Trial Outcomes & Findings for Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKAYCE™) - Extension Phase (NCT NCT03905642)
NCT ID: NCT03905642
Last Updated: 2020-07-30
Results Overview
Number of Participants with indicated Adverse Events in subjects receiving 560 mg once daily dose of Arikayce™ administered for 6 cycles over 18 months.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
49 participants
Primary outcome timeframe
18 Months
Results posted on
2020-07-30
Participant Flow
Participant milestones
| Measure |
560 mg Arikayce™
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
Overall Study
STARTED
|
49
|
|
Overall Study
COMPLETED
|
41
|
|
Overall Study
NOT COMPLETED
|
8
|
Reasons for withdrawal
| Measure |
560 mg Arikayce™
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Pregnancy
|
1
|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
|
Overall Study
Completed study but not 24 of 28 days
|
2
|
Baseline Characteristics
Safety population
Baseline characteristics by cohort
| Measure |
560 mg Arikayce™
n=49 Participants
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
Age, Continuous
|
17.4 years
STANDARD_DEVIATION 6.22 • n=49 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=49 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=49 Participants
|
|
FEV1 % predicted
|
59.73 Percent %
STANDARD_DEVIATION 20.047 • n=49 Participants
|
|
P. aeruginosa density
|
6.289 Log10 CFU/mL
STANDARD_DEVIATION 2.8587 • n=44 Participants • Safety population
|
PRIMARY outcome
Timeframe: 18 MonthsNumber of Participants with indicated Adverse Events in subjects receiving 560 mg once daily dose of Arikayce™ administered for 6 cycles over 18 months.
Outcome measures
| Measure |
560 mg Arikayce™
n=49 Participants
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Any Adverse Event
|
48 participants
|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Treatment-related adverse events
|
15 participants
|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Grade 1: Mild
|
28 participants
|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Grade 2: Moderate
|
15 participants
|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Grade 3: Severe
|
4 participants
|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Grade 4: Life-threatening or disabling
|
1 participants
|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Grade 5: Death
|
0 participants
|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Serious Adverse Events
|
15 participants
|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Treatment-related serious adverse events
|
0 participants
|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Deaths
|
0 participants
|
|
Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Permanent discontinuations due to adverse events
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline, Days1, 14, 28, 56, 70, 85, 98, 112, 140, 154, 169, 182,196, 224, 238, 253, 266, 280, 308, 322, 337, 350, 364, 392, 406, 421, 434, 448, 476, 490, and 504Population: Safety population
A summary of relative change from extension study baseline time points in FEV1 % predicted is presented for the overall safety population and by treatment received.
Outcome measures
| Measure |
560 mg Arikayce™
n=49 Participants
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
FEV1 % Predicted
Day 1
|
3.13 Percent (%) predicted
Standard Deviation 8.553
|
|
FEV1 % Predicted
Day 14
|
7.62 Percent (%) predicted
Standard Deviation 15.246
|
|
FEV1 % Predicted
Baseline
|
59.73 Percent (%) predicted
Standard Deviation 20.047
|
|
FEV1 % Predicted
Day 28
|
6.83 Percent (%) predicted
Standard Deviation 14.593
|
|
FEV1 % Predicted
Day 56
|
3.02 Percent (%) predicted
Standard Deviation 11.174
|
|
FEV1 % Predicted
Day 70
|
2.96 Percent (%) predicted
Standard Deviation 13.580
|
|
FEV1 % Predicted
Day 85
|
4.04 Percent (%) predicted
Standard Deviation 15.450
|
|
FEV1 % Predicted
Day 98
|
9.97 Percent (%) predicted
Standard Deviation 16.594
|
|
FEV1 % Predicted
Day 112
|
8.19 Percent (%) predicted
Standard Deviation 20.116
|
|
FEV1 % Predicted
Day 140
|
4.86 Percent (%) predicted
Standard Deviation 19.337
|
|
FEV1 % Predicted
Day 154
|
6.76 Percent (%) predicted
Standard Deviation 20.633
|
|
FEV1 % Predicted
Day 169
|
3.90 Percent (%) predicted
Standard Deviation 19.141
|
|
FEV1 % Predicted
Day 182
|
10.22 Percent (%) predicted
Standard Deviation 18.349
|
|
FEV1 % Predicted
Day 196
|
7.56 Percent (%) predicted
Standard Deviation 20.607
|
|
FEV1 % Predicted
Day 224
|
2.57 Percent (%) predicted
Standard Deviation 19.165
|
|
FEV1 % Predicted
Day 238
|
5.46 Percent (%) predicted
Standard Deviation 17.872
|
|
FEV1 % Predicted
Day 253
|
3.37 Percent (%) predicted
Standard Deviation 17.755
|
|
FEV1 % Predicted
Day 266
|
9.07 Percent (%) predicted
Standard Deviation 19.747
|
|
FEV1 % Predicted
Day 280
|
8.54 Percent (%) predicted
Standard Deviation 19.179
|
|
FEV1 % Predicted
Day 308
|
5.77 Percent (%) predicted
Standard Deviation 19.633
|
|
FEV1 % Predicted
Day 322
|
5.25 Percent (%) predicted
Standard Deviation 20.946
|
|
FEV1 % Predicted
Day 337
|
5.18 Percent (%) predicted
Standard Deviation 21.740
|
|
FEV1 % Predicted
Day 350
|
10.49 Percent (%) predicted
Standard Deviation 21.615
|
|
FEV1 % Predicted
Day 364
|
3.82 Percent (%) predicted
Standard Deviation 18.895
|
|
FEV1 % Predicted
Day 392
|
3.07 Percent (%) predicted
Standard Deviation 18.380
|
|
FEV1 % Predicted
Day 406
|
2.74 Percent (%) predicted
Standard Deviation 18.301
|
|
FEV1 % Predicted
Day 421
|
1.63 Percent (%) predicted
Standard Deviation 19.094
|
|
FEV1 % Predicted
Day 434
|
7.11 Percent (%) predicted
Standard Deviation 20.022
|
|
FEV1 % Predicted
Day 448
|
5.66 Percent (%) predicted
Standard Deviation 20.422
|
|
FEV1 % Predicted
Day 476
|
0.83 Percent (%) predicted
Standard Deviation 21.741
|
|
FEV1 % Predicted
Day 490
|
1.61 Percent (%) predicted
Standard Deviation 19.922
|
|
FEV1 % Predicted
Day 504
|
0.06 Percent (%) predicted
Standard Deviation 22.196
|
SECONDARY outcome
Timeframe: Baseline, Days 14, 28, 85, 98, 112, 140, 169, 182,196, 253, 266, 280, 337, 350, 364, 421, 434, and 448Population: Per Protocol population defined as all patients who completed at least 24 of the 28 days of dosing for each of the 6 cycles
A summary of change from extension study baseline to all post-baseline time points during the treatment periods and at the end of the off-treatment periods in P aeruginosa sputum density (log10 CFU/mL) is presented for the overall safety population and by treatment received.
Outcome measures
| Measure |
560 mg Arikayce™
n=49 Participants
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
Absolute Change in Sputum Density
Baseline
|
6.289 Log 10 CFU/mL
Standard Deviation 2.8587
|
|
Absolute Change in Sputum Density
Day 14
|
-1.196 Log 10 CFU/mL
Standard Deviation 2.0736
|
|
Absolute Change in Sputum Density
Day 28
|
-0.416 Log 10 CFU/mL
Standard Deviation 1.8584
|
|
Absolute Change in Sputum Density
Day 85
|
0.154 Log 10 CFU/mL
Standard Deviation 2.4433
|
|
Absolute Change in Sputum Density
Day 98
|
-0.623 Log 10 CFU/mL
Standard Deviation 1.9127
|
|
Absolute Change in Sputum Density
Day 112
|
-0.781 Log 10 CFU/mL
Standard Deviation 1.1625
|
|
Absolute Change in Sputum Density
Day 140
|
-0.266 Log 10 CFU/mL
Standard Deviation 0.2871
|
|
Absolute Change in Sputum Density
Day 169
|
-0.144 Log 10 CFU/mL
Standard Deviation 1.2470
|
|
Absolute Change in Sputum Density
Day 182
|
-1.087 Log 10 CFU/mL
Standard Deviation 1.9582
|
|
Absolute Change in Sputum Density
Day 196
|
-0.599 Log 10 CFU/mL
Standard Deviation 1.3450
|
|
Absolute Change in Sputum Density
Day 253
|
0.213 Log 10 CFU/mL
Standard Deviation 1.4059
|
|
Absolute Change in Sputum Density
Day 266
|
-0.991 Log 10 CFU/mL
Standard Deviation 2.5040
|
|
Absolute Change in Sputum Density
Day 280
|
-0.702 Log 10 CFU/mL
Standard Deviation 1.7419
|
|
Absolute Change in Sputum Density
Day 337
|
0.375 Log 10 CFU/mL
Standard Deviation 1.9924
|
|
Absolute Change in Sputum Density
Day 350
|
-0.311 Log 10 CFU/mL
Standard Deviation 1.6342
|
|
Absolute Change in Sputum Density
Day 364
|
-0.107 Log 10 CFU/mL
Standard Deviation 1.8027
|
|
Absolute Change in Sputum Density
Day 421
|
0.494 Log 10 CFU/mL
Standard Deviation 2.0058
|
|
Absolute Change in Sputum Density
Day 434
|
0.111 Log 10 CFU/mL
Standard Deviation 1.9098
|
|
Absolute Change in Sputum Density
Day 448
|
0.034 Log 10 CFU/mL
Standard Deviation 2.0020
|
SECONDARY outcome
Timeframe: 18 MonthsThe duration of IV and all systemic or inhaled antipseudomonal rescue therapy is presented for the overall safety population and by treatment received.
Outcome measures
| Measure |
560 mg Arikayce™
n=49 Participants
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
Antipseudomonal Rescue Therapy - Duration of Therapy
|
39.7 days
Standard Deviation 44.57
|
SECONDARY outcome
Timeframe: 18 MonthsThe time to IV and all systemic or inhaled antipseudomonal rescue therapy is presented for the overall safety population and by treatment received.
Outcome measures
| Measure |
560 mg Arikayce™
n=49 Participants
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
Antipseudomonal Rescue Therapy - Time to Therapy
By Day 85
|
2.0 percentage % participants
|
|
Antipseudomonal Rescue Therapy - Time to Therapy
By Day 253
|
17.2 percentage % participants
|
|
Antipseudomonal Rescue Therapy - Time to Therapy
By Day 504
|
32.9 percentage % participants
|
SECONDARY outcome
Timeframe: Days 14, 28, 85, 98, 112, 169, 182,196, 253, 266, 280, 337, 350, 364, 421, 434, and 448Population: Per Protocol population defined as all patients who completed at least 24 of the 28 days of dosing for each of the 6 cycles
A summary of absolute change from baseline in the CFQ-R scales at each on-treatment assessment between Day 14 and Day 448 is presented for all patients and by main study treatment group for the safety population. CFQ-R is a disease specific instrument designed to measure impact on overall health, daily life, perceived well-being and symptoms on a scale from 0 to 100 points. Higher values represent a more favorable outcome.
Outcome measures
| Measure |
560 mg Arikayce™
n=49 Participants
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 266
|
10.041 percentage %
Standard Deviation 14.5240
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 14
|
7.616 percentage %
Standard Deviation 14.1662
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 28
|
11.486 percentage %
Standard Deviation 14.9347
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 85
|
9.697 percentage %
Standard Deviation 12.9834
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 98
|
11.235 percentage %
Standard Deviation 14.5552
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 112
|
11.768 percentage %
Standard Deviation 13.9321
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 169
|
5.159 percentage %
Standard Deviation 13.6851
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 182
|
9.233 percentage %
Standard Deviation 16.3635
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 196
|
9.404 percentage %
Standard Deviation 12.4334
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 253
|
7.097 percentage %
Standard Deviation 13.7509
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 280
|
6.111 percentage %
Standard Deviation 11.3611
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 337
|
9.017 percentage %
Standard Deviation 13.8786
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 350
|
12.108 percentage %
Standard Deviation 13.8668
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 364
|
11.875 percentage %
Standard Deviation 12.9679
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 421
|
11.895 percentage %
Standard Deviation 14.1632
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 434
|
13.718 percentage %
Standard Deviation 13.1377
|
|
Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Day 448
|
13.120 percentage %
Standard Deviation 14.0144
|
Adverse Events
560 mg Arikayce™
Serious events: 15 serious events
Other events: 29 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
560 mg Arikayce™
n=49 participants at risk
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
Congenital, familial and genetic disorders
Cystic fibrosis lung
|
22.4%
11/49 • Number of events 17 • 18 months
|
|
Infections and infestations
Endocarditis
|
2.0%
1/49 • Number of events 2 • 18 months
|
|
Infections and infestations
Appendicitis
|
2.0%
1/49 • Number of events 1 • 18 months
|
|
Infections and infestations
Bronchitis
|
2.0%
1/49 • Number of events 1 • 18 months
|
|
Infections and infestations
Influenza
|
2.0%
1/49 • Number of events 1 • 18 months
|
|
Investigations
Endoscopy
|
2.0%
1/49 • Number of events 1 • 18 months
|
|
Psychiatric disorders
Drug abuse
|
2.0%
1/49 • Number of events 1 • 18 months
|
|
Reproductive system and breast disorders
Testicular appendage torsion
|
2.0%
1/49 • Number of events 1 • 18 months
|
|
Surgical and medical procedures
Drug therapy
|
2.0%
1/49 • Number of events 1 • 18 months
|
Other adverse events
| Measure |
560 mg Arikayce™
n=49 participants at risk
Subjects in this cohort will receive 560 mg of Arikayce™
Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.
|
|---|---|
|
Infections and infestations
Nasopharyngitis
|
28.6%
14/49 • Number of events 26 • 18 months
|
|
Infections and infestations
Rhinitis
|
22.4%
11/49 • Number of events 19 • 18 months
|
|
Infections and infestations
Influenza
|
12.2%
6/49 • Number of events 7 • 18 months
|
|
Infections and infestations
Respiratory tract infection viral
|
10.2%
5/49 • Number of events 12 • 18 months
|
|
Infections and infestations
Pharyngitis
|
10.2%
5/49 • Number of events 5 • 18 months
|
|
Infections and infestations
Sinusitis
|
8.2%
4/49 • Number of events 4 • 18 months
|
|
Infections and infestations
Bronchitis
|
6.1%
3/49 • Number of events 6 • 18 months
|
|
Infections and infestations
Viral rhinitis
|
6.1%
3/49 • Number of events 4 • 18 months
|
|
Infections and infestations
Viral infection
|
6.1%
3/49 • Number of events 3 • 18 months
|
|
Congenital, familial and genetic disorders
Cystic fibrosis lung
|
49.0%
24/49 • Number of events 67 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
28.6%
14/49 • Number of events 33 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Haemopytsis
|
24.5%
12/49 • Number of events 20 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
22.4%
11/49 • Number of events 14 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
14.3%
7/49 • Number of events 13 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.2%
5/49 • Number of events 6 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
8.2%
4/49 • Number of events 4 • 18 months
|
|
Gastrointestinal disorders
Abdominal Pain
|
8.2%
4/49 • Number of events 5 • 18 months
|
|
Gastrointestinal disorders
Abdominal Pain upper
|
6.1%
3/49 • Number of events 4 • 18 months
|
|
General disorders
Pyrexia
|
10.2%
5/49 • Number of events 7 • 18 months
|
|
Investigations
Blood alkaline phosphatase increased
|
6.1%
3/49 • Number of events 4 • 18 months
|
|
Nervous system disorders
Headache
|
6.1%
3/49 • Number of events 3 • 18 months
|
Additional Information
Kevin Mange (Senior VP, Clinical Development and Medical Affairs)
Insmed Incorporated
Phone: 908-947-2651
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Per the signed Investigator Agreement in the study protocol and protocol amendments, the PI agreed "not to originate or use the name of Insmed Incorporated, or study drug code in any publicity, news release, or other public announcement, written or oral, whether to the public, press, or otherwise, relating to this protocol, to any amendment to the protocol, or to the performance of this protocol, without the prior written consent of Insmed Incorporated."
- Publication restrictions are in place
Restriction type: OTHER