Rheumatoid ArthritisPhase 1/2NCT00669942

Double Blind, Placebo-controlled, Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients

A Phase 1/2 study testing AIN457 in people with Rheumatoid Arthritis, run by Novartis Pharmaceuticals at 24 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: AIN457
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 104 participants
Where: 24 sitesin 6 countries
Study dates: Dec 2005to Nov 2008
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female patients with active rheumatoid arthritis in combination with a stable dose of methotrexate aged 18-75 years may participate in this trial.
Post menopausal or surgically sterile female patients are allowed. Women of child-bearing potential may participate if they are on a stable dose of methotrexate and if they are practicing effective contraception for at least 6 months prior to screening, willing to use 2 forms of contraception, including at least 1 barrier method during the study and for at least 2 months following the completion/discontinuation of the study.
Patients must have a diagnosis of active rheumatoid arthritis of stages I, II or III (ACR 1987 revised classification for criteria for RA). Disease duration of at least 6 months prior to randomization is essential;

Who cannot join

Current treatment with anti-TNF-α or anti IL-1 therapy (or other biological therapy).
Patients with congestive heart failure or poorly controlled diabetes mellitus (HbA1c value ≥10%).
Presence of any major chronic inflammatory autoimmune diseases like psoriasis, psoriatic arthritis, spondyloarthropathy, inflammatory bowel disease or SLE that can mimic rheumatoid arthritis diagnosis or that can interfere with efficacy evaluation in the study.
History of renal trauma, glomerulonephritis or patient with one kidney.
Pregnant or breastfeeding women will be excluded.
A positive tuberculin skin test.
Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

24 sites in 6 countries.

Country

City, postcode or hospital

24 sites in 6 countries

United States12 sites

Novartis Investigative Site
Anniston, Alabama, 36207-5710
Novartis Investigative Site
Bend, Oregon, 97701
Novartis Investigative Site
Duncansville, Pennsylvania, 16635
Novartis Investigative Site
Largo, Florida, 33773
Novartis Investigative Site
Madisonville, Kentucky, 42431
Novartis Investigative Site
Ocala, Florida, 34471
Novartis Investigative Site
Oklahoma City, Oklahoma, 73103
Novartis Investigative Site
Omaha, Nebraska, 68131-2197
Novartis Investigative Site
Palm Harbor, Florida, 34684
Novartis Investigative Site
Port Orange, Florida, 32127
Novartis Investigative Site
St Louis, Missouri, 63110
Novartis Investigative Site
Tucson, Arizona, 85724

Other trials in United States

Germany3 sites

Novartis Investigative Site
Bad Nauheim, 61231
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
München, 80336

Other trials in Germany

Spain3 sites

Novartis Investigative Site
A Coruña, Galicia, 15006
Novartis Investigative Site
Guadalajara, 19002
Novartis Investigative Site
Santiago de Compostela, Galicia, 15706

Other trials in Spain

Belgium2 sites

Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Merksem, 2170

Other trials in Belgium

Netherlands2 sites

Novartis Investigative Site
Amsterdam, 1105 AZ
Novartis Investigative Site
Nijmegen, 6525 GA

Other trials in Netherlands

Singapore2 sites

Novartis Investigative Site
Singapore, Singapore, 119074
Novartis Investigative Site
Singapore, Singapore, 529889

Other trials in Singapore

About this study

Official title: A Randomized, Double Blind, Placebo-controlled, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients With Pharmacodynamics Assessed in an Expanded Cohort at the Maximum Tolerated Dose

Conditions: Rheumatoid Arthritis
Being tested: AIN457, Placebo
Keywords: Rheumatoid Arthritis
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AIN457Biological
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
PlaceboDrug
Placebo to AIN457

Study groups in NCT00669942
Study group	Role	What they receive
Part 1 - AIN457A 0.3 mg/kg	Experimental	AIN457A 0.3 mg/kg was administered intravenously as a single dose. Receives: Biological: AIN457
Part 1 - AIN457A 1.0 mg/kg	Experimental	AIN457A 1.0 mg/kg was administered intravenously as a single dose. Receives: Biological: AIN457
Part 1 - AIN457A 3.0 mg/kg	Experimental	AIN457A 3.0 mg/kg was administered intravenously as a single dose. Receives: Biological: AIN457
Part 1 - AIN457A 10 mg/kg	Experimental	AIN457A 10.0 mg/kg was administered intravenously as a single dose. Receives: Biological: AIN457
Part 1 - Placebo	Placebo comparator	Placebo to AIN457A was administered intravenously as a single dose. Receives: Drug: Placebo
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. Receives: Biological: AIN457
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. Receives: Biological: AIN457
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. Receives: Biological: AIN457
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. Receives: Drug: Placebo
Part 1 - Healthy Volunteers - AIN457A 3 mg/kg	Experimental	AIN457A 3.0 mg/kg was administered intravenously as a single dose. Receives: Biological: AIN457
Part 1 - Healthy Volunteers - AIN457A 10 mg/kg	Experimental	AIN457A 10 mg/kg was administered intravenously as a single dose. Receives: Biological: AIN457
Part 1 - Healthy Volunteers - Placebo	Placebo comparator	Placebo to AIN457A was administered intravenously as a single dose. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 113
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 113

Secondary outcomes (2)

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
Measured: 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).
Measured: Day 43

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2005Nov 2008

First posted1 May 2008 (estimated)
Study startDec 2005
Primary completionNov 2008
Study completionNov 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 104 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00669942
Sponsor's protocol ID: CAIN457A2101
Status last verified: Mar 2015
First submitted: 29 Apr 2008
Last updated: 30 Mar 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 20926833

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Rheumatoid Arthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double Blind, Placebo-controlled, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients With Pharmacodynamics Assessed in an Expanded Cohort at the Maximum Tolerated Dose
ClinicalTrials.gov ID: NCT00669942
Acronym / sponsor ID: CAIN457A2101
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 104 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Dec 2005
Primary completion: Nov 2008 (actual)
Study completion: Nov 2008 (actual)
First posted: 1 May 2008 (estimated)
Results: Posted 30 Mar 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, care provider)
Number of arms: 12

Arm	Type	Receives
Part 1 - AIN457A 0.3 mg/kg	Experimental	Biological: AIN457AIN457A 0.3 mg/kg was administered intravenously as a single dose.
Part 1 - AIN457A 1.0 mg/kg	Experimental	Biological: AIN457AIN457A 1.0 mg/kg was administered intravenously as a single dose.
Part 1 - AIN457A 3.0 mg/kg	Experimental	Biological: AIN457AIN457A 3.0 mg/kg was administered intravenously as a single dose.
Part 1 - AIN457A 10 mg/kg	Experimental	Biological: AIN457AIN457A 10.0 mg/kg was administered intravenously as a single dose.
Part 1 - Placebo	Placebo comparator	Drug: PlaceboPlacebo to AIN457A was administered intravenously as a single dose.
Parts 2 and 3 - AIN457A 1.0 mg/kg	Experimental	Biological: AIN457AIN457A 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.
Parts 2 and 3 - AIN457A 3.0 mg/kg	Experimental	Biological: AIN457AIN457A 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	Biological: AIN457AIN457A 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	Drug: PlaceboPlacebo 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	Biological: AIN457AIN457A 3.0 mg/kg was administered intravenously as a single dose.
Part 1 - Healthy Volunteers - AIN457A 10 mg/kg	Experimental	Biological: AIN457AIN457A 10 mg/kg was administered intravenously as a single dose.
Part 1 - Healthy Volunteers - Placebo	Placebo comparator	Drug: PlaceboPlacebo to AIN457A was administered intravenously as a single dose.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Male and female patients with active rheumatoid arthritis in combination with a stable dose of methotrexate aged 18-75 years may participate in this trial.
Post menopausal or surgically sterile female patients are allowed. Women of child-bearing potential may participate if they are on a stable dose of methotrexate and if they are practicing effective contraception for at least 6 months prior to screening, willing to use 2 forms of contraception, including at least 1 barrier method during the study and for at least 2 months following the completion/discontinuation of the study.
Patients must have a diagnosis of active rheumatoid arthritis of stages I, II or III (ACR 1987 revised classification for criteria for RA). Disease duration of at least 6 months prior to randomization is essential;

Key exclusion criteria (7 listed)

Current treatment with anti-TNF-α or anti IL-1 therapy (or other biological therapy).
Patients with congestive heart failure or poorly controlled diabetes mellitus (HbA1c value ≥10%).
Presence of any major chronic inflammatory autoimmune diseases like psoriasis, psoriatic arthritis, spondyloarthropathy, inflammatory bowel disease or SLE that can mimic rheumatoid arthritis diagnosis or that can interfere with efficacy evaluation in the study.
History of renal trauma, glomerulonephritis or patient with one kidney.
Pregnant or breastfeeding women will be excluded.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AIN457AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.	Biological	Part 1 - AIN457A 0.3 mg/kg, Part 1 - AIN457A 1.0 mg/kg, Part 1 - AIN457A 10 mg/kg, Part 1 - AIN457A 3.0 mg/kg, Part 1 - Healthy Volunteers - AIN457A 10 mg/kg, Part 1 - Healthy Volunteers - AIN457A 3 mg/kg, Parts 2 and 3 - AIN457A 1.0 mg/kg, Parts 2 and 3 - AIN457A 10 mg/kg, Parts 2 and 3 - AIN457A 3.0 mg/kg
PlaceboPlacebo to AIN457	Drug	Part 1 - Healthy Volunteers - Placebo, Part 1 - Placebo, Parts 2 and 3 - Placebo

Primary outcome

Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20)
Time frame: Day 43
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.
Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants
Time frame: Day 113
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.
PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants
Time frame: Day 113
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.
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
Time frame: Day 113
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.
PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 Participants
Time frame: Day 113
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.
PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 Participants
Time frame: Day 113
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.
PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 Participants
Time frame: Day 113
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.
Pharmacokinetics PK of AIN457: Tmax in Parts 2 and 3 Participants
Time frame: Day 113
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.
Pharmacokinetics PK of AIN457: Cmax in Parts 2 and 3 Participants
Time frame: Day 113
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.
Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants
Time frame: Day 113
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.
Pharmacokinetics PK of AIN457: Vz in Parts 2 and 3 Participants
Time frame: Day 113
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.
Pharmacokinetics PK of AIN457: CL in Parts 2 and 3 Participants
Time frame: Day 113
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.
Pharmacokinetics PK of AIN457: T1/2 in Parts 2 and 3 Participants
Time frame: Day 113
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.

2 secondary outcomes

Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70
Time frame: Day 43
Disease Activity Score (DAS28) of Parts 2 and 3 Participants
Time frame: Day 43

Results and safety

Results posted to the registry on 30 Mar 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1 - AIN457A 0.3 mg/kg	6	6
Part 1 - AIN457A 1.0 mg/kg	6	6
Part 1 - AIN457A 3.0 mg/kg	6	6
Part 1 - AIN457A 10 mg/kg	6	6
Part 1 - Placebo	8	8
Parts 2 and 3 - AIN457A 1.0 mg/kg	0	0
Parts 2 and 3 - AIN457A 3.0 mg/kg	0	0
Parts 2 and 3 - AIN457A 10 mg/kg	0	0
Parts 2 and 3 - Placebo	0	0
Part 1 - Healthy Volunteers - AIN457A 3 mg/kg	0	0
Part 1 - Healthy Volunteers - AIN457A 10 mg/kg	0	0
Part 1 - Healthy Volunteers - Placebo	0	0

Primary outcome: Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20)

Time frame: Day 43. Number. Unit: percentage of participants

Measure	Parts 2 and 3 - AIN457A 10 mg/kg n = 26	Parts 2 and 3 - Placebo n = 26
Value	46	27

Population analysed: The analysis was performed on the 10 mg and placebo treatment arms of the parts 2 and 3 participants.

Primary outcome: Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants

Time frame: Day 113. Median (Full Range). Unit: day

Measure	Part 1 - AIN457A 0.3 mg/kg n = 5	Part 1 - AIN457A 1.0 mg/kg n = 6	Part 1 - AIN457A 3.0 mg/kg n = 6	Part 1 - AIN457A 10 mg/kg n = 6
Value	0.09028 (0.0833 to 0.167)	0.08472 (0.0813 to 0.167)	0.1253 (0.0806 to 0.167)	0.1260 (0.0833 to 0.990)

Population analysed: 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.

Primary outcome: PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants

Time frame: Day 113. Mean (Standard Deviation). Unit: ug/mL

Measure	Part 1 - AIN457A 0.3 mg/kg n = 5	Part 1 - AIN457A 1.0 mg/kg n = 6	Part 1 - AIN457A 3.0 mg/kg n = 6	Part 1 - AIN457A 10 mg/kg n = 6
Value	8.772 (1.8020)	35.22 (18.755)	70.95 (9.9472)	211.8 (36.837)

Primary outcome: 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

Time frame: Day 113. Mean (Standard Deviation). Unit: day*ug/mL

Measure	Part 1 - AIN457A 0.3 mg/kg n = 5	Part 1 - AIN457A 1.0 mg/kg n = 6	Part 1 - AIN457A 3.0 mg/kg n = 6	Part 1 - AIN457A 10 mg/kg n = 6
AUCinf	141.3 (48.781)	430.7 (48.281)	1148 (330.89)	4080 (768.87)
AUClast	132.7 (42.824)	415.6 (42.793)	1097 (291.59)	3936 (697.65)

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1 - AIN457A 0.3 mg/kg	1 of 6 (16.7%)	3 of 6 (50%)	Not reported
Part 1 - AIN457A 1.0 mg/kg	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Part 1 - AIN457A 3.0 mg/kg	1 of 6 (16.7%)	5 of 6 (83.3%)	Not reported
Part 1 - AIN457A 10 mg/kg	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Part 1 - Placebo	0 of 8 (0%)	4 of 8 (50%)	Not reported
Parts 2 and 3 - AIN457 1.0 mg/kg	0 of 6 (0%)	5 of 6 (83.3%)	Not reported
Parts 2 and 3 - AIN457 3.0 mg/kg	1 of 6 (16.7%)	4 of 6 (66.7%)	Not reported
Parts 2 and 3 - AIN457 10 mg/kg	0 of 26 (0%)	19 of 26 (73.1%)	Not reported
Parts 2 and 3 - Placebo	2 of 26 (7.7%)	13 of 26 (50%)	Not reported
Part 1 - Healthy Volunteers - AIN457A 3 mg/kg	0 of 3 (0%)	1 of 3 (33.3%)	Not reported
Part 1 - Healthy Volunteers - Placebo	0 of 2 (0%)	1 of 2 (50%)	Not reported
Part 1 - Healthy Volunteers - AIN457A 10 mg/kg	0 of 3 (0%)	0 of 3 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 20926833Hueber 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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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

Novartis principal investigator

Novartis investigator site

24 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AIN457 in people with Rheumatoid Arthritis, run by Novartis Pharmaceuticals at 24 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Germany, Spain, Belgium, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20) (time frame: Day 43). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00669942, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2015.