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Natalizumab De-escalation With Interferon Beta-1b

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ClinicalTrials.gov Identifier: NCT01144052
Recruitment Status : Completed
First Posted : June 15, 2010
Results First Posted : April 17, 2014
Last Update Posted : April 17, 2014
Sponsor:
Collaborator:
Ospedale Civico, Lugano
Information provided by (Responsible Party):
Claudio Gobbi, Ospedale Civico, Lugano

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Relapsing-remitting Multiple Sclerosis
Interventions Drug: interferon beta-1b
Drug: Natalizumab
Enrollment 19
Recruitment Details Recruitment period: 2010 to 2011 Out-patients of Neurology ambulatory
Pre-assignment Details  
Arm/Group Title Natalizumab Interferon-beta-1b
Hide Arm/Group Description Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers’ instructions. 250 mcg (8 MIU) subcutaneous injections every other day
Period Title: Overall Study
Started 10 9
Completed 9 8
Not Completed 1 1
Reason Not Completed
Withdrawal by Subject             1             1
Arm/Group Title Natalizumab Interferon-beta-1b Total
Hide Arm/Group Description Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers’ instructions. 250 mcg (8 MIU) subcutaneous injections every other day Total of all reporting groups
Overall Number of Baseline Participants 10 9 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 19 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
10
 100.0%
9
 100.0%
19
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 9 participants 19 participants
43  (10.83) 39  (13.26) 41  (12.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 9 participants 19 participants
Female
6
  60.0%
3
  33.3%
9
  47.4%
Male
4
  40.0%
6
  66.7%
10
  52.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Switzerland Number Analyzed 10 participants 9 participants 19 participants
10 9 19
1.Primary Outcome
Title Number of Days Until First On-study Relapse
Hide Description Patients were followed-up during 12 months and time to first on-study relapse from randomization was recorded.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and randomized patients fulfilled the criteria for analysis.
Arm/Group Title Natalizumab Interferon-beta-1b
Hide Arm/Group Description:
Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers' instructions.
250 mcg (8 MIU) subcutaneous injections every other day
Overall Number of Participants Analyzed 10 9
Median (Full Range)
Unit of Measure: days
NA [1] 
(NA to NA)
103
(103 to 103)
[1]
This value is not available, because zero patients experienced a relapse.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Natalizumab, Interferon-beta-1b
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments No statistical hypothesis tests for efficacy were performed as this was a pilot study serving to generate first data and hypotheses.
Statistical Test of Hypothesis P-Value 0.125
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Relapses
Hide Description [Not Specified]
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and randomized patients were analyzed.
Arm/Group Title Natalizumab Interferon-beta-1b
Hide Arm/Group Description:
Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers' instructions.
250 mcg (8 MIU) subcutaneous injections every other day
Overall Number of Participants Analyzed 10 9
Measure Type: Number
Unit of Measure: participants
0 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Natalizumab, Interferon-beta-1b
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.447
Comments [Not Specified]
Method non-parametric
Comments [Not Specified]
3.Secondary Outcome
Title Number of Relapses
Hide Description [Not Specified]
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Natalizumab Interferon-beta-1b
Hide Arm/Group Description:
Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers' instructions.
250 mcg (8 MIU) subcutaneous injections every other day
Overall Number of Participants Analyzed 10 9
Measure Type: Number
Unit of Measure: number of events
0 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Natalizumab, Interferon-beta-1b
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.447
Comments [Not Specified]
Method non-parametric
Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Relapse Free Patients
Hide Description [Not Specified]
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Natalizumab Interferon-beta-1b
Hide Arm/Group Description:

Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers’ instructions.

Natalizumab: Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers’ instructions.

250 mcg (8 MIU) subcutaneous injections every other day

interferon beta-1b: Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 month at study entry. After a wash-out period of one month, interferon-beta-1b will be administered subcutaneously every other day as indicated by the manufacturers' instructions including the stepwise up-titration scheme as recommended for treatment start. The final dose of interferon beta-1b is 250 mcg (8 million International Units [MIU])

Overall Number of Participants Analyzed 10 9
Measure Type: Number
Unit of Measure: participants
10 7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Natalizumab, Interferon-beta-1b
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.206
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title Severity of Relapses
Hide Description Change of Expanded Disability Status Scale (EDSS 1-10). Higher values represent a worser outcome.
Time Frame 12 months vs baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Natalizumab Interferon-beta-1b
Hide Arm/Group Description:

Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers’ instructions.

Natalizumab: Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers’ instructions.

250 mcg (8 MIU) subcutaneous injections every other day

interferon beta-1b: Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 month at study entry. After a wash-out period of one month, interferon-beta-1b will be administered subcutaneously every other day as indicated by the manufacturers' instructions including the stepwise up-titration scheme as recommended for treatment start. The final dose of interferon beta-1b is 250 mcg (8 million International Units [MIU])

Overall Number of Participants Analyzed 10 9
Median (Full Range)
Unit of Measure: units on a scale
0
(0 to 0)
0.5
(0.5 to 1.5)
6.Secondary Outcome
Title MRI Parameters
Hide Description Number of new T2-hyperintense lesions, Number of Gd-enhancing lesions on T1-weighted images. Assessments at month 3, 6, 9, 12, 18, 24.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled and randomized patients were analyzed.
Arm/Group Title Natalizumab Interferon-beta-1b
Hide Arm/Group Description:
Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers' instructions.
250 mcg (8 MIU) subcutaneous injections every other day
Overall Number of Participants Analyzed 10 9
Median (Full Range)
Unit of Measure: Lesions
nT2L month 3
0
(0 to 1)
0.5
(0 to 2)
nT2L month 6
0
(0 to 2)
1.5
(0 to 9)
nT2L month 9
0
(0 to 0)
0.5
(0 to 6)
nT2L month 12
0
(0 to 0)
0
(0 to 12)
GD+L month 3
0
(0 to 0)
0
(0 to 1)
GD+L month 6
0
(0 to 0)
0
(0 to 5)
GD+L month 9
0
(0 to 0)
0
(0 to 1)
GD+L month 12
0
(0 to 1)
0
(0 to 2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Natalizumab, Interferon-beta-1b
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments No statistical hypothesis tests for efficacy were performed, as this was pilot study serving to generate first data and hypotheses.
Statistical Test of Hypothesis P-Value 0.234
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments p-value refers to nT2L at month 12
7.Secondary Outcome
Title Number of Patients With Adverse Events
Hide Description Recording and reporting according to regulations. Monthly assessments or if necessary.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All patients enrolled and randomized were analyzed.
Arm/Group Title Natalizumab Interferon-beta-1b
Hide Arm/Group Description:
Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers' instructions.
250 mcg (8 MIU) subcutaneous injections every other day
Overall Number of Participants Analyzed 10 9
Measure Type: Number
Unit of Measure: participants
Number of patients with infections 7 4
Number of patients with injections site reactions 0 4
8.Secondary Outcome
Title Number of Infections
Hide Description [Not Specified]
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Natalizumab Interferon-beta-1b
Hide Arm/Group Description:
Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers' instructions.
250 mcg (8 MIU) subcutaneous injections every other day
Overall Number of Participants Analyzed 10 9
Measure Type: Number
Unit of Measure: events
25 8
Time Frame Adverse events were collected during the 12 months of the trial
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Natalizumab Interferon-beta-1b
Hide Arm/Group Description Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers’ instructions. 250 mcg (8 MIU) subcutaneous injections every other day
All-Cause Mortality
Natalizumab Interferon-beta-1b
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Natalizumab Interferon-beta-1b
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/10 (10.00%)      0/9 (0.00%)    
Gastrointestinal disorders     
gastroenteritis * [1]  1/10 (10.00%)  1 0/9 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
One patient in the NTZ arm experienced a gastroenteritis requiring his hospitalisation. The patient recovered without sequelae and continued the study. The adverse event was judged to be unrelated to the study medication.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Natalizumab Interferon-beta-1b
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/10 (70.00%)      7/9 (77.78%)    
Infections and infestations     
Infection   7/10 (70.00%)  7 3/9 (33.33%)  3
Investigations     
Injection site reaction  0/10 (0.00%)  0 4/9 (44.44%)  4
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Claudio Globbi, Dr. med.
Organization: Ospedale Civico
Phone: +41 91 811 6921
Other Publications:
Responsible Party: Claudio Gobbi, Ospedale Civico, Lugano
ClinicalTrials.gov Identifier: NCT01144052     History of Changes
Other Study ID Numbers: EOC.NC.09.01
First Submitted: June 11, 2010
First Posted: June 15, 2010
Results First Submitted: October 31, 2013
Results First Posted: April 17, 2014
Last Update Posted: April 17, 2014