline and 1 vial of active or 2 vials of active(10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 75 | 63 | 138 | 69 |
| Geometric Least Squares Mean (95% Confidence Interval) [ratio] |
1.28
|
1.01
|
1.14
|
1.98
|
| Title | Change in Log Aortic Valve Calcification Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo |
|---|---|
| Description | Coronary Artery Calcification (CAC) Agatston Score is a semi-automated tool to calculate a score the reflects the extent of coronary artery calcification as detected by an unenhanced CT scan. Scores range from 0 to >1000 Agatston units where higher scores indicate an increased amount of calcification and an increased risk for a major adverse cardiac event. This secondary outcome measure was the change in Log CAC Agatston Score or the aortic valve from Baseline to Week 52 for each dose group and the treated arms combined vs placebo. The analysis used an ANCOVA model with the change in log score (log 52-week score - log baseline score) as the dependent variable and with a fixed effect term for each randomized treatment groups and log CAC score at baseline as a covariate. The least squares means for each of the treatment groups separately and combined was estimated and back transformed. A smaller change from baseline to follow up is a better outcome. |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified intent-to-treat (mITT) population, last observation carried forward (LOCF) |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | SNF 472 Combined Dose Groups | Matching Placebo |
|---|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Doses 300 and 600 mg. 1 vial of physiological saline and 1 vial of active or 2 vials of active(10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 75 | 63 | 138 | 69 |
| Geometric Least Squares Mean (95% Confidence Interval) [ratio] |
1.33
|
0.98
|
1.14
|
2.86
|
| Title | Number of Participants With the Composite Safety Endpoint (Cardiovascular Death, Nonfatal Myocardial Infarction, Non-fatal Stroke, Heart Failure or Non-fatal Cardiac Arrest. |
|---|---|
| Description | The number of subjects meeting this composite safety endpoint were counted and expressed by the randomized arm as a % of patients for the safety population.terms resulting in death from cardiovascular causes, myocardial infarction, stroke, or heart failure for each dose group and placebo were summarized . |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | SNF 472 Combined Dose Groups | Matching Placebo |
|---|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Doses 300 and 600 mg. 1 vial of physiological saline and 1 vial of active or 2 vials of active(10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 92 | 91 | 183 | 90 |
| Count of Participants [Participants] |
7
7.6%
|
6
6.6%
|
13
14.4%
|
10
3.7%
|
| Title | Mortality Rate (All-cause) for Each Dose Group and Placebo |
|---|---|
| Description | The number of deaths were counted and expressed by the randomized arm as a % of patients for the safety population. |
| Time Frame | Baseline (Week 1, Day 1) and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | SNF 472 Combined Dose Groups | Matching Placebo |
|---|---|---|---|---|
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Doses 300 and 600 mg. 1 vial of physiological saline and 1 vial of active or 2 vials of active(10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. |
| Measure Participants | 92 | 91 | 183 | 90 |
| Count of Participants [Participants] |
1
1.1%
|
6
6.6%
|
7
7.8%
|
5
1.8%
|
Adverse Events
| Time Frame | Collected over one year | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | SNF472 300 mg | SNF 472 600 mg | Matching Placebo | |||
| Arm/Group Description | Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL) SNF472: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | Placebo arm: 2 vials of physiological saline Placebo: Administered 3 times weekly by intravenous infusion through the dialysis machine in conjunction with the patient's dialysis sessions. | |||
All Cause Mortality |
||||||
| SNF472 300 mg | SNF 472 600 mg | Matching Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/92 (1.1%) | 6/91 (6.6%) | 5/90 (5.6%) | |||
Serious Adverse Events |
||||||
| SNF472 300 mg | SNF 472 600 mg | Matching Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 38/92 (41.3%) | 55/91 (60.4%) | 49/90 (54.4%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 2/90 (2.2%) | 2 |
| Agranulocytosis | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Anaemia of chronic disease | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Coagulopathy | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Haemorrhagic anaemia | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Nephrogenic anaemia | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Cardiac disorders | ||||||
| Atrial fibrillation | 3/92 (3.3%) | 3 | 3/91 (3.3%) | 3 | 2/90 (2.2%) | 2 |
| Acute myocardial infarction | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 4/90 (4.4%) | 4 |
| Cardiac arrest | 1/92 (1.1%) | 1 | 3/91 (3.3%) | 3 | 0/90 (0%) | 0 |
| Atrial flutter | 0/92 (0%) | 0 | 3/91 (3.3%) | 3 | 0/90 (0%) | 0 |
| Arteriosclerosis coronary artery | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Cardiac failure | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 2/90 (2.2%) | 2 |
| Coronary artery disease | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Angina unstable | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Aortic valve stenosis | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Atrioventricular block complete | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Cardiac failure congestive | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Cardiogenic shock | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Coronary artery stenosis | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Hypertensive heart disease | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Left ventricular failure | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Mitral valve incompetence | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Myocardial infarction | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Sinus node dysfunction | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Eye disorders | ||||||
| Retinal detachment | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Vitreous haemorrhage | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Gastrointestinal disorders | ||||||
| Gastrointestinal haemorrhage | 0/92 (0%) | 0 | 4/91 (4.4%) | 4 | 0/90 (0%) | 0 |
| Pancreatitis acute | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Abdominal pain | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 2/90 (2.2%) | 2 |
| Colitis ischaemic | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Abdominal hernia | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Abdominal mass | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Ascites | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Diabetic gastroparesis | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Diarrhoea | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Gastrointestinal necrosis | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Gastrointestinal ulcer haemorrhage | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Haemorrhoidal haemorrhage | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Impaired gastric emptying | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Inguinal hernia | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Rectal haemorrhage | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Ulcerative gastritis | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| General disorders | ||||||
| Chest pain | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 3/90 (3.3%) | 3 |
| Pyrexia | 0/92 (0%) | 0 | 3/91 (3.3%) | 3 | 0/90 (0%) | 0 |
| Multiple organ dysfunction syndrome | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Asthenia | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Non-cardiac chest pain | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Systemic inflammatory response syndrome | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Acute hepatic failure | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Cholecystitis acute | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Cholecystitis | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Cholelithiasis | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Drug-induced liver injury | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Hepatic ischaemia | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Hepatitis acute | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Infections and infestations | ||||||
| Pneumonia | 4/92 (4.3%) | 4 | 3/91 (3.3%) | 3 | 7/90 (7.8%) | 7 |
| Sepsis | 2/92 (2.2%) | 2 | 2/91 (2.2%) | 2 | 1/90 (1.1%) | 1 |
| Cellulitis | 2/92 (2.2%) | 2 | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Septic shock | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Staphylococcal bacteraemia | 2/92 (2.2%) | 2 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Arteriovenous graft site infection | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Bronchitis | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Device related infection | 0/92 (0%) | 0 | 2/91 (2.2%) | 2 | 0/90 (0%) | 0 |
| Endocarditis | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Gangrene | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Respiratory tract infection | 0/92 (0%) | 0 | 2/91 (2.2%) | 2 | 0/90 (0%) | 0 |
| Urinary tract infection | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Arteriovenous graft site abscess | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Arthritis infective | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Bacteraemia | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Clostridium difficile colitis | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Diabetic foot infection | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Diverticulitis | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Emphysematous cystitis | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Enterocolitis viral | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Gastroenteritis | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Gastroenteritis bacterial | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Herpes zoster | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Influenza | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Localised infection | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Osteomyelitis bacterial | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Pseudomonas infection | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Urosepsis | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Vascular access site infection | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Wound infection | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Wound infection pseudomonas | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Clostridium difficile infection | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Arteriovenous fistula site complication | 1/92 (1.1%) | 1 | 3/91 (3.3%) | 3 | 1/90 (1.1%) | 1 |
| Arteriovenous fistula thrombosis | 2/92 (2.2%) | 2 | 0/91 (0%) | 0 | 2/90 (2.2%) | 2 |
| Hip fracture | 0/92 (0%) | 0 | 2/91 (2.2%) | 2 | 2/90 (2.2%) | 2 |
| Vascular graft complication | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 2/90 (2.2%) | 2 |
| Ankle fracture | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Arterial injury | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Arteriovenous fistula site haematoma | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Arteriovenous fistula site haemorrhage | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Arteriovenous graft aneurysm | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Arteriovenous graft thrombosis | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Fall | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Femoral neck fracture | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Fractured sacrum | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Limb injury | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Lower limb fracture | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Post procedural complication | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Post procedural haemorrhage | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Procedural hypotension | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Tendon rupture | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Toxicity to various agents | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Upper limb fracture | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Investigations | ||||||
| Blood lactic acid increased | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Cardiac stress test abnormal | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Influenza a virus test positive | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| International normalised ratio increased | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Myocardial necrosis marker increased | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Stress echocardiogram abnormal | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Troponin increased | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Fluid overload | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 3/90 (3.3%) | 3 |
| Hyperkalaemia | 2/92 (2.2%) | 2 | 1/91 (1.1%) | 1 | 2/90 (2.2%) | 2 |
| Hyperglycaemia | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Hypoglycaemia | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Calciphylaxis | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Diabetes mellitus inadequate control | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Malnutrition | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Pain in extremity | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Arthralgia | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Musculoskeletal pain | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Colon cancer | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Large intestine benign neoplasm | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Nervous system disorders | ||||||
| Metabolic encephalopathy | 2/92 (2.2%) | 2 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Transient ischaemic attack | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 2/90 (2.2%) | 2 |
| Ischaemic stroke | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Loss of consciousness | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Cognitive disorder | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Dizziness postural | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Epilepsy | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Myasthenia gravis | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Seizure | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Syncope | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Uraemic encephalopathy | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Psychiatric disorders | ||||||
| Mental status changes | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Renal mass | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Urinary retention | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute pulmonary oedema | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Acute respiratory failure | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Asthma | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Respiratory distress | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Respiratory failure | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Chronic obstructive pulmonary disease | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Dyspnoea | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Haemoptysis | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Pleural effusion | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Pneumonitis | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Pulmonary embolism | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Pulmonary oedema | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Surgical and medical procedures | ||||||
| Renal Transplant | 6/92 (6.5%) | 6 | 14/91 (15.4%) | 14 | 11/90 (12.2%) | 11 |
| Lymphadenectomy | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Toe amputation | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Vascular disorders | ||||||
| Hypotension | 3/92 (3.3%) | 3 | 2/91 (2.2%) | 2 | 1/90 (1.1%) | 1 |
| Hypertension | 1/92 (1.1%) | 1 | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Haematoma | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 1/90 (1.1%) | 1 |
| Hypertensive crisis | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
| Peripheral vascular disorder | 0/92 (0%) | 0 | 2/91 (2.2%) | 2 | 0/90 (0%) | 0 |
| Aortic stenosis | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Deep vein thrombosis | 0/92 (0%) | 0 | 1/91 (1.1%) | 1 | 0/90 (0%) | 0 |
| Foreign body embolism | 1/92 (1.1%) | 1 | 0/91 (0%) | 0 | 0/90 (0%) | 0 |
| Peripheral ischaemia | 0/92 (0%) | 0 | 0/91 (0%) | 0 | 1/90 (1.1%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| SNF472 300 mg | SNF 472 600 mg | Matching Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 62/92 (67.4%) | 64/91 (70.3%) | 67/90 (74.4%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 7/92 (7.6%) | 7 | 11/91 (12.1%) | 11 | 10/90 (11.1%) | 10 |
| Abdominal pain upper | 11/92 (12%) | 11 | 2/91 (2.2%) | 2 | 2/90 (2.2%) | 2 |
| Vomiting | 1/92 (1.1%) | 1 | 8/91 (8.8%) | 8 | 4/90 (4.4%) | 4 |
| Nausea | 2/92 (2.2%) | 2 | 5/91 (5.5%) | 5 | 4/90 (4.4%) | 4 |
| Infections and infestations | ||||||
| Upper respiratory tract infection | 2/92 (2.2%) | 2 | 4/91 (4.4%) | 4 | 6/90 (6.7%) | 6 |
| Nasopharyngitis | 3/92 (3.3%) | 3 | 1/91 (1.1%) | 1 | 6/90 (6.7%) | 6 |
| Musculoskeletal and connective tissue disorders | ||||||
| Pain in extremity | 7/92 (7.6%) | 7 | 7/91 (7.7%) | 7 | 7/90 (7.8%) | 7 |
| Musculoskeletal pain | 3/92 (3.3%) | 3 | 6/91 (6.6%) | 6 | 5/90 (5.6%) | 5 |
| Back pain | 6/92 (6.5%) | 6 | 2/91 (2.2%) | 2 | 4/90 (4.4%) | 4 |
| Arthralgia | 5/92 (5.4%) | 5 | 2/91 (2.2%) | 2 | 4/90 (4.4%) | 4 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 10/92 (10.9%) | 10 | 9/91 (9.9%) | 9 | 8/90 (8.9%) | 8 |
| Dyspnoea | 5/92 (5.4%) | 5 | 7/91 (7.7%) | 7 | 7/90 (7.8%) | 7 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | SVP Clinical Development Operations |
|---|---|
| Organization | Sanifit |
| Phone | 18582815976 |
| Claire.Padgett@sanifit.com |
- SNFCT2015-05