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Study of Dose Escalation of Liposomal Amikacin for Inhalation (ARIKAYCE™) - Extension Phase

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ClinicalTrials.gov Identifier: NCT03905642
Recruitment Status : Completed
First Posted : April 5, 2019
Results First Posted : May 14, 2019
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
Insmed Incorporated

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Intervention Drug: Arikayce™
Enrollment 49
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 560 mg Arikayce™
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Subjects in this cohort will receive 560 mg of Arikayce™

Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.

Period Title: Overall Study
Started 49
Completed 41
Not Completed 8
Reason Not Completed
Withdrawal by Subject             3
Pregnancy             1
Adverse Event             1
Lack of Efficacy             1
Completed study but not 24 of 28 days             2
Arm/Group Title 560 mg Arikayce™
Hide Arm/Group Description

Subjects in this cohort will receive 560 mg of Arikayce™

Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.

Overall Number of Baseline Participants 49
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 49 participants
17.4  (6.22)
[1]
Measure Description: Age, 8-31 years
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 49 participants
Female
29
  59.2%
Male
20
  40.8%
FEV1 % predicted  
Mean (Standard Deviation)
Unit of measure:  Percent %
Number Analyzed 49 participants
59.73  (20.047)
P. aeruginosa density   [1] 
Mean (Standard Deviation)
Unit of measure:  Log10 CFU/mL
Number Analyzed 44 participants
6.289  (2.8587)
[1]
Measure Analysis Population Description: Safety population
1.Primary Outcome
Title Adverse Event Profile of 560 mg Once Daily Dose of Arikayce™ Administered for Six Cycles Over Eighteen Months.
Hide Description Number of Participants with indicated Adverse Events in subjects receiving 560 mg once daily dose of Arikayce™ administered for 6 cycles over 18 months.
Time Frame 18 Months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 560 mg Arikayce™
Hide Arm/Group Description:

Subjects in this cohort will receive 560 mg of Arikayce™

Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.

Overall Number of Participants Analyzed 49
Measure Type: Number
Unit of Measure: participants
Any Adverse Event 48
Treatment-related adverse events 15
Grade 1: Mild 28
Grade 2: Moderate 15
Grade 3: Severe 4
Grade 4: Life-threatening or disabling 1
Grade 5: Death 0
Serious Adverse Events 15
Treatment-related serious adverse events 0
Deaths 0
Permanent discontinuations due to adverse events 1
2.Secondary Outcome
Title FEV1 % Predicted
Hide Description 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.
Time Frame 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 504
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Hide Analysis Population Description
Safety population
Arm/Group Title 560 mg Arikayce™
Hide Arm/Group Description:

Subjects in this cohort will receive 560 mg of Arikayce™

Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.

Overall Number of Participants Analyzed 49
Mean (Standard Deviation)
Unit of Measure: Percent (%) predicted
Baseline Number Analyzed 49 participants
59.73  (20.047)
Day 1 Number Analyzed 47 participants
3.13  (8.553)
Day 14 Number Analyzed 46 participants
7.62  (15.246)
Day 28 Number Analyzed 46 participants
6.83  (14.593)
Day 56 Number Analyzed 47 participants
3.02  (11.174)
Day 70 Number Analyzed 48 participants
2.96  (13.580)
Day 85 Number Analyzed 48 participants
4.04  (15.450)
Day 98 Number Analyzed 48 participants
9.97  (16.594)
Day 112 Number Analyzed 48 participants
8.19  (20.116)
Day 140 Number Analyzed 47 participants
4.86  (19.337)
Day 154 Number Analyzed 47 participants
6.76  (20.633)
Day 169 Number Analyzed 46 participants
3.90  (19.141)
Day 182 Number Analyzed 46 participants
10.22  (18.349)
Day 196 Number Analyzed 46 participants
7.56  (20.607)
Day 224 Number Analyzed 46 participants
2.57  (19.165)
Day 238 Number Analyzed 45 participants
5.46  (17.872)
Day 253 Number Analyzed 45 participants
3.37  (17.755)
Day 266 Number Analyzed 45 participants
9.07  (19.747)
Day 280 Number Analyzed 45 participants
8.54  (19.179)
Day 308 Number Analyzed 46 participants
5.77  (19.633)
Day 322 Number Analyzed 45 participants
5.25  (20.946)
Day 337 Number Analyzed 44 participants
5.18  (21.740)
Day 350 Number Analyzed 44 participants
10.49  (21.615)
Day 364 Number Analyzed 44 participants
3.82  (18.895)
Day 392 Number Analyzed 43 participants
3.07  (18.380)
Day 406 Number Analyzed 43 participants
2.74  (18.301)
Day 421 Number Analyzed 43 participants
1.63  (19.094)
Day 434 Number Analyzed 43 participants
7.11  (20.022)
Day 448 Number Analyzed 43 participants
5.66  (20.422)
Day 476 Number Analyzed 43 participants
0.83  (21.741)
Day 490 Number Analyzed 43 participants
1.61  (19.922)
Day 504 Number Analyzed 42 participants
0.06  (22.196)
3.Secondary Outcome
Title Absolute Change in Sputum Density
Hide Description 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.
Time Frame Baseline, Days 14, 28, 85, 98, 112, 140, 169, 182,196, 253, 266, 280, 337, 350, 364, 421, 434, and 448
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Hide Analysis Population Description
Per Protocol population defined as all patients who completed at least 24 of the 28 days of dosing for each of the 6 cycles
Arm/Group Title 560 mg Arikayce™
Hide Arm/Group Description:

Subjects in this cohort will receive 560 mg of Arikayce™

Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.

Overall Number of Participants Analyzed 49
Mean (Standard Deviation)
Unit of Measure: Log 10 CFU/mL
Baseline Number Analyzed 49 participants
6.289  (2.8587)
Day 14 Number Analyzed 37 participants
-1.196  (2.0736)
Day 28 Number Analyzed 43 participants
-0.416  (1.8584)
Day 85 Number Analyzed 40 participants
0.154  (2.4433)
Day 98 Number Analyzed 39 participants
-0.623  (1.9127)
Day 112 Number Analyzed 38 participants
-0.781  (1.1625)
Day 140 Number Analyzed 2 participants
-0.266  (0.2871)
Day 169 Number Analyzed 33 participants
-0.144  (1.2470)
Day 182 Number Analyzed 30 participants
-1.087  (1.9582)
Day 196 Number Analyzed 31 participants
-0.599  (1.3450)
Day 253 Number Analyzed 31 participants
0.213  (1.4059)
Day 266 Number Analyzed 33 participants
-0.991  (2.5040)
Day 280 Number Analyzed 33 participants
-0.702  (1.7419)
Day 337 Number Analyzed 35 participants
0.375  (1.9924)
Day 350 Number Analyzed 36 participants
-0.311  (1.6342)
Day 364 Number Analyzed 37 participants
-0.107  (1.8027)
Day 421 Number Analyzed 34 participants
0.494  (2.0058)
Day 434 Number Analyzed 34 participants
0.111  (1.9098)
Day 448 Number Analyzed 34 participants
0.034  (2.0020)
4.Secondary Outcome
Title Antipseudomonal Rescue Therapy - Duration of Therapy
Hide Description The duration of IV and all systemic or inhaled antipseudomonal rescue therapy is presented for the overall safety population and by treatment received.
Time Frame 18 Months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 560 mg Arikayce™
Hide Arm/Group Description:

Subjects in this cohort will receive 560 mg of Arikayce™

Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.

Overall Number of Participants Analyzed 49
Mean (Standard Deviation)
Unit of Measure: days
39.7  (44.57)
5.Secondary Outcome
Title Antipseudomonal Rescue Therapy - Time to Therapy
Hide Description The time to IV and all systemic or inhaled antipseudomonal rescue therapy is presented for the overall safety population and by treatment received.
Time Frame 18 Months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 560 mg Arikayce™
Hide Arm/Group Description:

Subjects in this cohort will receive 560 mg of Arikayce™

Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.

Overall Number of Participants Analyzed 49
Measure Type: Number
Unit of Measure: percentage % participants
By Day 85 2.0
By Day 253 17.2
By Day 504 32.9
6.Secondary Outcome
Title Analysis of Cystic Fibrosis Questionnaire - Revised (CFQ-R) for Absolute Change in Score
Hide Description 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.
Time Frame Days 14, 28, 85, 98, 112, 169, 182,196, 253, 266, 280, 337, 350, 364, 421, 434, and 448
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Hide Analysis Population Description
Per Protocol population defined as all patients who completed at least 24 of the 28 days of dosing for each of the 6 cycles
Arm/Group Title 560 mg Arikayce™
Hide Arm/Group Description:

Subjects in this cohort will receive 560 mg of Arikayce™

Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.

Overall Number of Participants Analyzed 49
Mean (Standard Deviation)
Unit of Measure: percentage %
Day 14 Number Analyzed 48 participants
7.616  (14.1662)
Day 28 Number Analyzed 46 participants
11.486  (14.9347)
Day 85 Number Analyzed 44 participants
9.697  (12.9834)
Day 98 Number Analyzed 45 participants
11.235  (14.5552)
Day 112 Number Analyzed 44 participants
11.768  (13.9321)
Day 169 Number Analyzed 42 participants
5.159  (13.6851)
Day 182 Number Analyzed 42 participants
9.233  (16.3635)
Day 196 Number Analyzed 41 participants
9.404  (12.4334)
Day 253 Number Analyzed 40 participants
7.097  (13.7509)
Day 266 Number Analyzed 41 participants
10.041  (14.5240)
Day 280 Number Analyzed 40 participants
6.111  (11.3611)
Day 337 Number Analyzed 39 participants
9.017  (13.8786)
Day 350 Number Analyzed 39 participants
12.108  (13.8668)
Day 364 Number Analyzed 40 participants
11.875  (12.9679)
Day 421 Number Analyzed 39 participants
11.895  (14.1632)
Day 434 Number Analyzed 39 participants
13.718  (13.1377)
Day 448 Number Analyzed 39 participants
13.120  (14.0144)
Time Frame 18 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 560 mg Arikayce™
Hide Arm/Group Description

Subjects in this cohort will receive 560 mg of Arikayce™

Arikayce™: Amikacin (aminoglycoside) in a liposomal formulation.

All-Cause Mortality
560 mg Arikayce™
Affected / at Risk (%)
Total   0/49 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
560 mg Arikayce™
Affected / at Risk (%) # Events
Total   15/49 (30.61%)    
Congenital, familial and genetic disorders   
Cystic fibrosis lung   11/49 (22.45%)  17
Infections and infestations   
Endocarditis   1/49 (2.04%)  2
Appendicitis   1/49 (2.04%)  1
Bronchitis   1/49 (2.04%)  1
Influenza   1/49 (2.04%)  1
Investigations   
Endoscopy   1/49 (2.04%)  1
Psychiatric disorders   
Drug abuse   1/49 (2.04%)  1
Reproductive system and breast disorders   
Testicular appendage torsion   1/49 (2.04%)  1
Surgical and medical procedures   
Drug therapy   1/49 (2.04%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
560 mg Arikayce™
Affected / at Risk (%) # Events
Total   41/49 (83.67%)    
Congenital, familial and genetic disorders   
Cystic fibrosis lung   24/49 (48.98%)  67
Gastrointestinal disorders   
Abdominal Pain   4/49 (8.16%)  5
Abdominal Pain upper   3/49 (6.12%)  4
General disorders   
Pyrexia   5/49 (10.20%)  7
Infections and infestations   
Nasopharyngitis   14/49 (28.57%)  26
Rhinitis   11/49 (22.45%)  19
Influenza   6/49 (12.24%)  7
Respiratory tract infection viral   5/49 (10.20%)  12
Pharyngitis   5/49 (10.20%)  5
Sinusitis   4/49 (8.16%)  4
Bronchitis   3/49 (6.12%)  6
Viral rhinitis   3/49 (6.12%)  4
Viral infection   3/49 (6.12%)  3
Investigations   
Blood alkaline phosphatase increased   3/49 (6.12%)  4
Nervous system disorders   
Headache   3/49 (6.12%)  3
Respiratory, thoracic and mediastinal disorders   
Cough   14/49 (28.57%)  33
Haemopytsis   12/49 (24.49%)  20
Productive cough   11/49 (22.45%)  14
Dysphonia   7/49 (14.29%)  13
Oropharyngeal pain   5/49 (10.20%)  6
Throat irritation   4/49 (8.16%)  4
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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."
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Kevin Mange (Senior VP, Clinical Development and Medical Affairs)
Organization: Insmed Incorporated
Phone: 908-947-2651
EMail: kevin.mange@insmed.com
Layout table for additonal information
Responsible Party: Insmed Incorporated
ClinicalTrials.gov Identifier: NCT03905642     History of Changes
Other Study ID Numbers: TR02-105 Extension
First Submitted: April 2, 2019
First Posted: April 5, 2019
Results First Submitted: April 24, 2019
Results First Posted: May 14, 2019
Last Update Posted: June 14, 2019