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Open-label Safety Extension Study Assessing Safety and Tolerability of LAI in Patients Who Participated in Study INS-212

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ClinicalTrials.gov Identifier: NCT02628600
Recruitment Status : Completed
First Posted : December 11, 2015
Results First Posted : November 19, 2019
Last Update Posted : February 10, 2020
Sponsor:
Information provided by (Responsible Party):
Insmed Incorporated

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition NTM Lung Infection Due to MAC
Interventions Drug: LAI 590 mg
Drug: Multi-drug regimen
Enrollment 163
Recruitment Details  
Pre-assignment Details Participants in Study INS-212 had either received 590 mg LAI plus an MDR (LAI + MDR arm) or a multidrug regimen alone (MDR alone arm). All participants in this safety extension study, INS-312, were to continue the multidrug antimycobacterial regimen that they were receiving during Study INS-212 and received LAI 590 mg QD for up to 12 months.
Arm/Group Title Prior LAI + Multidrug Regimen Prior Multidrug Regimen Alone
Hide Arm/Group Description Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR. Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR.
Period Title: Overall Study
Started 73 90
Participant Discontinued the Study 24 32
Completed 49 58
Not Completed 24 32
Reason Not Completed
Death             2             1
Adverse Event             3             20
Protocol Violation             0             1
Lack of Efficacy             2             0
Withdrawal by Subject             13             8
Lost to Follow-up             1             0
Physician Decision             2             2
Other not specified             1             0
Arm/Group Title Prior LAI + Multidrug Regimen Prior Multidrug Regimen Alone Total
Hide Arm/Group Description Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR. Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR. Total of all reporting groups
Overall Number of Baseline Participants 73 90 163
Hide Baseline Analysis Population Description
Safety population, defined as participants who received at least 1 dose of LAI.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 73 participants 90 participants 163 participants
64.9  (9.12) 64.8  (10.33) 64.8  (9.78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 73 participants 90 participants 163 participants
Female
51
  69.9%
54
  60.0%
105
  64.4%
Male
22
  30.1%
36
  40.0%
58
  35.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 73 participants 90 participants 163 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
28
  38.4%
22
  24.4%
50
  30.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   2.7%
3
   3.3%
5
   3.1%
White
41
  56.2%
60
  66.7%
101
  62.0%
More than one race
1
   1.4%
0
   0.0%
1
   0.6%
Unknown or Not Reported
1
   1.4%
5
   5.6%
6
   3.7%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description TEAEs are defined as those AEs that occurred on or after the date of first dose of study medication in INS-312 and within 28 days after the last dose. If it couldn't be determined whether the AE is treatment emergent due to a partial onset date, then it was classified as treatment emergent.
Time Frame From baseline to 28 days after end of treatment, up to 13 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Prior LAI + Multidrug Regimen Prior Multidrug Regimen Alone
Hide Arm/Group Description:
Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR.
Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR.
Overall Number of Participants Analyzed 73 90
Measure Type: Number
Unit of Measure: participants
≥1 Treatment-emergent AE (TEAE) 68 90
≥1 Serious TEAE (sTEAE) 20 32
≥1 TEAE leading to study drug withdrawn 8 24
≥1 TE AE Leading to LAI withdrawn 6 22
≥1 TEAE Leading to MDR for NTM withdrawn 4 8
≥1 TEAE Leading to LAI and MDR for NTM withdrawn 1 5
≥1 sTEAE leading to LAI withdrawn 3 9
≥1 TEAE leading to death 2 4
2.Secondary Outcome
Title Number of Participants Achieving Culture Conversion by Month 6 and Month 12
Hide Description

6 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 6 (last opportunity to convert was at Month 4).

12 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 12 (last opportunity to convert was at Month 10).

Time Frame by Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Prior LAI + Multidrug Regimen Prior Multidrug Regimen Alone
Hide Arm/Group Description:
Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR.
Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR.
Overall Number of Participants Analyzed 73 90
Measure Type: Count of Participants
Unit of Measure: Participants
6 months
7
   9.6%
24
  26.7%
12 months
10
  13.7%
30
  33.3%
3.Secondary Outcome
Title Time to Culture Conversion
Hide Description The time to culture conversion is defined as the date of conversion for participants achieving culture conversion is defined as the date of the first of 3-consecutive monthly negative sputum cultures. Then, the number of days to culture conversion is defined as the difference between the date of conversion and the date of first dose of LAI.
Time Frame by Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was the set of all enrolled participants who received at least 1 dose of LAI.
Arm/Group Title Prior LAI + Multidrug Regimen Prior Multidrug Regimen Alone
Hide Arm/Group Description:
Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR.
Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR.
Overall Number of Participants Analyzed 73 90
Median (Full Range)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Not able to be estimated due to an insufficient number of participants achieving conversion
4.Secondary Outcome
Title Change From Baseline (Day 1) to Month 6 and Month 12 in the 6MWT Distance
Hide Description A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and Month 6 and Month 12/EOT. The standardized protocol based on the American Thoracic Society (ATS) guidelines (http://doi.org/10.1164/ajrccm.166.1.at1102) was used. After assessments were performed for heart rate, blood pressure, pulse oximetry (SpO2), dyspnea, and overall fatigue using the Borg scale, participants were instructed to walk on a prescribed course as far as they could in 6 minutes. Pre-test assessment parameters were repeated after exertion. The maximum distance achieved and post exertion heart rate and SpO2 were compared to pre-test values. The maximum distance achieved was recorded in the electronic case report form.
Time Frame From baseline to Month 12 or end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description

Baseline: number of participants with data at this visit.

Change from baseline: number of participants with both baseline and 6 month scores.

Arm/Group Title Prior LAI + Multidrug Regimen Prior Multidrug Regimen Alone
Hide Arm/Group Description:
Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR.
Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR.
Overall Number of Participants Analyzed 73 90
Mean (Standard Deviation)
Unit of Measure: meters
Baseline Number Analyzed 58 participants 71 participants
435.9  (132.33) 449.0  (122.64)
Change from Baseline to Month 6 Number Analyzed 58 participants 71 participants
-10.4  (69.77) -20.8  (51.57)
Change from Baseline to Month 12 Number Analyzed 47 participants 56 participants
-10.1  (79.23) -42.2  (72.66)
Time Frame From baseline up to 28 days after end of treatment, up to 13 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Prior LAI + Multidrug Regimen Prior Multidrug Regimen Alone
Hide Arm/Group Description Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR. Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR.
All-Cause Mortality
Prior LAI + Multidrug Regimen Prior Multidrug Regimen Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   2/73 (2.74%)      4/90 (4.44%)    
Hide Serious Adverse Events
Prior LAI + Multidrug Regimen Prior Multidrug Regimen Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/73 (27.40%)      32/90 (35.56%)    
Cardiac disorders     
Atrial fibrillation  1  1/73 (1.37%)  2/90 (2.22%) 
Eye disorders     
Cataract  1  2/73 (2.74%)  0/90 (0.00%) 
Vision blurred  1  0/73 (0.00%)  1/90 (1.11%) 
Gastrointestinal disorders     
Ascites  1  0/73 (0.00%)  1/90 (1.11%) 
Gastritis  1  0/73 (0.00%)  1/90 (1.11%) 
General disorders     
Asthenia  1  1/73 (1.37%)  0/90 (0.00%) 
Chest pain  1  1/73 (1.37%)  0/90 (0.00%) 
Performance status decreased  1  0/73 (0.00%)  1/90 (1.11%) 
Infections and infestations     
Bronchopulmonary aspergillosis allergic  1  0/73 (0.00%)  1/90 (1.11%) 
Gastroenteritis viral  1  1/73 (1.37%)  0/90 (0.00%) 
Infective exacerbation of bronchiectasis  1  1/73 (1.37%)  3/90 (3.33%) 
Laryngitis  1  0/73 (0.00%)  1/90 (1.11%) 
Lower respiratory tract infection  1  1/73 (1.37%)  0/90 (0.00%) 
Mycobacterium abscessus infection  1  1/73 (1.37%)  0/90 (0.00%) 
Mycobacterium avium complex infection  1  2/73 (2.74%)  5/90 (5.56%) 
Pneumonia  1  3/73 (4.11%)  4/90 (4.44%) 
Pneumonia fungal  1  0/73 (0.00%)  1/90 (1.11%) 
Post procedural pneumonia  1  0/73 (0.00%)  1/90 (1.11%) 
Respiratory tract infection  1  1/73 (1.37%)  0/90 (0.00%) 
Sinobronchitis  1  0/73 (0.00%)  1/90 (1.11%) 
Injury, poisoning and procedural complications     
Hip fracture  1  2/73 (2.74%)  0/90 (0.00%) 
Pelvic fracture  1  0/73 (0.00%)  1/90 (1.11%) 
Radius fracture  1  1/73 (1.37%)  0/90 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  1/73 (1.37%)  0/90 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/73 (1.37%)  0/90 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer  1  0/73 (0.00%)  1/90 (1.11%) 
Nervous system disorders     
Cerebral infarction  1  0/73 (0.00%)  1/90 (1.11%) 
Neuropathy peripheral  1  0/73 (0.00%)  1/90 (1.11%) 
Transient ischaemic attack  1  1/73 (1.37%)  0/90 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/73 (0.00%)  1/90 (1.11%) 
Alveolitis allergic  1  1/73 (1.37%)  0/90 (0.00%) 
Chronic obstructive pulmonary disease  1  2/73 (2.74%)  4/90 (4.44%) 
Dyspnoea  1  0/73 (0.00%)  1/90 (1.11%) 
Dyspnoea at rest  1  0/73 (0.00%)  1/90 (1.11%) 
Haemoptysis  1  1/73 (1.37%)  2/90 (2.22%) 
Hypoxia  1  0/73 (0.00%)  1/90 (1.11%) 
Interstitial lung disease  1  0/73 (0.00%)  1/90 (1.11%) 
Lung infiltration  1  0/73 (0.00%)  1/90 (1.11%) 
Pneumothorax  1  0/73 (0.00%)  2/90 (2.22%) 
Pulmonary embolism  1  0/73 (0.00%)  2/90 (2.22%) 
Pulmonary fibrosis  1  0/73 (0.00%)  1/90 (1.11%) 
Respiratory failure  1  0/73 (0.00%)  2/90 (2.22%) 
1
Term from vocabulary, MedDRA version 17.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Prior LAI + Multidrug Regimen Prior Multidrug Regimen Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/73 (61.64%)      75/90 (83.33%)    
Gastrointestinal disorders     
Diarrhoea  1  4/73 (5.48%)  5 9/90 (10.00%)  11
Nausea  1  5/73 (6.85%)  6 9/90 (10.00%)  10
General disorders     
Fatigue  1  3/73 (4.11%)  3 13/90 (14.44%)  13
Infections and infestations     
Nasopharyngitis  1  10/73 (13.70%)  11 7/90 (7.78%)  10
Infective exacerbation of bronchiectasis  1  6/73 (8.22%)  7 10/90 (11.11%)  10
Investigations     
Weight decreased  1  7/73 (9.59%)  7 8/90 (8.89%)  8
Renal and urinary disorders     
Haematuria  1  4/73 (5.48%)  4 5/90 (5.56%)  6
Respiratory, thoracic and mediastinal disorders     
Dysphonia  1  5/73 (6.85%)  6 39/90 (43.33%)  54
Cough  1  9/73 (12.33%)  10 32/90 (35.56%)  37
Dyspnoea  1  9/73 (12.33%)  10 16/90 (17.78%)  17
Haemoptysis  1  10/73 (13.70%)  10 9/90 (10.00%)  10
Productive cough  1  4/73 (5.48%)  5 6/90 (6.67%)  6
Oropharyngeal pain  1  2/73 (2.74%)  2 7/90 (7.78%)  8
1
Term from vocabulary, MedDRA version 17.1
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.
The PI agrees 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 Vice President, Clinical Development & Medical Affairs, ALIS)
Organization: Insmed Inc
Phone: 908-947-2651
EMail: kevin.mange@insmed.com
Layout table for additonal information
Responsible Party: Insmed Incorporated
ClinicalTrials.gov Identifier: NCT02628600    
Other Study ID Numbers: INS-312
2015-003170-33 ( EudraCT Number )
First Submitted: December 8, 2015
First Posted: December 11, 2015
Results First Submitted: October 15, 2019
Results First Posted: November 19, 2019
Last Update Posted: February 10, 2020