Efficacy and Safety of AIN457 (Secukinumab) in Patients With Relapsing Multiple Sclerosis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01874340
• Collaborator: (none)
• Enrollment: 28
• Locations: 13
• Arms: 4
• Duration (Months): 10
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of AIN457 versus placebo in patients with relapsing multiple sclerosis.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Placebo; Drug: AIN457	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Adaptive Dose-ranging Study to Evaluate the Efficacy and Safety of AIN457 (Secukinumab) in Patients With Relapsing Multiple Sclerosis
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AIN457 low dose AIN457 will be administered intravenously. Approximately 65 patients will be randomized to AIN457 low dose in Stage 1. An additional 40 patients may be randomized to this group if it is one of the two selected dose groups to be expanded for Stage 2 following an Interim Analysis.	Drug: AIN457; AIN457 will be administered at predefined visits over the 6-month treatment phase.
Placebo Comparator: Placebo Matching placebo will be administered intravenously. Approximately 105 patients will be randomized to placebo (65 in Stage 1 and 40 in Stage 2).	Drug: Placebo; Placebo will be administered at predefined visits over the 6-month treatment phase.
Experimental: AIN457 middle dose AIN457 will be administered intravenously. Approximately 65 patients will be randomized to AIN457 middle dose in Stage 1. An additional 40 patients may be randomized to this group if it is one of the two selected dose groups to be expanded for Stage 2 following an Interim Analysis	Drug: AIN457; AIN457 will be administered at predefined visits over the 6-month treatment phase.
Experimental: AIN457 high dose AIN457 will be administered intravenously. Approximately 65 patients will be randomized to AIN457 high dose in Stage 1. An additional 40 patients may be randomized to this group if it is one of the two selected dose groups to be expanded for Stage 2 following an Interim Analysis.	Drug: AIN457; AIN457 will be administered at predefined visits over the 6-month treatment phase.

Outcome Measures

Primary Outcome Measures

1. Cumulative Number of New Gadolinium [Gd]-Enhancing T1-weighted Lesions [Months 3, 4, 5, 6]

   Due to early termination this trial was not powered for efficacy no statistical analysis was performed

Secondary Outcome Measures

1. Annualized Relapse Rate [6 Months]

   Due to early termination this trial was not powered for efficacy no statistical analysis was performed

2. Combined Unique Active Lesions (CUAL) [Months 3, 4, 5, 6]

   Due to early termination this trial was not powered for efficacy no statistical analysis was performed

3. Change in Total Volume of T2-weighted Lesions [Baseline, Month 6]

   Due to early termination this trial was not powered for efficacy no statistical analysis was performed

4. Number of Particpants With Adverse Events as a Measure of Safety and Tolerability [6 months]

   Number of particpants with Adverse events as a measure of safety and tolerability

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of Multiple Sclerosis according to 2010 revised McDonald criteria

• Disease duration of 10 years or less

• At least one relapse in the last year

• EDSS score 0 to 5.0 at entry

Exclusion Criteria:

• Active chronic disease of the immune system other than multiple sclerosis

• History of malignancy within the past 5 years

• Active systemic bacterial, viral or fungal infections

• Previous treatment with more than one class of multiple sclerosis therapies except for previous treatment with glatiramer acetate and interferon-beta(s)

• Any medically unstable condition

• Unable to undergo MRI scans or repeated blood tests

• Pregnant or nursing females

• Women of child-bearing potential must use reliable forms of contraception

• Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Brugge		Belgium	8000
2	Novartis Investigative Site	JIhlava		Czech Republic	586 33
3	Novartis Investigative Site	St Herblain		France	44800
4	Novartis Investigative Site	Roma	RM	Italy	00133
5	Novartis Investigative Site	Osaka-city	Osaka	Japan	556-0016
6	Novartis Investigative Site	Lodz		Poland	93-121
7	Novartis Investigative Site	Poznan		Poland	60-355
8	Novartis Investigative Site	Moscow		Russian Federation	127018
9	Novartis Investigative Site	Saint-Petersburg		Russian Federation	194044
10	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
11	Novartis Investigative Site	Bilbao	Pais Vasco	Spain	48013
12	Novartis Investigative Site	Stockholm		Sweden	17176
13	Novartis Investigative Site	Atakum / Samsun		Turkey	55139

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: NCT01874340
• Other Study ID Numbers: CAIN457B2203; 2012-004019-29
• First Posted: Jun 11, 2013
• Last Update Posted: Jun 1, 2015
• Last Verified: May 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Multiple Sclerosis; Relapsing Multiple Sclerosis; AIN457; Secukinumab; Magnetic Resonance Imaging; Relapsing Remitting Multiple Sclerosis; Autoimmune Diseases; Nervous System Diseases; Immune System Diseases; Demyelinating Diseases
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis

Study Results

Participant Flow

Arm/Group Title	AIN457 15 mg/kg	AIN457 7 mg/kg	AIN457 3 mg/kg	Placebo
Arm/Group Description	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	Matching placebo will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.
Period Title: Overall Study
STARTED	6	8	8	6
COMPLETED	0	0	0	1
NOT COMPLETED	6	8	8	5

Baseline Characteristics

Arm/Group Title	AIN457 15 mg/kg	AIN457 7 mg/kg	AIN457 3 mg/kg	Placebo	Total
Arm/Group Description	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	Matching placebo will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	Total of all reporting groups
Overall Participants	6	8	8	6	28
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	28.8 (7.73)	34.5 (8.64)	35.5 (9.71)	34.0 (9.30)	33.5 (8.79)
Sex: Female, Male (Count of Participants)
Female	4 66.7%	4 50%	6 75%	4 66.7%	18 64.3%
Male	2 33.3%	4 50%	2 25%	2 33.3%	10 35.7%

Outcome Measures

1. Primary Outcome

Title	Cumulative Number of New Gadolinium [Gd]-Enhancing T1-weighted Lesions
Description	Due to early termination this trial was not powered for efficacy no statistical analysis was performed
Time Frame	Months 3, 4, 5, 6

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study and just one patient completing treatment as planned, no statistical analyses could be performed for the efficacy endpoints defined in the protocol.

Arm/Group Title	AIN457 15 mg/kg	AIN457 7 mg/kg	AIN457 3 mg/kg	Placebo
Arm/Group Description	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	Matching placebo will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.
Measure Participants	0	0	0	0

2. Secondary Outcome

Title	Annualized Relapse Rate
Description	Due to early termination this trial was not powered for efficacy no statistical analysis was performed
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study and just one patient completing treatment as planned, no statistical analyses could be performed for the efficacy endpoints defined in the protocol.

Arm/Group Title	AIN457 15 mg/kg	AIN457 7 mg/kg	AIN457 3 mg/kg	Placebo
Arm/Group Description	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	Matching placebo will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.
Measure Participants	0	0	0	0

3. Secondary Outcome

Title	Combined Unique Active Lesions (CUAL)
Description	Due to early termination this trial was not powered for efficacy no statistical analysis was performed
Time Frame	Months 3, 4, 5, 6

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study and just one patient completing treatment as planned, no statistical analyses could be performed for the efficacy endpoints defined in the protocol.

Arm/Group Title	AIN457 15 mg/kg	AIN457 7 mg/kg	AIN457 3 mg/kg	Placebo
Arm/Group Description	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	Matching placebo will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.
Measure Participants	0	0	0	0

4. Secondary Outcome

Title	Change in Total Volume of T2-weighted Lesions
Description	Due to early termination this trial was not powered for efficacy no statistical analysis was performed
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

Due to the early termination of the study and just one patient completing treatment as planned, no statistical analyses could be performed for the efficacy endpoints defined in the protocol.

Arm/Group Title	AIN457 15 mg/kg	AIN457 7 mg/kg	AIN457 3 mg/kg	Placebo
Arm/Group Description	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	Matching placebo will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.
Measure Participants	0	0	0	0

5. Secondary Outcome

Title	Number of Particpants With Adverse Events as a Measure of Safety and Tolerability
Description	Number of particpants with Adverse events as a measure of safety and tolerability
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The safety set consists of all subjects who received at least one dose of study medication. Subjects will be analyzed according to the treatment received.

Arm/Group Title	AIN457 15 mg/kg	AIN457 7 mg/kg	AIN457 3 mg/kg	Placebo
Arm/Group Description	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.	Matching placebo will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.
Measure Participants	6	8	8	6
Adverse Events (AE)	1 16.7%	3 37.5%	3 37.5%	2 33.3%
Death	0 0%	0 0%	0 0%	0 0%
Non-Fatal Seriuos Aderse Event (SAE)	0 0%	1 12.5%	0 0%	0 0%

Adverse Events

Adverse Event Reporting Description	The safety set consists of all subjects who received at least one dose of study medication. Subjects were analyzed according to the treatment received.
Arm/Group Title	AIN457 15 mg/kg		AIN457 7 mg/kg		AIN457 3 mg/kg		Placebo
Arm/Group Description	AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.		AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.		AIN457 will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.		Matching placebo will be administered intravenously at day1, Week 2, week 4 and every 4 weeks therafter.
All Cause Mortality
	AIN457 15 mg/kg		AIN457 7 mg/kg		AIN457 3 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	AIN457 15 mg/kg		AIN457 7 mg/kg		AIN457 3 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Gastrointestinal disorders
Gastritis	0/6 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	AIN457 15 mg/kg		AIN457 7 mg/kg		AIN457 3 mg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		3/8 (37.5%)		3/8 (37.5%)		2/6 (33.3%)
Gastrointestinal disorders
Nausea	0/6 (0%)		0/8 (0%)		0/8 (0%)		1/6 (16.7%)
General disorders
Pyrexia	0/6 (0%)		0/8 (0%)		0/8 (0%)		1/6 (16.7%)
Infections and infestations
Nasopharyngitis	1/6 (16.7%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Bronchitis	0/6 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Pharyngitis	0/6 (0%)		0/8 (0%)		0/8 (0%)		1/6 (16.7%)
Tinea versicolour	0/6 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Vaginal infection	0/6 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)
Investigations
C-reactive protein increased	0/6 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
White blood cell count increased	0/6 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Metabolism and nutrition disorders
Hyperphagia	0/6 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/6 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Back pain	0/6 (0%)		1/8 (12.5%)		0/8 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Rash	0/6 (0%)		0/8 (0%)		1/8 (12.5%)		0/6 (0%)

Limitations/Caveats

Due to early termination this trial was not powered for efficacy no statistical analysis was performed

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 doesn 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 the trial results in their entirety.