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Evaluate the safety, tolerability and pharmacokinetics of AIN457 when administered as a single dose (intravenous infusion) in patients with active rheumatoid arthritis in combination with a stable dose of methotrexate. And to compare efficacy on the dose groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 - AIN457A 0.3 mg/kg | Experimental | AIN457A 0.3 mg/kg was administered intravenously as a single dose. |
|
| Part 1 - AIN457A 1.0 mg/kg | Experimental | AIN457A 1.0 mg/kg was administered intravenously as a single dose. |
|
| Part 1 - AIN457A 3.0 mg/kg | Experimental | AIN457A 3.0 mg/kg was administered intravenously as a single dose. |
|
| Part 1 - AIN457A 10 mg/kg | Experimental | AIN457A 10.0 mg/kg was administered intravenously as a single dose. |
|
| Part 1 - Placebo | Placebo Comparator | Placebo to AIN457A was administered intravenously as a single dose. |
|
| Parts 2 and 3 - AIN457A 1.0 mg/kg | Experimental | AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AIN457 | Biological | AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20) | Clinical response to treatment was assessed according to ACR20 criteria. A participant was defined as an ACR20 responder if the following 3 conditions were met: 1) ≥20% improvement in the number of tender joints, 2) ≥20% improvement in the number of swollen joint and 3) ≥20% improvement in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant. | Day 43 |
| Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 29, 36, 43, 57, 71, 85, 99 and 113. | Day 113 |
| PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Day 113 |
| PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Day 113 |
| PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 Participants |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70 | Clinical response to treatment was assessed according to ACR50 and ACR70 criteria. A participant was defined as an ACR50 or ACR70 responder if the following 3 conditions were met: 1) improvement of ≥50% or ≥ 70%, respectively, in the number of tender joints, 2) improvement of ≥50% or ≥ 70%, respectively, in the number of swollen joints and 3) improvement of ≥50% or ≥ 70%, respectively, in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant |
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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 |
| Novartis | Novartis investigator site | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Anniston | Alabama | 36207-5710 | United States | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20926833 | Derived | Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH; Psoriasis Study Group; Durez P, Tak PP, Gomez-Reino JJ; Rheumatoid Arthritis Study Group; Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD; Uveitis Study Group; Rose K, Haider A, Di Padova F. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 2010 Oct 6;2(52):52ra72. doi: 10.1126/scitranslmed.3001107. |
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In parts 1 and 2, participants were randomized 3:1 to receive AIN457A or placebo. In part 3, participants were randomized 1:1 to receive AIN457A or placebo.
Part 1: single dose escalation - sequential cohorts of patients and healthy volunteers received AIN457A or placebo. Part 2: multiple dose escalation - sequential cohorts of patients received 2 doses of AIN457A or placebo. Part 3: patients received 2 doses of AIN457 10 mg/kg (or the maximum tolerated dose) or placebo.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 - AIN457A 0.3 mg/kg | AIN457A 0.3 mg/kg was administered intravenously as a single dose. |
| FG001 | Part 1 - AIN457A 1.0 mg/kg | AIN457A 1.0 mg/kg was administered intravenously as a single dose. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part 1 |
|
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|
| Parts 2 and 3 - AIN457A 3.0 mg/kg | Experimental | AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
|
| Parts 2 and 3 - AIN457A 10 mg/kg | Experimental | AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
|
| Parts 2 and 3 - Placebo | Placebo Comparator | Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
|
| Part 1 - Healthy Volunteers - AIN457A 3 mg/kg | Experimental | AIN457A 3.0 mg/kg was administered intravenously as a single dose. |
|
| Part 1 - Healthy Volunteers - AIN457A 10 mg/kg | Experimental | AIN457A 10 mg/kg was administered intravenously as a single dose. |
|
| Part 1 - Healthy Volunteers - Placebo | Placebo Comparator | Placebo to AIN457A was administered intravenously as a single dose. |
|
| Placebo | Drug | Placebo to AIN457 |
|
Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. |
| Day 113 |
| PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Day 113 |
| PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Day 113 |
| Pharmacokinetics PK of AIN457: Tmax in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Day 113 |
| Pharmacokinetics PK of AIN457: Cmax in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Day 113 |
| Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Day 113 |
| Pharmacokinetics PK of AIN457: Vz in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Day 113 |
| Pharmacokinetics PK of AIN457: CL in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Day 113 |
| Pharmacokinetics PK of AIN457: T1/2 in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Day 113 |
| Day 43 |
| Disease Activity Score (DAS28) of Parts 2 and 3 Participants | The DAS28 is a composite score based on tender and swollen joint counts, C reactive protein (CRP) concentrations, and the participant's global disease activity based on a visual analogue scale (VAS). The tender joint count (based on 28 joints) was calculated by scoring several different aspects of tenderness as assessed by pressure and joint manipulation on physical examination. The information on various types of tenderness was then collapsed into a single tender versus non-tender dichotomy, and the number of joints that were classified as tender was recorded. The swollen joint count was calculated in the same manner. For CRP concentrations, blood samples were collected and sent to a central laboratory for assessment. For the VAS assessment, the participant used a 100 mm horizontal VAS to assess the severity of his or her arthritis where 0 = none and 100 = most severe. DAS28 scores range from <2.6 (disease remission) to >5.1 (high disease activity). | Day 43 |
| Tucson |
| Arizona |
| 85724 |
| United States |
| Novartis Investigative Site | Largo | Florida | 33773 | United States |
| Novartis Investigative Site | Ocala | Florida | 34471 | United States |
| Novartis Investigative Site | Palm Harbor | Florida | 34684 | United States |
| Novartis Investigative Site | Port Orange | Florida | 32127 | United States |
| Novartis Investigative Site | Madisonville | Kentucky | 42431 | United States |
| Novartis Investigative Site | St Louis | Missouri | 63110 | United States |
| Novartis Investigative Site | Omaha | Nebraska | 68131-2197 | United States |
| Novartis Investigative Site | Oklahoma City | Oklahoma | 73103 | United States |
| Novartis Investigative Site | Bend | Oregon | 97701 | United States |
| Novartis Investigative Site | Duncansville | Pennsylvania | 16635 | United States |
| Novartis Investigative Site | Brussels | 1200 | Belgium |
| Novartis Investigative Site | Merksem | 2170 | Belgium |
| Novartis Investigative Site | Bad Nauheim | 61231 | Germany |
| Novartis Investigative Site | Erlangen | 91054 | Germany |
| Novartis Investigative Site | München | 80336 | Germany |
| Novartis Investigative Site | Amsterdam | 1105 AZ | Netherlands |
| Novartis Investigative Site | Nijmegen | 6525 GA | Netherlands |
| Novartis Investigative Site | Singapore | Singapore | 119074 | Singapore |
| Novartis Investigative Site | Singapore | Singapore | 529889 | Singapore |
| Novartis Investigative Site | A Coruña | Galicia | 15006 | Spain |
| Novartis Investigative Site | Santiago de Compostela | Galicia | 15706 | Spain |
| Novartis Investigative Site | Guadalajara | 19002 | Spain |
| FG002 | Part 1 - AIN457A 3.0 mg/kg | AIN457A 3.0 mg/kg was administered intravenously as a single dose. |
| FG003 | Part 1 - AIN457A 10 mg/kg | AIN457A 10.0 mg/kg was administered intravenously as a single dose. |
| FG004 | Part 1 - Placebo | Placebo to AIN457A was administered intravenously as a single dose. |
| FG005 | Parts 2 and 3 - AIN457A 1.0 mg/kg | AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| FG006 | Parts 2 and 3 - AIN457A 3.0 mg/kg | AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| FG007 | Parts 2 and 3 - AIN457A 10 mg/kg | AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| FG008 | Parts 2 and 3 - Placebo | Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| FG009 | Part 1 - Healthy Volunteers - AIN457A 3 mg/kg | AIN457A 3.0 mg/kg was administered intravenously as a single dose. |
| FG010 | Part 1 - Healthy Volunteers - AIN457A 10 mg/kg | AIN457A 10 mg/kg was administered intravenously as a single dose. |
| FG011 | Part 1 - Healthy Volunteers - Placebo | Placebo to AIN457A was administered intravenously as a single dose. |
| COMPLETED |
|
| NOT COMPLETED |
|
| Parts 2 and 3 |
|
|
| Healthy Volunteers |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 - AIN457A 0.3 mg/kg | AIN457A 0.3 mg/kg was administered intravenously as a single dose. |
| BG001 | Part 1 - AIN457A 1.0 mg/kg | AIN457A 1.0 mg/kg was administered intravenously as a single dose. |
| BG002 | Part 1 - AIN457A 3.0 mg/kg | AIN457A 3.0 mg/kg was administered intravenously as a single dose. |
| BG003 | Part 1 - AIN457A 10 mg/kg | AIN457A 10.0 mg/kg was administered intravenously as a single dose. |
| BG004 | Part 1 - Placebo | Placebo to AIN457A was administered intravenously as a single dose. |
| BG005 | Parts 2 and 3 - AIN457A 1.0 mg/kg | AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| BG006 | Parts 2 and 3 - AIN457A 3.0 mg/kg | AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| BG007 | Parts 2 and 3 - AIN457A 10 mg/kg | AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| BG008 | Parts 2 and 3 - Placebo | Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. |
| BG009 | Part 1 - Healthy Volunteers - AIN457A 3 mg/kg | AIN457A 3.0 mg/kg was administered intravenously as a single dose. |
| BG010 | Part 1 - Healthy Volunteers - AIN457A 10 mg/kg | AIN457A 10 mg/kg was administered intravenously as a single dose. |
| BG011 | Part 1 - Healthy Volunteers - Placebo | Placebo to AIN457A was administered intravenously as a single dose. |
| BG012 | 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 Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20) | Clinical response to treatment was assessed according to ACR20 criteria. A participant was defined as an ACR20 responder if the following 3 conditions were met: 1) ≥20% improvement in the number of tender joints, 2) ≥20% improvement in the number of swollen joint and 3) ≥20% improvement in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant. | The analysis was performed on the 10 mg and placebo treatment arms of the parts 2 and 3 participants. | Posted | Number | percentage of participants | Day 43 |
|
|
| |||||||||||||||||||||||||||||
| Primary | Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 29, 36, 43, 57, 71, 85, 99 and 113. | Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. One participant in the 0.3 mg/kg arm was not analyzed due to an atypical PK profile. | Posted | Median | Full Range | day | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. One participant in the 0.3 mg/kg arm was not analyzed due to an atypical PK profile. | Posted | Mean | Standard Deviation | ug/mL | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. One participant in the 0.3 mg/kg arm was not analyzed due to an atypical PK profile. | Posted | Mean | Standard Deviation | day*ug/mL | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. One participant in the 0.3 mg/kg arm was not analyzed due to an atypical PK profile. | Posted | Mean | Standard Deviation | Liters | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. One participant in the 0.3 mg/kg arm was not analyzed due to an atypical PK profile. | Posted | Mean | Standard Deviation | Liters/day | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Part 1 participants who received AIN457A at 0.3 mg/kg, 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. | Posted | Mean | Standard Deviation | day | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | Pharmacokinetics PK of AIN457: Tmax in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. | Posted | Median | Full Range | day | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | Pharmacokinetics PK of AIN457: Cmax in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. | Posted | Mean | Standard Error | ug/mL | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. | Posted | Mean | Standard Deviation | day*ug/mL | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | Pharmacokinetics PK of AIN457: Vz in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. | Posted | Mean | Standard Deviation | Liter | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | Pharmacokinetics PK of AIN457: CL in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. | Posted | Mean | Standard Deviation | Liters/day | Day 113 |
| ||||||||||||||||||||||||||||||
| Primary | Pharmacokinetics PK of AIN457: T1/2 in Parts 2 and 3 Participants | Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion. | Parts 2 and 3 participants who received AIN457A at 1 mg/kg, 3 mg/kg or 10 mg/kg were included in this analysis. | Posted | Mean | Standard Deviation | Day | Day 113 |
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70 | Clinical response to treatment was assessed according to ACR50 and ACR70 criteria. A participant was defined as an ACR50 or ACR70 responder if the following 3 conditions were met: 1) improvement of ≥50% or ≥ 70%, respectively, in the number of tender joints, 2) improvement of ≥50% or ≥ 70%, respectively, in the number of swollen joints and 3) improvement of ≥50% or ≥ 70%, respectively, in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant | The analysis was performed on the 10 mg and placebo treatment arms of the parts 2 and 3 participants. | Posted | Number | Percentage of participants | Day 43 |
|
| ||||||||||||||||||||||||||||||
| Secondary | Disease Activity Score (DAS28) of Parts 2 and 3 Participants | The DAS28 is a composite score based on tender and swollen joint counts, C reactive protein (CRP) concentrations, and the participant's global disease activity based on a visual analogue scale (VAS). The tender joint count (based on 28 joints) was calculated by scoring several different aspects of tenderness as assessed by pressure and joint manipulation on physical examination. The information on various types of tenderness was then collapsed into a single tender versus non-tender dichotomy, and the number of joints that were classified as tender was recorded. The swollen joint count was calculated in the same manner. For CRP concentrations, blood samples were collected and sent to a central laboratory for assessment. For the VAS assessment, the participant used a 100 mm horizontal VAS to assess the severity of his or her arthritis where 0 = none and 100 = most severe. DAS28 scores range from <2.6 (disease remission) to >5.1 (high disease activity). | The analysis was performed on the 10 mg and placebo treatment arms of the parts 2 and 3 participants. | Posted | Mean | Standard Error | scores on a scale | Day 43 |
|
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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 | Part 1 - AIN457A 0.3 mg/kg | AIN457A 0.3 mg/kg was administered intravenously as a single dose. | 1 | 6 | 3 | 6 | ||
| EG001 | Part 1 - AIN457A 1.0 mg/kg | AIN457A 1.0 mg/kg was administered intravenously as a single dose. | 0 | 6 | 2 | 6 | ||
| EG002 | Part 1 - AIN457A 3.0 mg/kg | AIN457A 3.0 mg/kg was administered intravenously as a single dose. | 1 | 6 | 5 | 6 | ||
| EG003 | Part 1 - AIN457A 10 mg/kg | AIN457A 10.0 mg/kg was administered intravenously as a single dose. | 0 | 6 | 2 | 6 | ||
| EG004 | Part 1 - Placebo | Placebo to AIN457A was administered intravenously as a single dose. | 0 | 8 | 4 | 8 | ||
| EG005 | Parts 2 and 3 - AIN457 1.0 mg/kg | AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. | 0 | 6 | 5 | 6 | ||
| EG006 | Parts 2 and 3 - AIN457 3.0 mg/kg | AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. | 1 | 6 | 4 | 6 | ||
| EG007 | Parts 2 and 3 - AIN457 10 mg/kg | AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. | 0 | 26 | 19 | 26 | ||
| EG008 | Parts 2 and 3 - Placebo | Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22. | 2 | 26 | 13 | 26 | ||
| EG009 | Part 1 - Healthy Volunteers - AIN457A 3 mg/kg | AIN457A 3.0 mg/kg was administered intravenously as a single dose. | 0 | 3 | 1 | 3 | ||
| EG010 | Part 1 - Healthy Volunteers - Placebo | Placebo to AIN457A was administered intravenously as a single dose. | 0 | 2 | 1 | 2 | ||
| EG011 | Part 1 - Healthy Volunteers - AIN457A 10 mg/kg | AIN457A 10 mg/kg was administered intravenously as a single dose. | 0 | 3 | 0 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Brachial plexopathy | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Endometrial hyperplasia | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Atrioventricular block first degree | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
| |
| Pain | General disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Excoriation | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Foot fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Ligament rupture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Traumatic haematoma | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Lumbar spinal stenosis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Carpal tunnel syndrome | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Postnasal drip | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Hypotension | Vascular 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 | 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
| Withdrawal by Subject |
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| Protocol Violation |
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| Male |
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AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
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| Part 1 - AIN457A 10 mg/kg |
AIN457A 10.0 mg/kg was administered intravenously as a single dose. |
|
|
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
|
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
|
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