ATX-MS-1467 in Patients With Relapsing Forms of Multiple Sclerosis

• Sponsor: Apitope Technology (Bristol) Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01097668
• Collaborator: Aptiv Solutions (Industry), ClinStar, LLC (Industry)
• Enrollment: 43
• Locations: 16
• Arms: 2
• Duration (Months): 40
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Phase 1 study to assess the safety and biological activity of ATX-MS-1467 in patients with relapsing forms of multiple sclerosis. This will be an open label upward dose titration involving injections on 9 occasions, each two weeks apart. After dosing is complete there will be a 22 week follow up period. Blood samples will be drawn throughout the study to monitor safety and the body's response to the injections and MRI scans will be performed on several occasions to follow the course of the multiple sclerosis during the trial.

Condition or Disease	Intervention/Treatment	Phase
Relapsing Remitting Multiple Sclerosis	Biological: ATX-MS-1467	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: SAFETY AND PROOF OF PRINCIPLE STUDY OF ATX-MS-1467 IN PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS: OPEN LABEL UPWARD TITRATION OVER FIVE DOSE LEVELS AND USING TWO ROUTES OF ADMINISTRATION (INTRADERMAL AND SUBCUTANEOUS).
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intradermal injection Injections will be given by the intradermal route	Biological: ATX-MS-1467; Disease specific immune modulating treatment for multiple sclerosis
Experimental: Subcutaneous injection Injections will be given by the subcutaneous route	Biological: ATX-MS-1467; Disease specific immune modulating treatment for multiple sclerosis

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability [48 weeks]

   Occurrence of treatment emergent Adverse Events (AE), Serious Adverse Events, and laboratory abnormalities up to week 48 compared to baseline.

Secondary Outcome Measures

1. The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI). [16 and 20 weeks]

   Number of new or persisting Gadolinium-enhancing lesions at week 16 and 20 when compared to baseline.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 1. Patients who have definite relapsing multiple sclerosis disease as defined by the McDonald criteria (McDonald et al., 2001 and 2005) and as assessed by a neurologist.

1. HLA DRB1*15 positive.

2. High baseline levels of T-cell proliferation in response to myelin basic protein, defined as >1000 cpm with a >3 stimulation index compared to background.

3. Disease duration equal to or less than 10 years (from the first clinical event).

4. At least one documented relapse in the previous 12 months or two relapses within the previous 24 months prior to screening.

5. Must be in a clinically stable or improving neurological state during the 28 days preceding Screening.

6. EDSS score < 5.5.

Exclusion Criteria:

• 1. Subjects treated with β-interferon, plasma exchange, intravenous gamma globulin within the 3 months prior to Study Day 1 2. Subjects treated with glatiramer acetate at any time in the past 3. Subjects who have been treated with parenteral steroids or adrenocorticotropic hormone within 3 months days prior to Study Day 1 4. Prior treatment with: cytotoxic agents (including but not limited to cladribine, mitoxantrone, cyclophosphamide, azathioprine, methotrexate), fingolimod, laquinimod, teriflunomide, total lymphoid irradiation, stem cell or bone marrow transplantation, or monoclonal antibody therapy (including natalizumab, daclizumab, alemtuzumab) 5. Prior use of disease related T-cell vaccine or peptide-tolerising agent to treat MS 6. Use of any investigational drug or experimental procedure within 6 months prior to Study Day 1 including cytokine or anti-cytokine therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Municipal Healthcare Institution "City Clinical Hospital #3", Department of neurology	Chelyabinsk		Russian Federation	454136
2	State Medical Institution "Republican Clinical Hospital of rehabilitation treatment of Ministry of Healthcare of Tatarstan Republic", Republican clinicodiagnostic center of demyelinating diseases of Ministry of Healthcare of Tatarstan Republic	Kazan		Russian Federation	420021
3	State Educational Institution of Higher Professional Education "1st Moscow State Medical University n.a. I.M. Sechenov of Ministry of Healthcare and Social Development of the Russian Federation, Department of new drugs research	Moscow		Russian Federation	119991
4	State Healthcare Institution 'Rostov Regional Clinical Hospital' Center of Neurology	Rostov-on-Don		Russian Federation	344015
5	LLC "International Clinic MEDEM", Department of functional diagnostics	Saint Petersburg		Russian Federation	191025
6	State Educational Institution of Higher Professional Education "St. Petersburg State Medical University n.a. I.V. Pavlov of Roszdrav", Department of neurology with clinic	Saint Petersburg		Russian Federation	197022
7	State Healthcare Institution "Samara Regional Clinical Hospital n.a. M.I. Kalinin", Department of neurosurgery	Samara		Russian Federation	443095
8	State Educational Institution of Higher Professional Education Saratov State Medical University	Saratov		Russian Federation	410012
9	State Educational Institution of Higher Professional Education "Smolensk State Medical Academy of Roszdrav", Department of neurology and neurosurgery based at State Healthcare Institution "Smolensk Regional Clinical Hospital"	Smolensk		Russian Federation
10	St. Petersburg State Healthcare Institution "City multifield hospital #2", Department of neurology #2	St Petersburg		Russian Federation	194354
11	Institution of the Russian Academy of Science "Institute of Human Brain of RAS", Neuroimmunology Laboratory	St Petersburg		Russian Federation	197376
12	North Staffordshire Royal Infirmary	Stoke on Trent	Staffordshire	United Kingdom	ST4 7LN
13	National Hospital for Neurology & Neurosurgery	London		United Kingdom	WC1N 3BG
14	Queen's Medical Centre	Nottingham		United Kingdom	NG7 2UH
15	Peninsula Medical School	Plymouth		United Kingdom	PL6 8BX
16	Royal Hallamshire Hospital	Sheffield		United Kingdom	S10 2 JF

Sponsors and Collaborators

• Apitope Technology (Bristol) Ltd.
• Aptiv Solutions
• ClinStar, LLC

Investigators

• Principal Investigator: Jeremy Chataway, National Hospital for Neurology and Neurosurgery, London

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• sponsor

Publications

None provided.

• Responsible Party: Apitope Technology (Bristol) Ltd.
• ClinicalTrials.gov Identifier: NCT01097668
• Other Study ID Numbers: ATX-MS-1467-002
• First Posted: Apr 2, 2010
• Last Update Posted: Feb 16, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by Apitope Technology (Bristol) Ltd.: Multiple sclerosis; Immunomodulation; Phase 1
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis

Study Results

Participant Flow

Recruitment Details	Screening and study procedures were performed at hospital clinics within the United Kingdom and Russian Federation.
Pre-assignment Detail	Subjects were human lymphocyte antigen (HLA)-DRB1*15 positive with relapsing-remitting multiple sclerosis as defined by the McDonald criteria and as assessed by a neurologist.

Arm/Group Title	Intradermal Injection	Subcutaneous Injection
Arm/Group Description	Upward titration over 4 dose levels (injections of 25, 50, 100 and 400 ug) of ATX MS 1467 followed by injections of 800 ug injected on 5 occasions. All injections were administered at intervals of 14±3 days.	Upward titration over 4 dose levels (injections of 25, 50, 100 and 400 ug) of ATX MS 1467 followed by injections of 800 ug injected on 5 occasions. All injections were administered at intervals of 14±3 days.
Period Title: Overall Study
STARTED	21	22
Week 20	21	22
Week 48	19	20
COMPLETED	19	20
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Intradermal Injection	Subcutaneous Injection	Total
Arm/Group Description	Injections of ATX-MS-1467 given by the intradermal route	Injections of ATX-MS-1467 given by the subcutaneous route	Total of all reporting groups
Overall Participants	21	22	43
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	33.0	31.6	32.3
Sex: Female, Male (Count of Participants)
Female	17 81%	13 59.1%	30 69.8%
Male	4 19%	9 40.9%	13 30.2%
Region of Enrollment (participants) [Number]
Russian Federation	14 66.7%	20 90.9%	34 79.1%
United Kingdom	7 33.3%	2 9.1%	9 20.9%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability
Description	Occurrence of treatment emergent Adverse Events (AE), Serious Adverse Events, and laboratory abnormalities up to week 48 compared to baseline.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

The Safety population will be denoted as the 'ITT population' for the summarisation of safety endpoints.

Arm/Group Title	Intradermal Injection	Subcutaneous Injection
Arm/Group Description	Injections of ATX-MS-1467 administered by the intradermal route	Injections of ATX-MS-1467 administered by the subcutaneous route
Measure Participants	21	22
Number [participants]	21 100%	22 100%

2. Secondary Outcome

Title	The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI).
Description	Number of new or persisting Gadolinium-enhancing lesions at week 16 and 20 when compared to baseline.
Time Frame	16 and 20 weeks

Outcome Measure Data

Analysis Population Description

ITT population at week 16 and 20 n=21 (Intradermal injection) ITT population at week 16 and 20 n=22 (Subcutaneous injection) MRI population at week 16 and 20 n=17 (Intradermal injection) MRI population at week 16 and 20 n=20 (Subcutaneous injection)

Arm/Group Title	Intradermal	Subcutaneous Injection
Arm/Group Description	Injections of ATX-MS-1467 administered by intradermal route	Injections of ATX-MS-1467 administered by subcutaneous route
Measure Participants	21	22
ITT poulation at baseline	5.05	2.09
ITT population at Week 16	0.74	1.85
ITT population at Week 20	1.65	1.47
MRI population at baseline	3.41	2.3
MRI population at Week 16	0.73	1.71
MRI population at Week 20	1.51	1.20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intradermal Injection
	Comments	Comparison of the baseline 'ITT population' MRI data with week 16 data.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	negative binomial model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Intradermal Injection
	Comments	Comparison of the baseline 'MRI population' data with data from week 16.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	negative binomial model
	Comments

Adverse Events

Time Frame	Adverse event data collected over the course of the study = 52 weeks
Adverse Event Reporting Description	Adverse Events were recorded in the Case Report Form and characterised by severity, relationship to IMP,outcome, action taken, onset and resolution date and seriousness. Occurrences of Multiple Sclerosis relapses were recorded as Adverse Events.
Arm/Group Title	Intradermal Injection - Treatment Emergent		Subcutaneous Injection - Treatment Emergent		Intradermal Injection - Non Treatment Emergent		Subcutaneous Injection - Non Treatment Emergent
Arm/Group Description	Injections will be administered by the intradermal route		Injections will be administered by the subcutaneous route		Follow-up period		Follow-up period
All Cause Mortality
	Intradermal Injection - Treatment Emergent		Subcutaneous Injection - Treatment Emergent		Intradermal Injection - Non Treatment Emergent		Subcutaneous Injection - Non Treatment Emergent
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Intradermal Injection - Treatment Emergent		Subcutaneous Injection - Treatment Emergent		Intradermal Injection - Non Treatment Emergent		Subcutaneous Injection - Non Treatment Emergent
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/21 (4.8%)		0/22 (0%)		2/21 (9.5%)		1/22 (4.5%)
Nervous system disorders
Multiple Sclerosis Relapse	1/21 (4.8%)		0/22 (0%)		2/21 (9.5%)		1/22 (4.5%)
Other (Not Including Serious) Adverse Events
	Intradermal Injection - Treatment Emergent		Subcutaneous Injection - Treatment Emergent		Intradermal Injection - Non Treatment Emergent		Subcutaneous Injection - Non Treatment Emergent
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/21 (81%)		16/22 (72.7%)		7/21 (33.3%)		5/22 (22.7%)
Blood and lymphatic system disorders
Anaemia	0/21 (0%)		2/22 (9.1%)		0/21 (0%)		0/22 (0%)
General disorders
Injection Site Reactions	12/21 (57.1%)		7/22 (31.8%)		0/21 (0%)		0/22 (0%)
Immune system disorders
Anti-peptide Antibody response	0/21 (0%)		0/22 (0%)		0/21 (0%)		0/22 (0%)
Infections and infestations
Nasopharyngitis	3/21 (14.3%)		1/22 (4.5%)		1/21 (4.8%)		1/22 (4.5%)
Respiratory Tract Infection	2/21 (9.5%)		0/22 (0%)		1/21 (4.8%)		0/22 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	2/21 (9.5%)		0/22 (0%)		0/21 (0%)		0/22 (0%)
Nervous system disorders
Headache	3/21 (14.3%)		3/22 (13.6%)		1/21 (4.8%)		0/22 (0%)
Multiple sclerosis relapse	2/21 (9.5%)		3/22 (13.6%)		4/21 (19%)		4/22 (18.2%)
Skin and subcutaneous tissue disorders
Rash pruritic	1/21 (4.8%)		0/22 (0%)		0/21 (0%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If the Investigator drafts a publication, he/she agrees to send it to Apitope for review and comment before its submission to the journal. If Apitope considers that the proposed publication contains patentable material or information which should be protected as valuable confidential information, Apitope reserves the right to delay submission to the journal until patent applications have been filed and/or require the deletion of the confidential information from the proposed publication.