Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Secukinumab Efficacy and Safety Study in Patients With Rheumatoid Arthritis and Inadequate Response to Anti-TNFα Agents. (REASSURE2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01770379
Recruitment Status : Terminated
First Posted : January 17, 2013
Results First Posted : July 21, 2016
Last Update Posted : July 21, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Biological: Secukinumab (AIN457)
Biological: Placebo
Enrollment 242
Recruitment Details Patients received AIN457 75 mg, AIN457 150 mg or placebo as subcutaneous (s.c.) loading dose once weekly at baseline (BSL), Weeks 1, 2, 3 and 4, followed by monthly maintenance starting at Week 4.
Pre-assignment Details At Wk 16, patients were classified as responders or non-responders. Placebo patients who were non responders were rerandomized at Wk 16 to AIN457 75 mg or AIN457 150 mg (1:1). Patients on placebo who were responders continued to receive placebo until Wk 24, these patients were re-randomized to receive AIN457 75 mg or AIN457 150 mg (1:1).
Arm/Group Title AIN457 75 mg AIN457 150mg Placebo
Hide Arm/Group Description 75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status. 150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status. At Wk 16, patients were classified: responders or non-responders. Placebo patients who were non responders were rerandomized at Wk 16 to AIN457 75 mg or AIN457 150 mg (1:1). Patients on placebo who were responders continued to receive placebo until Wk 24, these patients were re-randomized to receive AIN457 75 mg or AIN457 150 mg (1:1)
Period Title: Overall Study
Started 80 81 81
Completed 41 37 39
Not Completed 39 44 42
Reason Not Completed
Technical issues             1             0             0
Withdrawal by Subject             7             10             7
study terminated by sponsor             22             23             22
Protocol Violation             0             1             1
Physician Decision             0             1             2
Lost to Follow-up             0             0             2
Lack of Efficacy             8             6             6
Adverse Event             1             3             2
Arm/Group Title AIN457 75 mg AIN457 150mg Placebo Total
Hide Arm/Group Description 75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status. 150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status. At Wk 16, patients were classified: responders or non-responders. Placebo patients who were non responders were rerandomized at Wk 16 to AIN457 75 mg or AIN457 150 mg (1:1). Patients on placebo who were responders continued to receive placebo until Wk 24, these patients were re-randomized to receive AIN457 75 mg or AIN457 150 mg (1:1) Total of all reporting groups
Overall Number of Baseline Participants 80 81 81 242
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 81 participants 81 participants 242 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
70
  87.5%
62
  76.5%
69
  85.2%
201
  83.1%
>=65 years
10
  12.5%
19
  23.5%
12
  14.8%
41
  16.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 81 participants 81 participants 242 participants
Female
70
  87.5%
67
  82.7%
65
  80.2%
202
  83.5%
Male
10
  12.5%
14
  17.3%
16
  19.8%
40
  16.5%
1.Primary Outcome
Title Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20).
Hide Description

ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient’s assessment of RA pain, patient’s global assessment of disease activity, physician’s global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).

The ACR20 response results at week 24 used non-responder imputation.

Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS was comprised of all patients from the randomized set to whom study treatment had been assigned.
Arm/Group Title AIN457 75 mg AIN457 150mg Placebo
Hide Arm/Group Description:
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
At Wk 16, patients were classified: responders or non-responders. Placebo patients who were non responders were rerandomized at Wk 16 to AIN457 75 mg or AIN457 150 mg (1:1). Patients on placebo who were responders continued to receive placebo until Wk 24, these patients were re-randomized to receive AIN457 75 mg or AIN457 150 mg (1:1)
Overall Number of Participants Analyzed 80 81 81
Measure Type: Number
Unit of Measure: percentage of participants
37.5 38.3 27.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AIN457 75 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
0.79 to 3.03
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AIN457 150mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1574
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.62
Confidence Interval (2-Sided) 95%
0.83 to 3.15
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP)
Hide Description The DAS28 is a measure of disease activity in RA based on Swollen and Tender Joint Counts (out of a total of 28), hsCRP and the Patient’s Global Assessment of Disease Activity. A DAS28 score greater than 5.1 implies active disease, equal to or less than 3.2 low disease activity, and less than 2.6 remission. A negative change from baseline indicates improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS was comprised of all patients from the randomized set to whom study treatment had been assigned.
Arm/Group Title AIN457 75 mg AIN457 150mg Placebo
Hide Arm/Group Description:
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
At Wk 16, patients were classified: responders or non-responders. Placebo patients who were non responders were rerandomized at Wk 16 to AIN457 75 mg or AIN457 150 mg (1:1). Patients on placebo who were responders continued to receive placebo until Wk 24, these patients were re-randomized to receive AIN457 75 mg or AIN457 150 mg (1:1)
Overall Number of Participants Analyzed 80 81 81
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-1.56  (0.149) -1.61  (0.148) -1.01  (0.176)
3.Secondary Outcome
Title Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)
Hide Description The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS was comprised of all patients from the randomized set to whom study treatment had been assigned.
Arm/Group Title AIN457 75 mg AIN457 150 mg Placebo
Hide Arm/Group Description:
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
At Wk 16, patients were classified: responders or non-responders. Placebo patients who were non responders were rerandomized at Wk 16 to AIN457 75 mg or AIN457 150 mg (1:1). Patients on placebo who were responders continued to receive placebo until Wk 24, these patients were re-randomized to receive AIN457 75 mg or AIN457 150 mg (1:1)
Overall Number of Participants Analyzed 80 81 81
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.42  (0.068) -0.39  (0.068) -0.13  (0.078)
4.Secondary Outcome
Title Percentage of Participants Achieving ACR50
Hide Description

ACR50 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient’s assessment of RA pain, patient’s global assessment of disease activity, physician’s global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).

The ACR50 response results at week 24 used non-responder imputation.

Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: the full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment
Arm/Group Title AIN457 75 mg AIN457 150mg Placebo
Hide Arm/Group Description:
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
At Wk 16, patients were classified: responders or non-responders. Placebo patients who were non responders were rerandomized at Wk 16 to AIN457 75 mg or AIN457 150 mg (1:1). Patients on placebo who were responders continued to receive placebo until Wk 24, these patients were re-randomized to receive AIN457 75 mg or AIN457 150 mg (1:1)
Overall Number of Participants Analyzed 80 81 81
Measure Type: Number
Unit of Measure: Percentage of patients
17.5 18.5 13.6
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Any AIN457 75 mg Any AIN457 150 mg Placebo
Hide Arm/Group Description 75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status. 150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status. At Wk 16, patients were classified: responders or non-responders. Placebo patients who were non responders were rerandomized at Wk 16 to AIN457 75 mg or AIN457 150 mg (1:1). Patients on placebo who were responders continued to receive placebo until Wk 24, these patients were re-randomized to receive AIN457 75 mg or AIN457 150 mg (1:1)
All-Cause Mortality
Any AIN457 75 mg Any AIN457 150 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Any AIN457 75 mg Any AIN457 150 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/115 (10.43%)   9/115 (7.83%)   0/79 (0.00%) 
Cardiac disorders       
Atrial fibrillation  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Ear and labyrinth disorders       
Acute vestibular syndrome  1  0/115 (0.00%)  1/115 (0.87%)  0/79 (0.00%) 
General disorders       
Impaired healing  1  0/115 (0.00%)  1/115 (0.87%)  0/79 (0.00%) 
Hepatobiliary disorders       
Cholecystitis acute  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Cholecystitis chronic  1  0/115 (0.00%)  1/115 (0.87%)  0/79 (0.00%) 
Hepatic function abnormal  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Infections and infestations       
Gastroenteritis  1  2/115 (1.74%)  0/115 (0.00%)  0/79 (0.00%) 
Helicobacter infection  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Lower respiratory tract infection  1  0/115 (0.00%)  1/115 (0.87%)  0/79 (0.00%) 
Pneumonia  1  1/115 (0.87%)  1/115 (0.87%)  0/79 (0.00%) 
Pulmonary tuberculosis  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Injury, poisoning and procedural complications       
Synovial rupture  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Tendon rupture  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  0/115 (0.00%)  1/115 (0.87%)  0/79 (0.00%) 
Osteoarthritis  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Osteonecrosis  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Pain in extremity  1  0/115 (0.00%)  1/115 (0.87%)  0/79 (0.00%) 
Rheumatoid arthritis  1  1/115 (0.87%)  2/115 (1.74%)  0/79 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Invasive ductal breast carcinoma  1  0/115 (0.00%)  1/115 (0.87%)  0/79 (0.00%) 
Uterine leiomyoma  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Nervous system disorders       
Dementia  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Renal and urinary disorders       
Nephrolithiasis  1  0/115 (0.00%)  1/115 (0.87%)  0/79 (0.00%) 
Skin and subcutaneous tissue disorders       
Skin ulcer  1  1/115 (0.87%)  0/115 (0.00%)  0/79 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Any AIN457 75 mg Any AIN457 150 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   77/115 (66.96%)   63/115 (54.78%)   35/79 (44.30%) 
Ear and labyrinth disorders       
Vertigo  1  1/115 (0.87%)  3/115 (2.61%)  1/79 (1.27%) 
Gastrointestinal disorders       
Abdominal pain upper  1  2/115 (1.74%)  3/115 (2.61%)  1/79 (1.27%) 
Dental caries  1  3/115 (2.61%)  0/115 (0.00%)  0/79 (0.00%) 
Diarrhoea  1  8/115 (6.96%)  9/115 (7.83%)  1/79 (1.27%) 
Dyspepsia  1  7/115 (6.09%)  3/115 (2.61%)  0/79 (0.00%) 
Nausea  1  4/115 (3.48%)  6/115 (5.22%)  1/79 (1.27%) 
Stomatitis  1  3/115 (2.61%)  0/115 (0.00%)  1/79 (1.27%) 
Vomiting  1  2/115 (1.74%)  6/115 (5.22%)  1/79 (1.27%) 
General disorders       
Injection site pain  1  5/115 (4.35%)  1/115 (0.87%)  1/79 (1.27%) 
Oedema peripheral  1  1/115 (0.87%)  4/115 (3.48%)  2/79 (2.53%) 
Pyrexia  1  5/115 (4.35%)  0/115 (0.00%)  0/79 (0.00%) 
Infections and infestations       
Bronchitis  1  14/115 (12.17%)  4/115 (3.48%)  4/79 (5.06%) 
Cystitis  1  4/115 (3.48%)  3/115 (2.61%)  1/79 (1.27%) 
Gastroenteritis  1  0/115 (0.00%)  3/115 (2.61%)  0/79 (0.00%) 
Influenza  1  5/115 (4.35%)  2/115 (1.74%)  0/79 (0.00%) 
Labyrinthitis  1  0/115 (0.00%)  0/115 (0.00%)  2/79 (2.53%) 
Lower respiratory tract infection  1  3/115 (2.61%)  0/115 (0.00%)  0/79 (0.00%) 
Nasopharyngitis  1  25/115 (21.74%)  23/115 (20.00%)  8/79 (10.13%) 
Rhinitis  1  5/115 (4.35%)  5/115 (4.35%)  1/79 (1.27%) 
Sinusitis  1  2/115 (1.74%)  2/115 (1.74%)  2/79 (2.53%) 
Upper respiratory tract infection  1  8/115 (6.96%)  9/115 (7.83%)  3/79 (3.80%) 
Urinary tract infection  1  9/115 (7.83%)  2/115 (1.74%)  2/79 (2.53%) 
Injury, poisoning and procedural complications       
Ligament sprain  1  1/115 (0.87%)  3/115 (2.61%)  0/79 (0.00%) 
Investigations       
Weight increased  1  2/115 (1.74%)  3/115 (2.61%)  0/79 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  5/115 (4.35%)  2/115 (1.74%)  3/79 (3.80%) 
Back pain  1  4/115 (3.48%)  4/115 (3.48%)  0/79 (0.00%) 
Muscle spasms  1  0/115 (0.00%)  4/115 (3.48%)  0/79 (0.00%) 
Musculoskeletal pain  1  5/115 (4.35%)  1/115 (0.87%)  0/79 (0.00%) 
Pain in extremity  1  0/115 (0.00%)  1/115 (0.87%)  2/79 (2.53%) 
Rheumatoid arthritis  1  11/115 (9.57%)  10/115 (8.70%)  6/79 (7.59%) 
Rheumatoid nodule  1  0/115 (0.00%)  3/115 (2.61%)  0/79 (0.00%) 
Nervous system disorders       
Dizziness  1  3/115 (2.61%)  4/115 (3.48%)  1/79 (1.27%) 
Headache  1  6/115 (5.22%)  10/115 (8.70%)  2/79 (2.53%) 
Psychiatric disorders       
Insomnia  1  3/115 (2.61%)  1/115 (0.87%)  0/79 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  12/115 (10.43%)  2/115 (1.74%)  0/79 (0.00%) 
Oropharyngeal pain  1  1/115 (0.87%)  1/115 (0.87%)  2/79 (2.53%) 
Rhinorrhoea  1  1/115 (0.87%)  3/115 (2.61%)  0/79 (0.00%) 
Skin and subcutaneous tissue disorders       
Eczema  1  0/115 (0.00%)  0/115 (0.00%)  2/79 (2.53%) 
Rash  1  5/115 (4.35%)  4/115 (3.48%)  1/79 (1.27%) 
Vascular disorders       
Hypertension  1  5/115 (4.35%)  6/115 (5.22%)  0/79 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
The study was terminated early due to the decision (unrelated to safety) to discontinue the clinical development program for secukinumab in Rheumatoid Arthritis, with last patient last visit (LPLV) on 11-May-2015.
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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01770379     History of Changes
Other Study ID Numbers: CAIN457F2311
2011-006058-94 ( EudraCT Number )
First Submitted: October 16, 2012
First Posted: January 17, 2013
Results First Submitted: May 3, 2016
Results First Posted: July 21, 2016
Last Update Posted: July 21, 2016