A Study Comparing AIN457 to Placebo in Subjects With a Diagnosis of Moderate to Severe Stable Plaque Psoriasis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00669916
• Collaborator: (none)
• Enrollment: 36
• Arms: 2
• Duration (Months): 9

Study Details

Study Description

Brief Summary

This is a two-arm, parallel group, double-blind, placebo-controlled proof-of-concept study comparing 3 mg/kg of AIN457 to placebo. Subjects with a diagnosis of moderate to severe stable plaque psoriasis will be randomized to receive either AIN457 or placebo. AIN457 or placebo will be administered by single infusion at baseline and subjects will be observed for up to 26 weeks following the infusion.

Condition or Disease	Intervention/Treatment	Phase
Plaque Psoriasis	Biological: AIN457; Drug: Placebo	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Basic Science
• Official Title: Phase 2a Single-Dose, Randomized, Double Blind, Multi-Center, Parallel-Group, Placebo-Controlled Proof of Concept Study to Assess the Efficacy, Safety, Tolerability, and Population Pharmacokinetics of AIN457 in Patients With Stable Plaque-type Psoriasis
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Nov 1, 2007
• Actual Study Completion Date: Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AIN457 AIN457A 3mg/kg was administered intravenously as a single dose.	Biological: AIN457; single infusion of 3 mg/kg
Placebo Comparator: Placebo Placebo was administered intravenously as a single dose.	Drug: Placebo; single infusion of placebo

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Mean Score [Baseline, Week 4]

   The PASI assessed the extent of psoriasis on four body surface areas (head, trunk and upper limbs) and the degree of plaque erythema, scaling and thickness. The PASI score accounted for the extent of body surface area affected by the erythema, scaling and thickness and the severity of these measures. The score ranged from 0 (no disease) to 72 (maximal disease) where a reduction in PASI score from baseline indicates improvement. The percentage change was calculated by subtracting the week 4 values from the baseline values.The percentage change was calculated for each entire treatment group (not for each participant). A positive percentage change from baseline indicates improvement.

2. Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score [Baseline, Week 4]

   The IGA is an instrument which captured and categorized the global assessment of all clinical signs and symptoms of disease. The investigator used all available information for the assessment, including subjective information from the participant and (where available) photographs taken at baseline. The IGA categories were clear, almost clear, mild disease, moderate disease, severe disease and very severe disease. This outcome measure shows the percentage of patients who experienced a category change from baseline. Category changes of 1, 2 or 3 indicate improvement.

Secondary Outcome Measures

1. Pharmacokinetics of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) [Day 182]

   Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.

2. Pharmacokinetics of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) [Day 182]

   Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.

3. Pharmacokinetics 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) [Day 182]

   Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.

4. Pharmacokinetics of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) [Day 182]

   Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.

5. Pharmacokinetics of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) [Day 182]

   Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.

6. Pharmacokinetics of AIN457: Terminal Elimination Half-life (T1/2) [Day 182]

   Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or females, aged 18-69 at time of consent.

• Post menopausal or surgically sterile female patients are allowed. Male patients must be willing to use contraception method at least for 3 months following the completion of the study. Women of child-bearing potential will not be allowed to participate.

• Diagnosis of plaque psoriasis for at least 6 months prior to screening. The patients must meet both of the following criterion:

1. Coverage of the body surface area (BSA) of 10% or more with plaques

2. A score of 3 or more on the IGA scale

• Stable plaque psoriasis at screening and randomization.

• PASI score of 12 or greater at randomization.

• Able to communicate well with the investigator, and to understand and comply with the requirements of the study. Understand and sign the written informed consent.

• Patients must have normal laboratory values for screening laboratory test results of hematological (hemoglobin, WBCs, neutrophils, platelets) and renal (serum creatinine) assessments. For the transaminases, aspartate aminotransferase and alanine aminotransferase, levels 1.5 times the upper limit of normal will be accepted. For the additional hepatic laboratory results (alkaline phosphatase, gamma-glutamyltransferase, bilirubin), patients must have non-clinically significant values.

Exclusion Criteria:

• Currently have any of the nonplaque forms of psoriasis: erythrodermic, guttate, or pustular.

• Currently have drug-induced psoriasis (new onset or exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium).

• Men who are planning to initiate a pregnancy while enrolled in the study or for 3 months following completion of the study.

• Women of child-bearing potential are not allowed in the study.

• Used any investigational drug within the previous 4 weeks.

• Recent previous treatment with anti-TNF-α therapy (or other biological therapy), immunosuppressive agents such as cyclosporine, mycophenolate, pimecrolimus, or tacrolimus. The following washout period will be required for such patients to be eligible to participate in the trial.

1. 2 months washout prior to screening for etanercept, adalimumab, or infliximab.

2. 1 month washout prior to screening for cyclosporine, mycophenolate, tacrolimus, and any systemic immunosuppressants including, but not limited to, methotrexate, azathioprine, 6-thioguanine, mercaptopurine, and hydroxyurea

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00669916
• Other Study ID Numbers: CAIN457A2102
• First Posted: May 1, 2008
• Last Update Posted: Apr 10, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Plaque psoriasis
• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

Arm/Group Title	AIN457	Placebo
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.	Placebo was administered intravenously as a single dose.
Period Title: Overall Study
STARTED	18	18
COMPLETED	18	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	AIN457	Placebo	Total
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.	Placebo was administered intravenously as a single dose.	Total of all reporting groups
Overall Participants	18	18	36
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	50.7 (8.73)	50.9 (12.04)	50.8 (10.37)
Sex: Female, Male (Count of Participants)
Female	11 61.1%	13 72.2%	24 66.7%
Male	7 38.9%	5 27.8%	12 33.3%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Mean Score
Description	The PASI assessed the extent of psoriasis on four body surface areas (head, trunk and upper limbs) and the degree of plaque erythema, scaling and thickness. The PASI score accounted for the extent of body surface area affected by the erythema, scaling and thickness and the severity of these measures. The score ranged from 0 (no disease) to 72 (maximal disease) where a reduction in PASI score from baseline indicates improvement. The percentage change was calculated by subtracting the week 4 values from the baseline values.The percentage change was calculated for each entire treatment group (not for each participant). A positive percentage change from baseline indicates improvement.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	AIN457	Placebo
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.	Placebo was administered intravenously as a single dose.
Measure Participants	18	18
Number [Percentage change in PASI mean score]	58	4

2. Secondary Outcome

Title	Pharmacokinetics of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Description	Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time Frame	Day 182

Outcome Measure Data

Analysis Population Description

The population included all AIN457 treatment group participants except for two participants who had a nontypical PK profile for Tmax, Cmax, CI and Vz.

Arm/Group Title	AIN457
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.
Measure Participants	16
Median (Full Range) [days]	0.11

3. Secondary Outcome

Title	Pharmacokinetics of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax)
Description	Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time Frame	Day 182

Outcome Measure Data

Analysis Population Description

The population included all AIN457A treatment group participants except for two participants who had a nontypical PK profile for Tmax, Cmax, CI and Vz.

Arm/Group Title	AIN457
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.
Measure Participants	16
Mean (Standard Deviation) [ug/mL]	74.5 (13.1)

4. Secondary Outcome

Title	Pharmacokinetics 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)
Description	Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time Frame	Day 182

Outcome Measure Data

Analysis Population Description

All AIN457A treatment group participants

Arm/Group Title	AIN457
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.
Measure Participants	18
AUClast	1532 (343)
AUCinf	1629 (361)

5. Secondary Outcome

Title	Pharmacokinetics of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz)
Description	Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time Frame	Day 182

Outcome Measure Data

Analysis Population Description

The population included all AIN457A treatment group participants except for two participants who had a nontypical PK profile for Tmax, Cmax, CI and Vz.

Arm/Group Title	AIN457
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.
Measure Participants	16
Mean (Standard Error) [Liters]	7.31 (1.72)

6. Secondary Outcome

Title	Pharmacokinetics of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL)
Description	Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time Frame	Day 182

Outcome Measure Data

Analysis Population Description

The population included all AIN457A treatment group participants except for two participants who had a nontypical PK profile for Tmax, Cmax, CI and Vz.

Arm/Group Title	AIN457
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.
Measure Participants	16
Mean (Standard Deviation) [Liters/day]	0.18 (0.05)

7. Primary Outcome

Title	Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score
Description	The IGA is an instrument which captured and categorized the global assessment of all clinical signs and symptoms of disease. The investigator used all available information for the assessment, including subjective information from the participant and (where available) photographs taken at baseline. The IGA categories were clear, almost clear, mild disease, moderate disease, severe disease and very severe disease. This outcome measure shows the percentage of patients who experienced a category change from baseline. Category changes of 1, 2 or 3 indicate improvement.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	AIN457	Placebo
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.	Placebo was administered intravenously as a single dose.
Measure Participants	18	18
Change in IGA score = -1	5.6 31.1%	11.1 61.7%
Change in IGA score = 0	11.1 61.7%	77.8 432.2%
Change in IGA score = 1	33.3 185%	11.1 61.7%
Change in IGA score = 2	44.4 246.7%	0 0%
Change in IGA score = 3	5.6 31.1%	0 0%

8. Secondary Outcome

Title	Pharmacokinetics of AIN457: Terminal Elimination Half-life (T1/2)
Description	Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Time Frame	Day 182

Outcome Measure Data

Analysis Population Description

All AIN457A treatment group participants

Arm/Group Title	AIN457
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.
Measure Participants	18
Mean (Standard Deviation) [day]	29.2 (6.4)

Adverse Events

Arm/Group Title	AIN457A		Placebo
Arm/Group Description	AIN457A 3mg/kg was administered intravenously as a single dose.		Placebo was administered intravenously as a single dose.
All Cause Mortality
	AIN457A		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AIN457A		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/18 (5.6%)		0/18 (0%)
Cardiac disorders
Cardiac failure congestive	1/18 (5.6%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	AIN457A		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/18 (50%)		8/18 (44.4%)
Eye disorders
Corneal degeneration	0/18 (0%)		1/18 (5.6%)
Gastrointestinal disorders
Abdominal distension	0/18 (0%)		1/18 (5.6%)
Nausea	1/18 (5.6%)		0/18 (0%)
General disorders
Fatigue	2/18 (11.1%)		1/18 (5.6%)
Oedema peripheral	1/18 (5.6%)		0/18 (0%)
Infections and infestations
Fungal infection	1/18 (5.6%)		0/18 (0%)
Gastroenteritis viral	0/18 (0%)		1/18 (5.6%)
Influenza	1/18 (5.6%)		0/18 (0%)
Injection site infection	1/18 (5.6%)		0/18 (0%)
Peritonsillar abscess	1/18 (5.6%)		0/18 (0%)
Pneumonia	0/18 (0%)		1/18 (5.6%)
Sinusitis	1/18 (5.6%)		1/18 (5.6%)
Tonsillitis	1/18 (5.6%)		0/18 (0%)
Upper respiratory tract infection	0/18 (0%)		1/18 (5.6%)
Investigations
Alanine aminotransferase increased	1/18 (5.6%)		0/18 (0%)
Aspartate aminotransferase increased	1/18 (5.6%)		0/18 (0%)
Blood alkaline phosphatase increased	1/18 (5.6%)		0/18 (0%)
Blood cholesterol increased	2/18 (11.1%)		0/18 (0%)
Blood creatine phosphokinase increased	0/18 (0%)		1/18 (5.6%)
Blood glucose increased	2/18 (11.1%)		1/18 (5.6%)
Blood ketone body increased	1/18 (5.6%)		0/18 (0%)
Blood triglycerides increased	2/18 (11.1%)		2/18 (11.1%)
Glucose urine present	1/18 (5.6%)		0/18 (0%)
Lipase increased	0/18 (0%)		1/18 (5.6%)
Protein urine present	1/18 (5.6%)		1/18 (5.6%)
Metabolism and nutrition disorders
Hypercholesterolaemia	1/18 (5.6%)		0/18 (0%)
Hyperlipidaemia	1/18 (5.6%)		0/18 (0%)
Musculoskeletal and connective tissue disorders
Neck pain	0/18 (0%)		1/18 (5.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm	0/18 (0%)		1/18 (5.6%)
Nervous system disorders
Headache	1/18 (5.6%)		1/18 (5.6%)
Renal and urinary disorders
Nephrolithiasis	1/18 (5.6%)		0/18 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/18 (5.6%)		0/18 (0%)
Skin and subcutaneous tissue disorders
Drug eruption	1/18 (5.6%)		0/18 (0%)
Pruritus	1/18 (5.6%)		0/18 (0%)
Rash	1/18 (5.6%)		0/18 (0%)
Skin exfoliation	1/18 (5.6%)		0/18 (0%)
Skin fissures	1/18 (5.6%)		0/18 (0%)
Skin maceration	1/18 (5.6%)		0/18 (0%)
Surgical and medical procedures
Cataract operation	0/18 (0%)		1/18 (5.6%)
Vascular disorders
Hypertension	2/18 (11.1%)		1/18 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.