Trial Outcomes & Findings for The Effect of RNS60 on ALS Biomarkers (NCT NCT03456882)
NCT ID: NCT03456882
Last Updated: 2023-04-21
Results Overview
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
147 participants
Primary outcome timeframe
24 weeks (week 0 - week 24)
Results posted on
2023-04-21
Participant Flow
Trial participants were enrolled at 22 Italian Expert ALS Centers from May 2017 to January 2020
We enrolled 5 patients more than what was planned in the protocol.
Participant milestones
| Measure |
RNS60
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Overall Study
STARTED
|
74
|
73
|
|
Overall Study
COMPLETED
|
60
|
50
|
|
Overall Study
NOT COMPLETED
|
14
|
23
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Effect of RNS60 on ALS Biomarkers
Baseline characteristics by cohort
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
Total
n=147 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.3 years
STANDARD_DEVIATION 10.4 • n=99 Participants
|
56.0 years
STANDARD_DEVIATION 10.0 • n=107 Participants
|
57.7 years
STANDARD_DEVIATION 10.3 • n=206 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
48 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
52 Participants
n=99 Participants
|
47 Participants
n=107 Participants
|
99 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
74 Participants
n=99 Participants
|
73 Participants
n=107 Participants
|
147 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
Italy
|
74 participants
n=99 Participants
|
73 participants
n=107 Participants
|
147 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 24 weeks (week 0 - week 24)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: MCP-1 On-treatment Period Variation
|
4.6 pg/ml
Standard Error 1.8
|
2.2 pg/ml
Standard Error 1.9
|
PRIMARY outcome
Timeframe: 24 weeks (week 0 - week 24)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: Cyp-A On-treatment Period Variation
|
6.6 pg/ml
Standard Error 14.3
|
6.9 pg/ml
Standard Error 14.4
|
PRIMARY outcome
Timeframe: 24 weeks (week 0 - week 24)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: Actin-NT On-treatment Period Variation
|
9.4 pg/ml
Standard Error 10
|
2.9 pg/ml
Standard Error 10.2
|
PRIMARY outcome
Timeframe: 24 weeks (week 0 - week 24)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: 3-NT On-treatment Period Variation
|
14.3 pg/ml
Standard Error 13.8
|
-2.4 pg/ml
Standard Error 14.1
|
PRIMARY outcome
Timeframe: 24 weeks (week 0 - week 24)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: IL-17 On-treatment Period Variation
|
0.12 pg/ml
Standard Error 0.15
|
0.39 pg/ml
Standard Error 0.15
|
PRIMARY outcome
Timeframe: 24 weeks (week 0 - week 24)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: Nfl On-treatment Period Variation
|
2.7 pg/ml
Standard Error 2.6
|
5.6 pg/ml
Standard Error 2.7
|
PRIMARY outcome
Timeframe: 24 weeks (week 0 - week 24)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: FOXP3 mRNA On-treatment Period Variation
|
-0.14 pg/ml
Standard Error 0.18
|
-0.20 pg/ml
Standard Error 0.18
|
PRIMARY outcome
Timeframe: 24 weeks (week 0 - week 24)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
1\. To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: CD25 mRNA On-treatment Period Variation
|
-0.01 pg/ml
Standard Error 0.08
|
-0.10 pg/ml
Standard Error 0.09
|
SECONDARY outcome
Timeframe: 24 weeks on-treatment period (week 0 - week 24) + 24 weeks off-treatment follow-up period (week 24 - week 48)Population: Intention to Treat population (all randomized subjects)
\*\*ALSFRS-R = ALS Functional Rating Scale - Revised\*\* The mean change of ALSFRS-R (\*\*min score 0 corresponding to maximum functional impairment - max score 48 corresponding to no functional impairment; higher score = better outcome\*\*) over the on-treatment period and the off-treatment follow-up period. Measured at weeks 0, 4, 12, 24, 36, 48.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
ALSFRS-R On-treatment and Off-treatment Variation
Slope on-treatment period (change per week from baseline to week 24)
|
-0.26 Score on a scale per week
Standard Error 0.03
|
-0.28 Score on a scale per week
Standard Error 0.03
|
|
ALSFRS-R On-treatment and Off-treatment Variation
Slope off-treatment follow-up period (change per week from week 24 to week 48)
|
-0.26 Score on a scale per week
Standard Error 0.03
|
-0.24 Score on a scale per week
Standard Error 0.03
|
SECONDARY outcome
Timeframe: 24 weeks on-treatment period (week 0 - week 24) + 24 weeks off-treatment follow-up period (week 24 - week 48)Population: Intention to Treat population (all randomized subjects)
The cumulative survival probability at 4, 12, 24, 36 and 48 weeks in the two treatment arms.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Survival
Week 48
|
7 Participants
|
6 Participants
|
|
Survival
Week 4
|
0 Participants
|
0 Participants
|
|
Survival
Week 12
|
0 Participants
|
1 Participants
|
|
Survival
Week 24
|
0 Participants
|
1 Participants
|
|
Survival
Week 36
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 24 weeks on-treatment period (week 0 - week 24) + 24 weeks off-treatment follow-up period (week 24 - week 48)Population: Intention to Treat population (all randomized subjects)
The mean change of Forced Vital Capacity percent value (FVC%) over the on-treatment period and the off-treatment follow-up period. Measured at weeks 0, 4, 12, 24, 36, 48.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
FVC% On-treatment and Off-treatment Variation
Slope on-treatment period (change per week from baseline to week 24)
|
-0.46 percent predicted/weeks
Standard Error 0.11
|
-0.87 percent predicted/weeks
Standard Error 0.1
|
|
FVC% On-treatment and Off-treatment Variation
Slope off-treatment follow-up period (change per week from week 24 to week 48)
|
-0.45 percent predicted/weeks
Standard Error 0.11
|
-0.54 percent predicted/weeks
Standard Error 0.13
|
SECONDARY outcome
Timeframe: 24 weeks on-treatment periodPopulation: Intention to Treat population (all randomized subjects)
The total number of subjects in the two treatment arms experiencing at least one adverse event (AE) leading to treatment discontinuation at 4, 12 and 24 weeks
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
AE Leading to Treatment Discontinuation
week 4
|
0 Participants
|
0 Participants
|
|
AE Leading to Treatment Discontinuation
week 12
|
0 Participants
|
1 Participants
|
|
AE Leading to Treatment Discontinuation
week 24
|
0 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 24 weeks on-treatment period (week 0 - week 24) + 24 weeks off-treatment follow-up period (week 24 - week 48)Population: Intention to Treat population (all randomized subjects)
\*\*ALSAQ-40=ALS Assessment Questionnaire - 40 items\*\* The mean change of ALSAQ-40 over the on-treatment period and the off-treatment follow-up period. Measured at weeks 0, 24, 48. The ALSAQ-40 is a 40-item questionnaire measuring health status and health related quality of life in ALS patients. It is divided in 5 domains: the physical mobility (it addresses problems of mobility); the ADL (activities of daily living) and independence (it addresses a variety of limitations in ADL); the eating and drinking (it adresses problems eating solid foods, swallowing and drinking liquids); the communication (it addresses a variety of problems in communicating with others); the emotional reactions (it addresses various emotional problems). \*\* For each domain the score has the following range: Min score =0 corresponding to the better condition - max score =100 corresponding to the worse condition. (A higher score corresponds to a better outcome ) \*\*
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
ALSAQ-40 Scale
ALSAQ-40 physical mobility domain
|
0.45 Score on a scale per week
Standard Error 0.1
|
0.58 Score on a scale per week
Standard Error 0.1
|
|
ALSAQ-40 Scale
ADL and independence domain
|
0.47 Score on a scale per week
Standard Error 0.06
|
0.59 Score on a scale per week
Standard Error 0.1
|
|
ALSAQ-40 Scale
eating and drinking domain
|
0.19 Score on a scale per week
Standard Error 0.1
|
0.38 Score on a scale per week
Standard Error 0.1
|
|
ALSAQ-40 Scale
communication domain
|
0.29 Score on a scale per week
Standard Error 0.1
|
0.33 Score on a scale per week
Standard Error 0.1
|
|
ALSAQ-40 Scale
emotional reactions domain
|
0.18 Score on a scale per week
Standard Error 0.1
|
0.25 Score on a scale per week
Standard Error 0.1
|
SECONDARY outcome
Timeframe: 24 weeks (week 24 - week 48)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: MCP-1 Off-treatment Period Variation
|
1.1 pg/ml
Standard Error 2.6
|
-0.2 pg/ml
Standard Error 3.8
|
SECONDARY outcome
Timeframe: 24 weeks (week 24 - week 48)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: Cyp-A Off-treatment Period Variation
|
16.0 pg/ml
Standard Error 16.4
|
-12.5 pg/ml
Standard Error 16.7
|
SECONDARY outcome
Timeframe: 24 weeks (week 24 - week 48)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: Actin-NT Off-treatment Period Variation
|
-4.8 pg/ml
Standard Error 11
|
2.9 pg/ml
Standard Error 11.2
|
SECONDARY outcome
Timeframe: 24 weeks (week 24 - week 48)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: 3-NT Off-treatment Period Variation
|
-26.3 pg/ml
Standard Error 14.6
|
-7.3 pg/ml
Standard Error 15.1
|
SECONDARY outcome
Timeframe: 24 weeks (week 24 - week 48)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: IL-17 Off-treatment Period Variation
|
-0.15 pg/ml
Standard Error 0.15
|
-0.11 pg/ml
Standard Error 0.16
|
SECONDARY outcome
Timeframe: 24 weeks (week 24 - week 48)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: FOXP3 mRNA Off-treatment Period Variation
|
-0.55 pg/ml
Standard Error 0.22
|
-0.15 pg/ml
Standard Error 0.23
|
SECONDARY outcome
Timeframe: 24 weeks (week 24 - week 48)Population: Mean change of plasma levels of Monocyte Chemoattractant Protein-1 (MCP-1) during the on-treatment period (from baseline to week 24). Measured at weeks 0, 4, 12, 24.
1\. To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Pharmacodynamic Biomarkers: CD25 mRNA Off-treatment Period Variation
|
0.21 pg/ml
Standard Error 0.11
|
0.11 pg/ml
Standard Error 0.11
|
SECONDARY outcome
Timeframe: 24 weeks on-treatment period (week 0 - week 24) + 24 weeks off-treatment follow-up period (week 24 - week 48)Population: Intention to Treat population (all randomized subjects)
The mean number of AEs per treatment arm at 4, 12, 24 and 48 weeks
Outcome measures
| Measure |
RNS60
n=74 Participants
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 Participants
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Mean Number of AE
week 24
|
1.7 Adverse events
Standard Deviation 2.6
|
2 Adverse events
Standard Deviation 3.6
|
|
Mean Number of AE
week 48
|
1.9 Adverse events
Standard Deviation 2.8
|
2.1 Adverse events
Standard Deviation 3.6
|
|
Mean Number of AE
week 4
|
0.4 Adverse events
Standard Deviation 0.8
|
0.5 Adverse events
Standard Deviation 1.1
|
|
Mean Number of AE
week 12
|
1 Adverse events
Standard Deviation 1.6
|
1.2 Adverse events
Standard Deviation 2.4
|
Adverse Events
RNS60
Serious events: 5 serious events
Other events: 44 other events
Deaths: 7 deaths
NORMAL SALINE
Serious events: 5 serious events
Other events: 48 other events
Deaths: 6 deaths
Serious adverse events
| Measure |
RNS60
n=74 participants at risk
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 participants at risk
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
BRONCHIAL OBSTRUCTION
|
0.00%
0/74 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
1.4%
1/73 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHOPNEUMONIA
|
0.00%
0/74 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
1.4%
1/73 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.00%
0/74 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
1.4%
1/73 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Injury, poisoning and procedural complications
FALL
|
1.4%
1/74 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
0.00%
0/73 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Injury, poisoning and procedural complications
FRACTURE
|
0.00%
0/74 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
1.4%
1/73 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Cardiac disorders
HEART ATTACK
|
1.4%
1/74 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
0.00%
0/73 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Vascular disorders
HYPERTENSION
|
1.4%
1/74 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
0.00%
0/73 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Hepatobiliary disorders
PANCREATITIS
|
0.00%
0/74 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
1.4%
1/73 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONIA
|
1.4%
1/74 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
1.4%
1/73 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY INFECTION
|
1.4%
1/74 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
0.00%
0/73 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Nervous system disorders
SYNCOPE
|
1.4%
1/74 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
0.00%
0/73 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
Other adverse events
| Measure |
RNS60
n=74 participants at risk
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
RNS60: normal saline plus oxigen in nanobubble
|
NORMAL SALINE
n=73 participants at risk
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
RNS60: normal saline plus oxigen in nanobubble
|
|---|---|---|
|
Gastrointestinal disorders
ABDOMINAL COLIC
|
10.8%
8/74 • Number of events 8 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
2.7%
2/73 • Number of events 2 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Gastrointestinal disorders
ACHALASIA EVENT
|
6.8%
5/74 • Number of events 5 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
0.00%
0/73 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHITIS
|
5.4%
4/74 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
0.00%
0/73 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
General disorders
CHILLS
|
5.4%
4/74 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
1.4%
1/73 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Skin and subcutaneous tissue disorders
DERMATITIS
|
10.8%
8/74 • Number of events 8 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
5.5%
4/73 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Gastrointestinal disorders
DIARREHA
|
5.4%
4/74 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
1.4%
1/73 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Injury, poisoning and procedural complications
FALL
|
8.1%
6/74 • Number of events 6 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
6.8%
5/73 • Number of events 5 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
General disorders
FLU
|
14.9%
11/74 • Number of events 11 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
15.1%
11/73 • Number of events 11 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Injury, poisoning and procedural complications
FRACTURE
|
2.7%
2/74 • Number of events 2 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
8.2%
6/73 • Number of events 6 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Nervous system disorders
HEADACHE
|
9.5%
7/74 • Number of events 7 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
15.1%
11/73 • Number of events 11 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Injury, poisoning and procedural complications
HEMATOMA
|
5.4%
4/74 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
1.4%
1/73 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Vascular disorders
HYPERTENSION
|
5.4%
4/74 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
5.5%
4/73 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Musculoskeletal and connective tissue disorders
JOINT PAIN
|
9.5%
7/74 • Number of events 7 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
1.4%
1/73 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Musculoskeletal and connective tissue disorders
LUMBOSCIATALGIA
|
0.00%
0/74 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
6.8%
5/73 • Number of events 5 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
General disorders
MALAISE
|
8.1%
6/74 • Number of events 6 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
5.5%
4/73 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
2.7%
2/74 • Number of events 2 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
5.5%
4/73 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
Gastrointestinal disorders
NAUSEA
|
1.4%
1/74 • Number of events 1 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
5.5%
4/73 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
|
General disorders
TEMPERATURE
|
5.4%
4/74 • Number of events 4 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
9.6%
7/73 • Number of events 7 • 24 weeks on-treatment period + 24 weeks off-treatment follow-up period
|
Additional Information
Elisabetta Pupillo
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Phone: +390239014605
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place