Trial Outcomes & Findings for Secukinumab Efficacy and Safety Study in Patients With Rheumatoid Arthritis and Inadequate Response to Anti-TNFα Agents. (NCT NCT01770379)
NCT ID: NCT01770379
Last Updated: 2016-07-21
Results Overview
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.
TERMINATED
PHASE3
242 participants
Week 24
2016-07-21
Participant Flow
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.
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).
Participant milestones
| Measure |
AIN457 75 mg
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
|
AIN457 150mg
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
|
Placebo
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 Study
STARTED
|
80
|
81
|
81
|
|
Overall Study
COMPLETED
|
41
|
37
|
39
|
|
Overall Study
NOT COMPLETED
|
39
|
44
|
42
|
Reasons for withdrawal
| Measure |
AIN457 75 mg
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
|
AIN457 150mg
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
|
Placebo
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 Study
Technical issues
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
7
|
10
|
7
|
|
Overall Study
study terminated by sponsor
|
22
|
23
|
22
|
|
Overall Study
Protocol Violation
|
0
|
1
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
2
|
|
Overall Study
Lack of Efficacy
|
8
|
6
|
6
|
|
Overall Study
Adverse Event
|
1
|
3
|
2
|
Baseline Characteristics
Secukinumab Efficacy and Safety Study in Patients With Rheumatoid Arthritis and Inadequate Response to Anti-TNFα Agents.
Baseline characteristics by cohort
| Measure |
AIN457 75 mg
n=80 Participants
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
|
AIN457 150mg
n=81 Participants
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
|
Placebo
n=81 Participants
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
n=242 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
70 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
69 Participants
n=5 Participants
|
201 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
10 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
70 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
202 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
40 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Week 24Population: Full analysis set (FAS): The FAS was comprised of all patients from the randomized set to whom study treatment had been assigned.
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.
Outcome measures
| Measure |
AIN457 75 mg
n=80 Participants
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
|
AIN457 150mg
n=81 Participants
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
|
Placebo
n=81 Participants
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)
|
|---|---|---|---|
|
Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20).
|
37.5 percentage of participants
|
38.3 percentage of participants
|
27.2 percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: Full analysis set (FAS): The FAS was comprised of all patients from the randomized set to whom study treatment had been assigned.
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.
Outcome measures
| Measure |
AIN457 75 mg
n=80 Participants
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
|
AIN457 150mg
n=81 Participants
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
|
Placebo
n=81 Participants
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)
|
|---|---|---|---|
|
Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP)
|
-1.56 Units on a scale
Standard Error 0.149
|
-1.61 Units on a scale
Standard Error 0.148
|
-1.01 Units on a scale
Standard Error 0.176
|
SECONDARY outcome
Timeframe: Week 24Population: Full analysis set (FAS): The FAS was comprised of all patients from the randomized set to whom study treatment had been assigned.
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.
Outcome measures
| Measure |
AIN457 75 mg
n=80 Participants
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
|
AIN457 150mg
n=81 Participants
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
|
Placebo
n=81 Participants
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)
|
|---|---|---|---|
|
Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)
|
-0.42 units on a scale
Standard Error 0.068
|
-0.39 units on a scale
Standard Error 0.068
|
-0.13 units on a scale
Standard Error 0.078
|
SECONDARY outcome
Timeframe: Week 24Population: Full analysis set: the full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment
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.
Outcome measures
| Measure |
AIN457 75 mg
n=80 Participants
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
|
AIN457 150mg
n=81 Participants
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
|
Placebo
n=81 Participants
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)
|
|---|---|---|---|
|
Percentage of Participants Achieving ACR50
|
17.5 Percentage of patients
|
18.5 Percentage of patients
|
13.6 Percentage of patients
|
Adverse Events
Any AIN457 75 mg
Any AIN457 150 mg
Placebo
Serious adverse events
| Measure |
Any AIN457 75 mg
n=115 participants at risk
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
|
Any AIN457 150 mg
n=115 participants at risk
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
|
Placebo
n=79 participants at risk
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)
|
|---|---|---|---|
|
General disorders
Impaired healing
|
0.00%
0/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.00%
0/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Cardiac disorders
Atrial fibrillation
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Ear and labyrinth disorders
Acute vestibular syndrome
|
0.00%
0/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Infections and infestations
Gastroenteritis
|
1.7%
2/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Infections and infestations
Helicobacter infection
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Infections and infestations
Pneumonia
|
0.87%
1/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Injury, poisoning and procedural complications
Synovial rupture
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.87%
1/115
|
1.7%
2/115
|
0.00%
0/79
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma
|
0.00%
0/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Nervous system disorders
Dementia
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.87%
1/115
|
0.00%
0/115
|
0.00%
0/79
|
Other adverse events
| Measure |
Any AIN457 75 mg
n=115 participants at risk
75 mg secukinumab: Patients on secukinumab 75 mg continued to receive secukinumab 75 mg via PFS every 4 weeks regardless of responder status.
|
Any AIN457 150 mg
n=115 participants at risk
150 mg secukinumab: Patients on secukinumab 150 mg continued to receive secukinumab 150 mg via PFS every 4 weeks regardless of responder status.
|
Placebo
n=79 participants at risk
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)
|
|---|---|---|---|
|
Infections and infestations
Bronchitis
|
12.2%
14/115
|
3.5%
4/115
|
5.1%
4/79
|
|
Infections and infestations
Cystitis
|
3.5%
4/115
|
2.6%
3/115
|
1.3%
1/79
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/115
|
2.6%
3/115
|
0.00%
0/79
|
|
Ear and labyrinth disorders
Vertigo
|
0.87%
1/115
|
2.6%
3/115
|
1.3%
1/79
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.7%
2/115
|
2.6%
3/115
|
1.3%
1/79
|
|
Gastrointestinal disorders
Dental caries
|
2.6%
3/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Gastrointestinal disorders
Diarrhoea
|
7.0%
8/115
|
7.8%
9/115
|
1.3%
1/79
|
|
Gastrointestinal disorders
Dyspepsia
|
6.1%
7/115
|
2.6%
3/115
|
0.00%
0/79
|
|
Gastrointestinal disorders
Nausea
|
3.5%
4/115
|
5.2%
6/115
|
1.3%
1/79
|
|
Gastrointestinal disorders
Stomatitis
|
2.6%
3/115
|
0.00%
0/115
|
1.3%
1/79
|
|
Gastrointestinal disorders
Vomiting
|
1.7%
2/115
|
5.2%
6/115
|
1.3%
1/79
|
|
General disorders
Injection site pain
|
4.3%
5/115
|
0.87%
1/115
|
1.3%
1/79
|
|
General disorders
Oedema peripheral
|
0.87%
1/115
|
3.5%
4/115
|
2.5%
2/79
|
|
General disorders
Pyrexia
|
4.3%
5/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Infections and infestations
Influenza
|
4.3%
5/115
|
1.7%
2/115
|
0.00%
0/79
|
|
Infections and infestations
Labyrinthitis
|
0.00%
0/115
|
0.00%
0/115
|
2.5%
2/79
|
|
Infections and infestations
Lower respiratory tract infection
|
2.6%
3/115
|
0.00%
0/115
|
0.00%
0/79
|
|
Infections and infestations
Nasopharyngitis
|
21.7%
25/115
|
20.0%
23/115
|
10.1%
8/79
|
|
Infections and infestations
Rhinitis
|
4.3%
5/115
|
4.3%
5/115
|
1.3%
1/79
|
|
Infections and infestations
Sinusitis
|
1.7%
2/115
|
1.7%
2/115
|
2.5%
2/79
|
|
Infections and infestations
Upper respiratory tract infection
|
7.0%
8/115
|
7.8%
9/115
|
3.8%
3/79
|
|
Infections and infestations
Urinary tract infection
|
7.8%
9/115
|
1.7%
2/115
|
2.5%
2/79
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.87%
1/115
|
2.6%
3/115
|
0.00%
0/79
|
|
Investigations
Weight increased
|
1.7%
2/115
|
2.6%
3/115
|
0.00%
0/79
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.3%
5/115
|
1.7%
2/115
|
3.8%
3/79
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.5%
4/115
|
3.5%
4/115
|
0.00%
0/79
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/115
|
3.5%
4/115
|
0.00%
0/79
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
4.3%
5/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/115
|
0.87%
1/115
|
2.5%
2/79
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
9.6%
11/115
|
8.7%
10/115
|
7.6%
6/79
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid nodule
|
0.00%
0/115
|
2.6%
3/115
|
0.00%
0/79
|
|
Nervous system disorders
Dizziness
|
2.6%
3/115
|
3.5%
4/115
|
1.3%
1/79
|
|
Nervous system disorders
Headache
|
5.2%
6/115
|
8.7%
10/115
|
2.5%
2/79
|
|
Psychiatric disorders
Insomnia
|
2.6%
3/115
|
0.87%
1/115
|
0.00%
0/79
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.4%
12/115
|
1.7%
2/115
|
0.00%
0/79
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.87%
1/115
|
0.87%
1/115
|
2.5%
2/79
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.87%
1/115
|
2.6%
3/115
|
0.00%
0/79
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/115
|
0.00%
0/115
|
2.5%
2/79
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.3%
5/115
|
3.5%
4/115
|
1.3%
1/79
|
|
Vascular disorders
Hypertension
|
4.3%
5/115
|
5.2%
6/115
|
0.00%
0/79
|
Additional Information
Clinical Disclosure Office
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER