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This study aims to confirm if patients with a specific biomarker might have a better response to secukinumab treatment. To meet this purpose, exploratory biomarker studies will be done. The goals of these exploratory studies are to (1) find biomarkers that will identify persons with rheumatoid arthritis who will have the best possible response to secukinumab and (2) to identify persons who will have fewer side effects in order to maximize their benefit from secukinumab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Secukinumab | Experimental | 10 mg/kg intravenous (I.V.) |
|
| Placebo | Placebo Comparator | Placebo I.V. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Matching placebo to secukinumab I.V. |
| |
| Secukinumab |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20 ) in Association With the Presence or Absence of the HLA-DRB1 *4 Allelic Group | A participant was considered to be a responder according to the ACR20 criteria if the participant had at least 20% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR). | 12 weeks |
| Change From Baseline in Disease Activity Score 28 (DAS28) in Association With the Presence or Absence of HLA-DRB1 04 | The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement. | baseline, 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieve ACR50 and ACR70 With the Presence/Absence of the HLA-DRB1*04 Allelic Group | A participant was considered to be a responder according to the ACR50 or ACR70 criteria if the participant had at least 50% or 70% improvement, respectively, in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR). |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Phoenix | Arizona | 85023 | United States | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26268815 | Derived | Burmester GR, Durez P, Shestakova G, Genovese MC, Schulze-Koops H, Li Y, Wang YA, Lewitzky S, Koroleva I, Berneis AA, Lee DM, Hueber W. Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin-17A monoclonal antibody secukinumab in active rheumatoid arthritis. Rheumatology (Oxford). 2016 Jan;55(1):49-55. doi: 10.1093/rheumatology/kev258. Epub 2015 Aug 12. |
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One hundred participants received study treatment in part 1. Ten participants discontinued during part 1. At the end of part 1, 76 participants were eligible to take secukinumab treatment in part 2.
The study included a 12 week, randomized, double blind phase (part 1), a 40 week, open label phase (part 2), and a 3 month safety follow-up. Participants from the secukinumab arm, who completed part 1 and had an ACR50 or greater response at week 12, and participants from the placebo arm, who completed part 1, were eligible for the open label phase.
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| ID | Title | Description |
|---|---|---|
| FG000 | Secukinumab | 10 mg/kg intravenous (I.V.) |
| FG001 | Placebo | Placebo i.v. |
| FG002 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part 1 |
|
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| Drug |
In part 1 (blinded period), participants randomized to secukinumab received 10 mg/kg I.V.. Participants, enrolled in part 2 (open label), received secukinumab 300 mg subcutaneous. |
|
|
| 12 weeks |
| Change From Baseline in DAS28 in Association With the Presence or Absence of HLA-DRB1 *SE (Positive), HLA-DRB1 *401 (Carrier) and HLA-DRB1 Position 11 V/L and in Association With Other Biomarkers | The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement. | baseline, 12 weeks |
| Tuscon |
| Arizona |
| 85724 |
| United States |
| Novartis Investigative Site | Anahiem | California | 92804 | United States |
| Novartis Investigative Site | Clearwater | Florida | 33756 | United States |
| Novartis Investigative Site | Coral Gables | Florida | 33134 | United States |
| Novartis Investigative Site | Fleming Island | Florida | 32003 | United States |
| Novartis Investigative Site | Miami | Florida | 33143 | United States |
| Novartis Investigative Site | Pinellas Park | Florida | 33781 | United States |
| Novartis Investigative Site | Venice | Florida | 34292 | United States |
| Novartis Investigative Site | Marietta | Georgia | 30060 | United States |
| Novartis Investigative Site | South Bend | Indiana | 46601 | United States |
| Novartis Investigative Site | Springfield | Missouri | 65807 | United States |
| Novartis Investigative Site | Albuquerque | New Mexico | 87102 | United States |
| Novartis Investigative Site | Statesville | North Carolina | 28625 | United States |
| Novartis Investigative Site | Oklahoma City | Oklahoma | 73112 | United States |
| Novartis Investigative Site | San Antonio | Texas | 78217 | United States |
| Novartis Investigative Site | Brussels | 1200 | Belgium |
| Novartis Investigative Site | Kortrijk | 8500 | Belgium |
| Novartis Investigative Site | Berlin | 10117 | Germany |
| Novartis Investigative Site | Berlin | 14059 | Germany |
| Novartis Investigative Site | Frankfurt am Main | 60528 | Germany |
| Novartis Investigative Site | Hamburg | GmbH 22769 | Germany |
| Novartis Investigative Site | Herne | 44649 | Germany |
| Novartis Investigative Site | Leipzig | 04103 | Germany |
| Novartis Investigative Site | Magdeburg | 39120 | Germany |
| Novartis Investigative Site | München | 80336 | Germany |
| Novartis Investigative Site | Smolensk | Russia | 214019 | Russia |
| Novartis Investigative Site | Moscow | 117049 | Russia |
| Novartis Investigative Site | Nizhny Novgorod | 603018 | Russia |
| Novartis Investigative Site | Petrozavodsk | 185019 | Russia |
| Novartis Investigative Site | Saint Petersburg | 194104 | Russia |
| Novartis Investigative Site | Tver' | 170036 | Russia |
| Novartis Investigative Site | Yaroslavl | 150030 | Russia |
| Novartis Investigative Site | Yaroslavl | 150062 | Russia |
| Novartis Investigative Site | Manchester | Manchester | M41 5SL | United Kingdom |
| Novartis Investigative Site | Belfast | BT2 7BA | United Kingdom |
| Group 1 |
Part 1: secukinumab 6 x 10 mg/kg i.v.; Part 2: secukinumab 300 mg sc monthly |
| FG003 | Group 2 | Part 1: secukinumab 6 x 10 mg/kg i.v.; part 2: no study treatment |
| FG004 | Group 3 | Part 1: placebo; Part 2: secukinumab 4 x 300 mg sc loading dose (at weeks 12, 13, 14 and 16), then 300 mg sc monthly |
| FG005 | Group 4 | Part 1: placebo; Part 2: no study treatment |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Part 2 |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Secukinumab | 10 mg/kg intravenous (I.V.) |
| BG001 | Placebo | Placebo i.v. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20 ) in Association With the Presence or Absence of the HLA-DRB1 *4 Allelic Group | A participant was considered to be a responder according to the ACR20 criteria if the participant had at least 20% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR). | Participants, who completed part 1, were included in the analysis. | Posted | Number | Percentage of participants | 12 weeks |
|
|
| ||||||||||||||||||||||||||||||||||||
| Primary | Change From Baseline in Disease Activity Score 28 (DAS28) in Association With the Presence or Absence of HLA-DRB1 04 | The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement. | Participants, who completed part 1, were included in the analysis. | Posted | Least Squares Mean | Standard Error | score on a scale | baseline, 12 weeks |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Who Achieve ACR50 and ACR70 With the Presence/Absence of the HLA-DRB1*04 Allelic Group | A participant was considered to be a responder according to the ACR50 or ACR70 criteria if the participant had at least 50% or 70% improvement, respectively, in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR). | Participants, who completed part 1, were included in the analysis. | Posted | Number | Percentage of participants | 12 weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in DAS28 in Association With the Presence or Absence of HLA-DRB1 *SE (Positive), HLA-DRB1 *401 (Carrier) and HLA-DRB1 Position 11 V/L and in Association With Other Biomarkers | The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement. | Participants, who completed part 1, were included in the analysis. Statistical analysis was not done on the other biomarkers: osteoprotegerin (OPG), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (CCP) and hsCRP. Therefore, data is provided for the alleles only. | Posted | Least Squares Mean | Standard Error | score on a scale | baseline, 12 weeks |
|
Not provided
Adverse events that occurred in subjects after they discontinued during or at the end of Part 1 are not included in the Part 2 safety analysis. Therefore, treatment groups from Part 1 and groups 1 and 3 from Part 2 are presented only.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Secukinumab | 10mg/kg i.v. | 4 | 68 | 13 | 68 | ||
| EG001 | Placebo | Placebo i.v. | 2 | 32 | 9 | 32 | ||
| EG002 | Group 1 | Part 1: secukinumab 6 x 10 mg/kg i.v.; Part 2: secukinumab 300 mg sc monthly | 4 | 49 | 15 | 49 | ||
| EG003 | Group 3 | Part 1: placebo; Part 2: secukinumab 4 x 300 mg sc loading dose (at weeks 12, 13, 14 and 16), then 300 mg sc monthly | 4 | 27 | 12 | 27 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina pectoris | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Multi-organ failure | General disorders | MedDRA | Systematic Assessment |
| |
| Abscess limb | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Lobar pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Tendon disorder | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Adenocarcinoma gastric | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Lung carcinoma cell type unspecified stage IV | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Ovarian adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA | Systematic Assessment |
| |
| Acute prerenal failure | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Idiopathic pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Hidradenitis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Arteriosclerosis | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Vasculitis necrotising | Vascular disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dry eye | Eye disorders | MedDRA | Systematic Assessment |
| |
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA | Systematic Assessment |
| |
| Injection site haematoma | General disorders | MedDRA | Systematic Assessment |
| |
| Injection site induration | General disorders | MedDRA | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Respiratory tract infection viral | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Xeroderma | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C555450 | secukinumab |
Not provided
Not provided
Not provided
| Death |
|
| Administrative problems |
|
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Lack of Efficacy |
|
| Adverse Event |
|
| Male |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|
Placebo i.v.
|
|