Trial Outcomes & Findings for A Pilot Study of RNS60 in Amyotrophic Lateral Sclerosis (ALS) (NCT NCT02525471)
NCT ID: NCT02525471
Last Updated: 2021-05-28
Results Overview
Safety will be assessed by the occurrence of adverse events over the course of 24 weeks of treatment plus the 4 week off-drug follow-up period (total of 28 weeks). Per the protocol, the first treatment was administered at Baseline (Day 0) and the 24th treatment was administered at Week 23 (Day 161), and a safety phone call performed at Week 28 (Day 196).
COMPLETED
PHASE1
24 participants
28 weeks
2021-05-28
Participant Flow
Participant milestones
| Measure |
RNS60
RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.
|
|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
Randomized/Treated
|
16
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
RNS60
RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.
|
|---|---|
|
Overall Study
Screen Failure
|
6
|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
Death
|
1
|
Baseline Characteristics
A Pilot Study of RNS60 in Amyotrophic Lateral Sclerosis (ALS)
Baseline characteristics by cohort
| Measure |
RNS60
n=16 Participants
RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.
|
|---|---|
|
Age, Continuous
|
52.9 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
|
Disease Onset
Bulbar onset
|
3 Participants
n=5 Participants
|
|
Disease Onset
Limb onset
|
12 Participants
n=5 Participants
|
|
Disease Onset
Other onset
|
1 Participants
n=5 Participants
|
|
Slow Vital Capacity
|
63.8 Max % predicted
n=5 Participants
|
|
ALS Functional Rating Scale - Revised
|
34.1 units on a scale
n=5 Participants
|
|
Riluzole Use
|
16 Participants
n=5 Participants
|
|
Months Since Symptom Onset
|
30.3 months
n=5 Participants
|
PRIMARY outcome
Timeframe: 28 weeksSafety will be assessed by the occurrence of adverse events over the course of 24 weeks of treatment plus the 4 week off-drug follow-up period (total of 28 weeks). Per the protocol, the first treatment was administered at Baseline (Day 0) and the 24th treatment was administered at Week 23 (Day 161), and a safety phone call performed at Week 28 (Day 196).
Outcome measures
| Measure |
RNS60
n=16 Participants
RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.
|
|---|---|
|
Safety as Measured by the Number of Participants Experiencing Adverse Events
|
16 Participants
|
PRIMARY outcome
Timeframe: 24 weeksTolerability will be defined as the ability of subjects to complete the entire 24-week study on study drug. Per the protocol, the first treatment was administered on Day 0 (Baseline) and the 24th treatment was administered at Week 23.
Outcome measures
| Measure |
RNS60
n=16 Participants
RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.
|
|---|---|
|
Tolerability to Complete the Entire 24 Week Study on Study Drug
|
13 Participants
|
PRIMARY outcome
Timeframe: 24 WeeksPopulation: Eleven (11) subjects participated in the imaging sub-study. Blood biomarkers were collected in a selected subset of subjects per protocol inclusion and exclusion criteria. Samples not collected were due to tech difficulties.
Selected biomarkers of inflammation were measured at Baseline and Week 23 on a sub-set of subjects. Biomarkers included IL-17 plasma levels and FOXP3 mRNA expression in whole blood, a marker of Treg function. Per the protocol, the first treatment was administered on Day 0 (Baseline) and the 24th treatment was administered on Day 161 (Week 23).
Outcome measures
| Measure |
RNS60
n=11 Participants
RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.
|
|---|---|
|
Blood Biomarkers of Inflammation.
IL-17 change at Week 24
|
-25.4 pg/ml
Standard Deviation 22.33
|
|
Blood Biomarkers of Inflammation.
FOXP3 change at Week 24
|
-0.02 pg/ml
Standard Deviation 0.338
|
PRIMARY outcome
Timeframe: 24 WeeksPopulation: A total of nine (9) participants completed both PET scans at Baseline and a follow-up scan after at least 18 weeks of treatment with RNS60 (study drug).
Glial activation was estimated in a subset of participants by magnetic resonance positron emission tomography (MR-PET) using the \[11C\]-PBR28 ligand. The subset excludes individuals homozygous for the T/T allele of the Ala147Thr TSPO polymorphism (rs6971) associated with low affinity for \[11C\]-PBR28. Glial activation was quantified as a mean standardized uptake value (SUV) using PET images acquired 60 to 90 minutes post-injection of approximately 430 MBq \[11C\]-PBR28. FreeSurfer v6.0 (https://surfer.nmr.mgh.harvard.edu) was employed to circumscribe a region of interest (ROI) defined anatomically as the precentral gyrus and the anterior portion of the paracentral lobule, bilaterally. SUV of the ROI was normalized to the SUV of the whole brain and expressed as a SUV ratio (SUVR) to control for inter-individual variability in the global \[11C\]-PBR28 PET signal. Per the protocol, the first treatment was administered on Day 0 (Baseline) and the 24th treatment was administered on Day 161 (
Outcome measures
| Measure |
RNS60
n=9 Participants
RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.
|
|---|---|
|
Change From Baseline in Standardized Uptake Value (SUV) Normalized to Whole Brain Mean (SUVR) at Approximately 60-90 Minutes Post Injection
|
0.02 Ratio
Interval -0.002 to 0.042
|
PRIMARY outcome
Timeframe: 24 WeeksThe vital capacity (VC) (percent of predicted normal) was determined using the slow VC method. Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as the Week 23 minus the Baseline of percent of predicted normal.Per the protocol, the first treatment was administered on Day 0 (Baseline) and the 24th treatment was administered on Day 161 (Week 23).
Outcome measures
| Measure |
RNS60
n=16 Participants
RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.
|
|---|---|
|
Clinical Outcome: Change in Pulmonary Function From Baseline to Week 23, Measured by Slow Vital Capacity (SVC)
|
-3.3 percent predicted max value
Standard Deviation 10.16
|
PRIMARY outcome
Timeframe: 24 WeeksAccurate Test of Limb Isometric Strength (ATLIS) is a non-invasive device that allows measurements of isometric strength in 12 muscle groups of the arms and legs using a standard protocol (elbow and knee flexion and extension, grip, and dorsiflexion). Results are presented as Week 23 minus Baseline of percentages of predicted normal strength based on age, gender, height, and weight using normative data. Per the protocol, the first treatment was administered on Day 0 (Baseline) and the 24th treatment was administered on Day 161 (Week 23).
Outcome measures
| Measure |
RNS60
n=16 Participants
RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.
|
|---|---|
|
Clinical Outcome: Change in Strength From Baseline to Week 23, Measured by Accurate Test of Limb Isometric Strength (ATLIS)
ATLIS Leg Measures
|
-9.1 % predicted normal strength
Standard Deviation 12.91
|
|
Clinical Outcome: Change in Strength From Baseline to Week 23, Measured by Accurate Test of Limb Isometric Strength (ATLIS)
ATLIS Arm Measures
|
-9.0 % predicted normal strength
Standard Deviation 7.19
|
PRIMARY outcome
Timeframe: 24 WeeksThe ALSFRS-R is a quickly administered (5 minute) ordinal rating scale used to determine a subject's assessment of their capability and independence in 12 functional activities. There are 12 questions, graded by the subject 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects change from Baseline to Week 23 in speech and swallowing, fine motor skills, large motor skills, and breathing. Per the protocol, the first treatment was administered on Day 0 (Baseline) and the 24th treatment was administered on Day 161 (Week 23).
Outcome measures
| Measure |
RNS60
n=16 Participants
RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.
|
|---|---|
|
Clinical Outcome: Change in Functional Status Between Baseline and Week 23, Measured by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
|
-5.6 scores on a scale
Standard Deviation 3.96
|
Adverse Events
RNS60
Serious adverse events
| Measure |
RNS60
n=16 participants at risk
RNS60: RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 28 weeks.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
Other adverse events
| Measure |
RNS60
n=16 participants at risk
RNS60: RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 28 weeks.
|
|---|---|
|
Ear and labyrinth disorders
Vertigo
|
6.2%
1/16 • Number of events 2 • 28 weeks
|
|
Eye disorders
Conjunctival Haemorrhage
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Eye disorders
Eye Irritation
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Eye disorders
Vision Blurred
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Gastrointestinal disorders
Constipation
|
18.8%
3/16 • Number of events 6 • 28 weeks
|
|
Gastrointestinal disorders
Defaecation Urgency
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
2/16 • Number of events 4 • 28 weeks
|
|
Gastrointestinal disorders
Flatulence
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Gastrointestinal disorders
Haemorrhoids
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Gastrointestinal disorders
Nausea
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Gastrointestinal disorders
Toothache
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
General disorders
Asthenia
|
6.2%
1/16 • Number of events 2 • 28 weeks
|
|
General disorders
Chest Pain
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
General disorders
Fatigue
|
18.8%
3/16 • Number of events 6 • 28 weeks
|
|
General disorders
Feeling Abnormal
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
General disorders
Feeling Cold
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
General disorders
Feeling hot
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
General disorders
Implant site pain
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
General disorders
Infusion site bruising
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
General disorders
Infusion site discomfort
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
General disorders
Infusion site extravasation
|
12.5%
2/16 • Number of events 2 • 28 weeks
|
|
General disorders
Infusion site pain
|
12.5%
2/16 • Number of events 2 • 28 weeks
|
|
General disorders
Injection site bruising
|
12.5%
2/16 • Number of events 2 • 28 weeks
|
|
General disorders
Injection site extrvasation
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
General disorders
Oedema peripheral
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
General disorders
Pain
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Immune system disorders
Seasonal allergy
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Infections and infestations
Cellulitis
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Infections and infestations
Nasopharyngitis
|
31.2%
5/16 • Number of events 5 • 28 weeks
|
|
Infections and infestations
Sinusitis
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
25.0%
4/16 • Number of events 4 • 28 weeks
|
|
Injury, poisoning and procedural complications
Animal bite
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Injury, poisoning and procedural complications
Contusion
|
25.0%
4/16 • Number of events 7 • 28 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
68.8%
11/16 • Number of events 47 • 28 weeks
|
|
Injury, poisoning and procedural complications
Head injury
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Injury, poisoning and procedural complications
Joint injury
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Injury, poisoning and procedural complications
Laceration
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Injury, poisoning and procedural complications
Overdose
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Injury, poisoning and procedural complications
Post-traumatic pain
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
18.8%
3/16 • Number of events 6 • 28 weeks
|
|
Injury, poisoning and procedural complications
Skin laceration
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Injury, poisoning and procedural complications
Stoma site pain
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Investigations
Alanine aminotransferase increased
|
6.2%
1/16 • Number of events 2 • 28 weeks
|
|
Investigations
Aspartate aminotransferase increased
|
6.2%
1/16 • Number of events 2 • 28 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.2%
1/16 • Number of events 2 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle haemorrhage
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
12.5%
2/16 • Number of events 2 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
6.2%
1/16 • Number of events 2 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.5%
2/16 • Number of events 2 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Nervous system disorders
Balance disorder
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Nervous system disorders
Dizziness
|
12.5%
2/16 • Number of events 2 • 28 weeks
|
|
Nervous system disorders
Headache
|
37.5%
6/16 • Number of events 13 • 28 weeks
|
|
Nervous system disorders
Hypoaesthesia
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Nervous system disorders
Tension headache
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Nervous system disorders
Tremor
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Psychiatric disorders
Insomnia
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Psychiatric disorders
Mood altered
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Renal and urinary disorders
Chromaturia
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Renal and urinary disorders
Urine odour abnormal
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
2/16 • Number of events 2 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
6.2%
1/16 • Number of events 2 • 28 weeks
|
|
Surgical and medical procedures
Skin lesion excision
|
6.2%
1/16 • Number of events 1 • 28 weeks
|
Additional Information
Sabrina Paganoni, MD, PhD
Massachusetts General Hospital
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place