ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12608000226303

Ethics application status

Approved

Date submitted

29/02/2008

Date registered

1/05/2008

Date last updated

7/04/2024

Date data sharing statement initially provided

7/04/2024

Date results provided

7/04/2024

Type of registration

Retrospectively registered

Titles & IDs

Public title

A double-blind, placebo controlled, randomised trial to prove the therapeutic concept and to determine the pharmacokinetic profile of ATL1102 (VLA-4 antisense oligonucleotide) by subcutaneous injections in patients with relapsing remitting multiple sclerosis.

Scientific title

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Multiple Sclerosis

Condition category

Condition code

Neurological

Multiple sclerosis

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Patients receive 200 mg ATL1102 (VLA-4 antisense oligonucleotide) by subcutaneous injection three times in the first week, then twice weekly for the next seven weeks. The patients are monitored for a further eight weeks following completion of dosing.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

1.3 ml placebo comprising sodium chloride and colorant by subcutaneous injection three times in the first week, then twice weekly for the next seven weeks. The patients are monitored for a further eight weeks following completion of dosing.

Control group

Placebo

Outcomes

Primary outcome [1]

Cumulative number of new active lesions on Magnetic Resonance Imaging (MRI), corrected for the number of enhancing lesions at baseline.

Timepoint [1]

At 4, 8 and 12 weeks after intervention commencement.

Secondary outcome [1]

Cumulative volume of gadolinium-enhancing lesions on MRI, corrected for the volume of enhancing lesions at baseline.

Timepoint [1]

At 4, 8 and 12 weeks after intervention commencement.

Eligibility

Key inclusion criteria

Males and females aged 18 to 55 years
Diagnosis of Relapsing Remitting Multiple Sclerosis (RRMS)
At least 9 T2 lesions or at least 4 if one is gadolinium-enhancing
Last relapse in the previous 12 months
No relapse in the previous four weeks
Score of EDSS 0 to 6.0
Reliable contraception (e.g. surgical sterilisation, oral contraceptives)
Written informed consent to participate in the study by signature on the Patients Consent Form

Minimum age

18 Years

Maximum age

55 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Administration of any investigational drug within the previous 2 months before enrolment (4 months if the previous drug was a new chemical entity).
Progressive disease.
Concomitant clinically relevant other findings on MRI that may interfere with outcome assessment.
Previous treatment with VLA-4 antibodies, anti-CD4 antibodies, or other monoclonal antibodies.
Total lymphoid irradiation at any time.
Treatment with immune-modulating drugs in the previous two months or treatment with immune-suppressive drugs in the previous six months.
HIV positive patients.
Detectable levels of JC Virus in the blood measured by quantitative PCR.
Patients with renal impairment with serum creatinine greater than or equal to 2,0 mg/dl.
History of clinically relevant gastrointestinal, hepatic, renal, endocrine, haematological, metabolic, neurologic (other than multiple sclerosis (MS)) and psychiatric disease.
Patients with infections (lymphocytes greater than 3000/microL).
History of any bleeding.
History of coagulation abnormalities.
Concomitant medication acetyl salicylic acid (greater than 300 mg/day) and phenprocoumon.
Clinically relevant abnormalities in physical findings at screening examination if interfering with the study objective.
Pregnant or breast-feeding women.
History of drug or alcohol abuse.
Epileptics.
Suicidal subjects.
History of drug allergy and/or known drug hypersensitivity.
Inability to communicate or cooperate with the Investigator due to language problem, poor mental development or impaired cerebral function.
Any medical condition which, in the judgement of the Investigator, might interfere with the objectives of the study.
Repeated participation in this study.
Contraindication for application of study drug.
Corticoid-treatment in the previous six weeks and during the study period, exceptions are corticoid-treatment before the study period (not in the previous six weeks) and of relapses during the study period: Relapses are characterised by the occurrence of neurological dysfunction symptoms, appearing after a 30-day period of stability or improvement and lasting for more than 24 hours (no infection, no fever).
A 5-day methylprednisolone treatment 1000 mg intravenous (i.v) is allowed in this case followed by a reducing procedure.
Corticoid-treatment if applied locally (e.g. inhaled products) is allowed.
Additionally MRI exclusion criteria: Metal residing in the body (e.g. implants), Cardiac pacemaker, valves, cochlear implants, CNS vascular clips.
Contrast medium allergy Gadolinium Diethylenetriamine Penta-Acetic Acid (Gd-DTPA).
No MRI exclusion criteria but caution is advised in case of: Cardiovascular disease including coronary heart disease, Immune deficiency, Haematologic disorder.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 2

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

19/02/2005

Actual

19/02/2005

Date of last participant enrolment

Anticipated

Actual

17/04/2008

Date of last data collection

Anticipated

Actual

17/04/2008

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

Slovakia

State/province [1]

Country [2]

Poland

State/province [2]

Country [3]

Czech Republic

State/province [3]

Country [4]

Romania

State/province [4]

Country [5]

Bulgaria

State/province [5]

Country [6]

Germany

State/province [6]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Antisense Therapeutics Limited

Address [1]

10 Wallace Avenue, Level 1
Toorak

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Antisense Therapeutics Limited

Address

10 Wallace Avenue, Level 1
Toorak
Vic 3142

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Ethics Committee of the Faculty of Medicine, University of Duisburg-Essen, University Clinic Essen

Ethics committee address [1]

Robert-Koch-Str. 9-11 45147 Essen

Ethics committee country [1]

Germany

Date submitted for ethics approval [1]

Approval date [1]

05/08/2004

Ethics approval number [1]

Idnr: 04-2508

Ethics committee name [2]

Ethics Committee of the State Chamber of Physicians of the Federal State of Hessen

Ethics committee address [2]

Im Vogelsang 3 60488 Frankfurt am Main

Ethics committee country [2]

Germany

Date submitted for ethics approval [2]

Approval date [2]

12/10/2004

Ethics approval number [2]

E 258/2004MC

Ethics committee name [3]

Ethics Committee of the Chamber of Physicians of the Federal State of Lower Saxony, Corporation under Public Law

Ethics committee address [3]

Berliner Allee 20 30175 Hannover

Ethics committee country [3]

Germany

Date submitted for ethics approval [3]

Approval date [3]

05/10/2004

Ethics approval number [3]

Grae 212/2004

Ethics committee name [4]

Ethics Committee of the Chamber of Physicians of the Federal State of Mecklenburg-West Pomerania at the University of Rostock, Institute of Forensic Medicine

Ethics committee address [4]

Postfach 100888 18055 Rostock

Ethics committee country [4]

Germany

Date submitted for ethics approval [4]

Approval date [4]

20/10/2004

Ethics approval number [4]

II SV 68/2004

Ethics committee name [5]

Ethics Committee of the State Chamber of Physicians of Thuringia, Corporation under Public Law

Ethics committee address [5]

Im Semmicht 33 07751 Jena

Ethics committee country [5]

Germany

Date submitted for ethics approval [5]

Approval date [5]

21/10/2004

Ethics approval number [5]

kl/1117/04112

Ethics committee name [6]

Ethics Committee of the Chamber of Physicians of Berlin, Corporation under Public Law

Ethics committee address [6]

Friedrichstrasse 16 10969 Berlin

Ethics committee country [6]

Germany

Date submitted for ethics approval [6]

Approval date [6]

19/01/2005

Ethics approval number [6]

Eth-012/05

Ethics committee name [7]

Ethics Committee of the Medical University of Hannover

Ethics committee address [7]

Carl-Neuberg-Str. 1 30625 Hannover

Ethics committee country [7]

Germany

Date submitted for ethics approval [7]

Approval date [7]

21/03/2005

Ethics approval number [7]

Nr. 3884

Ethics committee name [8]

Ethics Committee of the State Chamber of Physicians of Rhineland-Palatinate, Corporation under Public Law

Ethics committee address [8]

Postfach 2926 55019 Mainz

Ethics committee country [8]

Germany

Date submitted for ethics approval [8]

Approval date [8]

19/09/2006

Ethics approval number [8]

837.253.06 (5351)

Ethics committee name [9]

Ethics Committee of the Chamber of Physicians of Hamburg, Corporation under Public Law

Ethics committee address [9]

Postfach 760109 22051 Hamburg

Ethics committee country [9]

Germany

Date submitted for ethics approval [9]

Approval date [9]

22/08/2006

Ethics approval number [9]

M-206/06

Ethics committee name [10]

Ethics Committee of the Faculty of Medicine, University of Witten/Herdecke

Ethics committee address [10]

Alfred-Herrhausen-Str.50 D58448 Witten

Ethics committee country [10]

Germany

Date submitted for ethics approval [10]

Approval date [10]

24/04/2006

Ethics approval number [10]

Antragsnr. 33/2006

Ethics committee name [11]

MHAT "Tzaritza Ioanna" Ltd Local Ethics Committee

Ethics committee address [11]

Byalo more Str. Sofia 1504, 8

Ethics committee country [11]

Bulgaria

Date submitted for ethics approval [11]

Approval date [11]

31/10/2006

Ethics approval number [11]

231/25.10.2006

Ethics committee name [12]

Local Ethics Committee at SHATNP "Sv. Naum

Ethics committee address [12]

4 km Tsarigradsko shose Blvd.1113 Sofia

Ethics committee country [12]

Bulgaria

Date submitted for ethics approval [12]

Approval date [12]

18/10/2006

Ethics approval number [12]

10/18.10.2006

Ethics committee name [13]

Local Ethics Committee at SHATCVD

Ethics committee address [13]

Sofia, 65 Konyovitsa Str

Ethics committee country [13]

Bulgaria

Date submitted for ethics approval [13]

Approval date [13]

18/10/2006

Ethics approval number [13]

10/18.10.2006

Ethics committee name [14]

MHAT "St. Marina" Ltd. Varna Local Ethics Committee

Ethics committee address [14]

1 Hristo Smirnenski Str. 9010 Varna

Ethics committee country [14]

Bulgaria

Date submitted for ethics approval [14]

Approval date [14]

10/10/2006

Ethics approval number [14]

17/10.10.2006

Ethics committee name [15]

Ethics Committee FN Olomouc

Ethics committee address [15]

I.P. Pavlova 6 77520 Olomouc

Ethics committee country [15]

Czech Republic

Date submitted for ethics approval [15]

Approval date [15]

11/12/2006

Ethics approval number [15]

174/06 MEK 44

Ethics committee name [16]

Ethics Committee of Slezska Nemocnice Opava

Ethics committee address [16]

Olomoucka 86 Opava, 74601

Ethics committee country [16]

Czech Republic

Date submitted for ethics approval [16]

Approval date [16]

03/05/2007

Ethics approval number [16]

Ethics committee name [17]

Ethics Commitee of FNKV

Ethics committee address [17]

Scrobarova 50 100 34 Praha 10

Ethics committee country [17]

Czech Republic

Date submitted for ethics approval [17]

Approval date [17]

05/01/2007

Ethics approval number [17]

Ethics committee name [18]

Ethics Committee of District Hospital Pardubice

Ethics committee address [18]

Kyjevska 44 53203 Pardubice

Ethics committee country [18]

Czech Republic

Date submitted for ethics approval [18]

Approval date [18]

17/01/2007

Ethics approval number [18]

Ethics committee name [19]

Ethics Committee at FNsP Bratislava Ruzinov Facility

Ethics committee address [19]

Ruzinovska 6 82606 Bratislava

Ethics committee country [19]

Slovakia

Date submitted for ethics approval [19]

Approval date [19]

14/11/2006

Ethics approval number [19]

2006-004736-79

Ethics committee name [20]

Ethics Committee at FNsP BratislavaSt.cyril and Method Hospital pracovisko Petrzalka

Ethics committee address [20]

Antolska 11 85107 Bratislava

Ethics committee country [20]

Slovakia

Date submitted for ethics approval [20]

Approval date [20]

14/11/2006

Ethics approval number [20]

Ethics committee name [21]

Ethics committee at University Hospital Nitra

Ethics committee address [21]

Spitalska 6 PP41C 95001 Nitra

Ethics committee country [21]

Slovakia

Date submitted for ethics approval [21]

Approval date [21]

20/12/2006

Ethics approval number [21]

Ethics committee name [22]

Bioethical Committee of Medical University of Lodz

Ethics committee address [22]

Al. Kosciuszki 4 90-419 Lodz

Ethics committee country [22]

Poland

Date submitted for ethics approval [22]

Approval date [22]

16/01/2007

Ethics approval number [22]

RNN/4/07KE

Ethics committee name [23]

Ministry of Health National Ethics Committee

Ethics committee address [23]

Av. Sanatescu 48 sector 1 Bucharest

Ethics committee country [23]

Romania

Date submitted for ethics approval [23]

Approval date [23]

14/11/2006

Ethics approval number [23]

Nr. 4302

Summary

Brief summary

Background: Antisense oligonucleotides (ASOs) are an innovative new class of drugs that inhibit the expression of proteins by sequence-specific binding to the protein’s mRNA. ATL1102 is a 2nd generation antisense inhibitor of CD49d, a subunit of Very Late Antigen 4 (VLA-4) which plays a key role in cell adhesion to vessel walls. VLA-4 blockade, as shown by monoclonal antibodies such as natalizumab, prevents activated lymphocytes from migrating into the CNS and significantly reduces disease activity in MS.

Objective: To evaluate VLA-4 Antisense (ATL1102) in the treatment of RR-MS

Methods: Randomized, double-blind, placebo-controlled multicenter Phase-IIa trial. 77 patients with RR-MS were treated for 8 weeks with either 200mg of ATL1102 or placebo subcutaneously twice weekly and evaluated for 16 weeks. MRI scans were performed at screening, and then monthly over 16 weeks. Primary efficacy variable: cumulative number of new active lesions (CNNAL; new gadolinium-enhancing T1 lesions (T1-Gd), new or enlarging T2 lesions) on MRIs taken at weeks 4, 8 and 12. Secondary efficacy variable: cumulative volume of T1-Gd lesions (CVT1L) on MRIs taken at weeks 4, 8 and 12. 

Results: ITT population: 74 patients with a valid baseline MRI and at least one post-baseline MRI scan after first injection of study medication (n=39 placebo, n=35 ATL1102). ATL1102 showed a significant reduction, 54.4%, in CNNAL (6.2 placebo, 3.0 ATL1102; p=0.01). A reduction of 66.7% (p=0.002) was observed in the cumulative number (weeks 4,8,12) of new T1-Gd lesions with ATL1102. A reduction in CVT1L was also observed under ATL1102 but did not reach significance (589.4 mm3 placebo, 358.0 mm3 ATL1102; p=0.1068). Adverse events that were more frequent under ATL1102 included mild to moderate injection site reactions and a tendency for decreased platelet counts which were reversible after treatment interruption.

Conclusions: This proof-of-concept study of a drug designed to inhibit VLA-4 mRNA showed a significant reduction of the cumulative number of new active lesions in RR-MS patients following 8 weeks of treatment. These promising results warrant further investigation.

Trial website

Trial related presentations / publications

VLA-4 Antisense – An Oligonucleotide targeting VLA-4 mRNA (ATL1102) significantly reduces new active lesions in patients with RR-MS. Volker Limmroth, Frederik Barkhof, Nuket Desem, for the ATL1102 Study Group 
Presented at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal Canada on 20 September 2008 and at the American Academy of Neurology (AAN) 61st Annual Meeting in Seattle, Washington USA on 29 April 2009 by the Principal Investigator of the trial, Volker Limmroth MD PhD.
 
ATL/TV1102, an oligonucleotide targeting VLA-4 mRNA, significantly reduces new active lesions in patients with relapsing remitting multiple sclerosis.
Volker Limmroth, Frederik Barkhof, Nuket Desem
Presented at the New York Academy of Sciences Annual Meeting of the Oligonucleotide Therapeutics Society, Boston Massachusetts, USA on 18 October 2008 by Dr Christopher Wraight, Research Director, Antisense Therapeutics Ltd. 
 
ATL1102, an Antisense Drug Targeting VLA-4, Significantly Reduces the Development of Active Lesions in Relapsing-Remitting Multiple Sclerosis.
Volker Limmroth, Frederik Barkhof, Nuket Desem
Presented at the Keystone Symposia scientific conference entitled ‘Therapeutic Modulation of RNA Using Oligonucleotides’, in Alberta Canada on 13 February 2009 by Nuket Desem, Development Director, Antisense Therapeutics Ltd.

Public notes

Contacts

Principal investigator

Name

Prof Volker Limmroth

Address

Cologne-Merheim Hospital
Clinic for Neurology
Ostmerheimer Str. 200
51109 Cologne

Country

Germany

Phone

+49 221 89070

Fax

info@kliniken-koeln.de

Contact person for public queries

Name

Susan Turner

Address

Level 30, 35 Collins Street
MELBOURNE VIC 3000

Country

Australia

Phone

+61 3 9827 8999

Fax

+61 3 9827 1166

susan.turner@percherontx.com

Contact person for scientific queries

Name

Andrew McKenzie

Address

Level 30, 35 Collins Street
Melbourne Vic 3000

Country

Australia

Phone

+61 3 9827 8999

Fax

+61 3 9827 1166

andrew.mckenzie@percherontx.com

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS.	2014	https://dx.doi.org/10.1212/WNL.0000000000000926
Embase	Antisense oligonucleotides: The next frontier for treatment of neurological disorders.	2018	https://dx.doi.org/10.1038/nrneurol.2017.148
Embase	Clinical advances of RNA therapeutics for treatment of neurological and neuromuscular diseases.	2022	https://dx.doi.org/10.1080/15476286.2022.2066334
Embase	Targeting integrins in drug-resistant acute myeloid leukaemia.	2024	https://dx.doi.org/10.1111/bph.16149

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

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