Apitope study
The study drug (ATX-MS-1467) is a new investigational drug being tested as a potential treatment for relapsing forms of multiple sclerosis (RMS). The term ‘investigational drug’ means it has not been approved for general use by government health authorities such as the United Kingdom
Medicines and Healthcare Products Regulatory Agency (MHRA), but it may be tested in research studies such as this one.
The purpose of this study is to test the safety of this drug in humans and to evaluate the effects of ATX-MS-1467 on the underlying causes of Multiple Sclerosis.
ATX-MS-1467 has undergone tests in laboratory models and no significant problems were seen in any of these tests. The drug has also been tested in a previous clinical trial in six people with secondary progressive MS.
During this previous study, the people reported minimal side effects. Recruitment
Start date: April 2010
End date: Recruitment will continue until enrolment is fully completed Phase
Phase I
Who can enter the trial
You may be eligible to take part in this trial if:
• You are male or female and aged 18 years to 55 years
• You have RMS and have been diagnosed in the last 10 years • You have had one relapse episode in the past 12 months or two
relapses in the past 24 months
• You have tested positive for the genetic variant HLA DRB1*15 • You have had no treatment medication for your MS in the last three
months and are clinically stable or in an improving neurological state during the 28 days before the screening visit
• You have an EDDS of less than or equal to 5.5
• You are able to adhere to the study visit schedule and other protocol requirements
• You are capable of giving written informed consent. Contraception
If you are female and of childbearing age/potential, you must have a negative pregnancy test at the start of the trial and use two forms of effective contraception simultaneously during the treatment and should continue such precautions for three months after receiving the last dose of
study medication. Women must not be breastfeeding or trying to conceive when taking part in this study
If you are male you must be willing to use contraception to avoid
pregnancies throughout the entire duration of the study and for the three months after receiving the last dose of study medication.
Consent must be obtained prior to any screening procedures. Exclusion Criteria
You cannot take part in this trial if you have been treated with any of the following medications or procedures prior to taking part in the study or are currently taking the following medication:
• Interferon beta, plasma exchange, intravenous gamma globulin within the three months prior to day one of the study
• Glatiramer acetate at any time in the past
• Steroids (administered via the oral or parenteral routes) or
adrenocorticotropic hormone (ACTH) within the three months prior to day one of the study
• Cytotoxic agents: examples include cladribine, mitoxantrone, cyclophosphamide, azathioprine, methotrexate), fingolimod, laquinimod, teriflunomide, total lymphoid irradiation, stem cell or bone marrow transplantation, or monoclonal antibody therapy
(including natalizumab, daclizumab and alemtuzumab) at any time in the past
• T-cell vaccine or peptide-tolerising agent to treat MS at any time in the past
• Any Investigational drug or experimental procedure within the six months prior to day one of the study, including cytokine or anti-cytokine therapy
• You have inadequate liver function, defined by a total bilirubin, AST, ALT or alkaline phosphatase >2.5 times the upper limit of the normal values at the screening or pre-dose visits
• You have any major medical illness such as cardiac, endocrinologic, hepatic, immunologic (other than MS), metabolic, genito-urinary, pulmonary, dermatologic, gastrointestinal, or other major disease that would mean you could not receive the study drug
• You have a known history of any active or chronic infectious or any condition which compromises immune function.
• You have any renal condition that would prevent you receiving Gadolinium
• You have a clinically significant abnormal thyroid function test at the screening or pre–dose visit.
• You are unable to undergo MRI testing or have a Gadolinium allergy • You have secondary progressive MS.
• You have detectable levels of antibodies specific for any of the peptides within the study medication at the screening visit. • You are unable to give informed consent or there are any other
reasons, in the opinion of the trial investigators, which exclude you from taking part in the study.
• You have undergone major surgery in the four weeks before the screening visit
• You have another autoimmune condition.
You must tell your study doctor about all medicines you are using or intend to use during the study – some of these may mean that you cannot take part. Some medicines are not allowed during the study, your study doctor will tell you about these.
Trial design
The study will involve approximately 10 people with RMS in the UK and it is planned that a further 30 patients will be recruited in Russia.
If participants are eligible and agree to take part in this study, they will be participating for a total duration of about one year, including up to 25 visits to the clinic.
Each study visit is likely to take approximately three hours and each MRI scan will take an additional one hour.
The study consists of the following Phases:
A screening period - up to eight weeks before receiving the study drug, Participants will have two physical examinations and a brain scan which will be assessed by a brain scanning technique called “magnetic
resonance imaging” (MRI). They will also undergo other tests including blood tests. One of the blood tests performed during the screening period will confirm if they have a specific version of a gene in their body which makes them suitable for the study. It is essential for participants to have these tests before being included in the study.
A dosing period - from the first day of receiving the study drug to week 16: Participants will receive one or two injections of the study drug every two weeks (nine doses in total) in or under the skin of either the upper or lower stomach or thigh. The study drug is a clear colourless liquid. The first 20 people included in the study, will be given the injections between the layers of their skin (intradermal injection). The next 20 people included in the study, will be given injections under the skin (subcutaneous injection). The study doctor will tell participants which sort of injections they will receive.
Please note:
The amount of study drug you receive will increase over the first five sets of injections and then remain constant for the remaining four sets of injections. Participants will receive the study drug once every two weeks for a period of 16 weeks (nine doses in total). The study staff will prepare and administer the injections and answer any questions.
On the days that participants receive the study drug, they will need to stay at the clinic for at least two hours after the injection. Also on these days they will have a physical examination and other assessments including blood tests. They will also need to have a monthly MRI scan in the weeks before they are given the study drug injections.
There will be a follow up period - from 20 weeks to 48 weeks after
receiving the first injection of study drug. During this time participants will visit the clinic four times for various assessments to check that they are well and a further four times for MRI scans.
If the study doctor feels it is needed, people may be asked to come in for more visits.
What is expected of participants
Once consent is given by participants to be involved in the study, they will attend screening visit to determine if they are eligible for the study.
If eligible for the study they will be asked to return for a visit prior to the start of the study drug being administered.
Participants will then be asked to attend the clinic every 2 weeks to receive the study drug and various assessments up to 16 weeks. The study doctor and staff will supervise the time in the clinic. One or two injections of the study drug will be given to each participant every two weeks until a total of nine doses of the study drug have been given to each participant with relapsing multiple sclerosis over the 16 week period.
Participants will be asked to attend 4 more follow-up visits up to 48 weeks to check that they are well. If employed, study participants may need to take time off in order to come to the clinic for study visits.
It is recommended that when people come for their visits, they travel by taxi or have a friend or family member bring them by car. They should avoid coming alone or using other forms of public transport for their visits if possible. The study sponsor will reimburse for travel expenses.
Participants will be expected to follow the study doctor’s instructions: If people feel unwell, they must tell the study doctor straight away. An emergency contact card with the study identification and study doctor’s 24 hour contact details on it will need to be carried at all times.
The study diaries that you are given must be completed accurately and fully.
Participants must let the study doctor know about any prescription drugs that they are taking or start to take during the study or any over the
counter drugs that they are taking or start to take during the study. They may or may not be able to continue taking these drugs during the study as they may interfere with the study drug.
People taking part in the study must not have participated in a drug
research study during the previous 3 months from the last day of receiving the study drug in a previous study.
The study participants must agree to use the study medication only as instructed by the study doctor and their staff.
Side effects
As with any research study, there may be risks associated with the administration of the study drug and risks of participating which are currently unknown and have not been foreseen. It is possible, although extremely unlikely that your condition could be made worse by exposure to the study drug.
In a previous study, six people with secondary progressive multiple sclerosis were given the same study drug. Side effects reported in one person included muscle spasms in both legs and decreased stability in both legs, which were considered possibly related to the study drug and improved in a short time period.
UK locations of the trial
Up to 10 sites in the UK, including:
National Hospital for Neurology & Neurosurgery (NHNN), London North Staffordshire Royal Infirmary, Stoke-on-Trent
Peninsula Medical School, Derriford Hospital, Plymouth John Radcliffe Hospital, Oxford
Royal Hallamshire Hospital, Sheffield
If you are interested in finding out more, please contact: Marie Braisher at the NHNN Tel: 0207 6922363 (m.braisher@ion.ucl.ac.uk)
Contact details
If you are interested in this trial you should discuss this information with your neurologist, doctor or health care professional for further advice. For more information about the Apitope study please visit:
http://www.apitope.com/pipeline/clinical_trials_MS.html Chief Investigator
Dr Jeremy Chataway, National Hospital for Neurology & Neurosurgery, London
Supported by:
Apitope Technology (Bristol) Ltd National MS Society
Fast Forward National MS Trust
