Multiple SclerosisPhase 1/2NCT01448252
T Cell Vaccination in Patients With Progressive Multiple Sclerosis
A Phase 1/2 study testing multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides) and T cell vaccination in people with Multiple Sclerosis, run by Hadassah Medical Organization at 1 site in Israel.
Trial summary
This is a double blind phase I-II clinical trial with multiple autologous T cell vaccinations using T cell lines reactive to 9 different myelin peptides of MBP, MOG and PLP, in patients with relapsing progressive Multiple Sclerosis. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides) and T cell vaccination
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteIsrael
- Study dates
- May 2002to Mar 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Clinically definite MS (according to Poser's criteria) of the relapsing-progressive type (RPMS).
- Age: 18-60.
- EDSS: 3.0 to 7.0.
- Disease duration: > 1 year.
- Evidence of disease progression of 1 degree in the EDSS scale, or at least two severe relapses (requiring hospitalization and treatment) during the year prior to inclusion.
- MRI of the brain with at least 5 lesions in the white matter (T2 imaging).
- Failure to benefit from other existing treatments according to the guidelines of the Israeli Ministry of Health.
Who cannot join
- Patients with other systemic active disease.
- Patients who had been treated with immunosuppressive drugs during the 3-6 months depending on the cytotoxicity of the medication used prior to the inclusion.
- Patients who previously received cellular immunotherapy or who are participating in other experimental protocols.
- Pregnancy; Pregnant women or women who do not use efficacious contraception (oral contraception, or intra-uterine device).
- Patients with an additional autoimmune condition unrelated to MS or significant allergy.
- Patients who cannot fully understand the treatment protocol or are unable to sign the informed consent, or in whom the clinician believes that a follow-up period of at least 12 months will not be possible.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Autologous T Cell Vaccination With Line Specific for 9 Myelin Peptides in Patients With Progressive / Relapsing Multiple Sclerosis
This is a double blind phase I-II clinical trial with multiple autologous T cell vaccinations using T cell lines reactive to 9 different myelin peptides of MBP, MOG and PLP, in patients with relapsing progressive Multiple Sclerosis.
Read the detailed description
This trial is a phase I/II double-blind controlled clinical trial designed to evaluate the safety and clinical efficacy of multiple autologous T-cell vaccinations (on days 1, 30, 90 and 180) in progressive MS patients which showed severe progression/deterioration in the functional status (at least, one degree in the EDSS scale) during the last year, or at least one severe relapse. The patients will be from our MS clinic and will be randomized (by computer) into two groups according to: age, disease duration, disease severity and progression rate. One group (2/3 of the patients) will receive the active treatment, i.e. TCV, and the other group (1/3 of the patients) will receive sham treatment (injection of sterile normal saline). The treating nurse, the treating physician, the examining neurologist (the one who will perform the neurological evaluation) and the patient will be blinded for the treatment.
OBJECTIVES AND SIGNIFICANCE OF THE TRIAL
- To develop a new cell therapeutic modality for treating MS patients using attenuated autologous anti-MBP, anti-PLP and anti-MOG autoreactive T-cells as vaccines. The immune response induced by this vaccination will be directed specifically against the T-cells attacking the patient's nerve system (specifically the myelin sheath).
- To study and characterize these autoreactive T-cells in MS patients. The number and function of such cells in the course of the relapse of the disease, as well as during the periods of remissions, will be studied.
- To study the clinical efficacy of T-cell vaccination with attenuated anti-MBP and anti-MOG autologous T-cells on MS. The parameters to be examined will include: change in the disability status (by the EDSS disability scale, as well as by ambulation index and several other functional tests), the change in the relapse rate and in the timed 10-meters walking test, the PASAT test and the 9-hole peg test. MRI parameters will represent additional endpoints and will include: the changes in the total burden of the disease and in the quantity of irreversible damage (cortical atrophy and axonal loss). In addition, the effects of this treatment on the immune responses (i.e. number and proportion of activated lymphocytes, number and proportion of anti-myelin reactive lymphocytes in the peripheral blood and IgG antibody levels in the cerebrospinal fluid) will be evaluated in the treated MS patients.
The significance and importance of the study are outlined as follows:
- It offers a new approach for the treatment of MS.
- This approach has the advantage of being devoid of toxic or general immunosuppressive effects.
- The study will pave the way for further studies that will improve our understanding of the mechanisms of the host immune response in MS and of the involvement of the MBP, PLP and MOG myelin proteins in the initiation of the auto-reactive immune response and of clinical MS.
- Conditions
- Multiple Sclerosis
- Being tested
- multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides), T cell vaccination
- Keywords
- T cell vaccination, Immunotherapy, Tolerance, safety, clinical efficacy
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides)Biological
Also called multiple subcutenous injections of saline at days 1, 30,90,180.
multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides at days 1, 30,90,180
T cell vaccinationBiological
Multiple injections of autologous T cell lines reactive to 9 myelin peptides.
| Study group | Role | What they receive |
|---|---|---|
| TCV | Active comparator | multiple T cell vaccinations against nine myelin peptides at days 1, 30, 90, 180 Receives: Biological: T cell vaccination |
| Placebo | Sham comparator | saline injections subcutaneously at the same 4 time points with active treatment Receives: Biological: multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides) |
What is being measured
The primary outcome is the main question the study is designed to answer.
EDSS changes
Follow up in changes in the EDSS score
Measured: one year
Relapse rate of MS
recording of the relapses of MS during the year of the study and the prior to the study
Measured: one year follow up
PASAT test
recording of the performance in the PASAT test during the one year of the study
Measured: one year
Nine hole PEG test
recording of the performance in the Nine hole PEG test test during the one year of the study
Measured: one year
timed ten meter walking
recording of the performance in the timed ten meter walking test during the one year of the study
Measured: one year
Secondary outcomes (1)
Quantitative MRI evaluation
the burden of T2 lesions load, of the hypo-intense T1 lesions, of the Gadolinium enhancing lesions and of the brain atrophy will be evaluated at the end of the study and compared to the baseline values
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2011 (estimated)
- Study startMay 2002
- Primary completionSep 2008
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dimitrios Karussis, Hadassah Medical Organization
- Investigators
- Dimitrios Karussis, Prof., Principal investigator, Hadassah Medical OrganizatinRivka Abulafia-Lapid, PhD, Study director, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01448252
- Sponsor's protocol ID
- TCV-HMO-CTIL
- Other IDs
- 27-15.15.00
- Status last verified
- Oct 2011
- First submitted
- 5 Oct 2011
- Last updated
- 7 Oct 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Karussis D, Shor H, Yachnin J, Lanxner N, Amiel M, Baruch K, Keren-Zur Y, Haviv O, Filippi M, Petrou P, Hajag S, Vourka-Karussis U, Vaknin-Dembinsky A, Khoury S, Abramsky O, Atlan H, Cohen IR, Abulafia-Lapid R. T cell vaccination benefits relapsing progressive multiple sclerosis patients: a randomized, double-blind clinical trial. PLoS One. 2012;7(12):e50478. doi: 10.1371/journal.pone.0050478. Epub 2012 Dec 14.
PubMed 23272061
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous T Cell Vaccination With Line Specific for 9 Myelin Peptides in Patients With Progressive / Relapsing Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01448252
- Acronym / sponsor ID
- TCV-HMO-CTIL
- Conditions
- Multiple Sclerosis
- Keywords
- T cell vaccination, Immunotherapy, Tolerance, safety, clinical efficacy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- May 2002
- Primary completion
- Sep 2008 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 7 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double blind phase I-II clinical trial with multiple autologous T cell vaccinations using T cell lines reactive to 9 different myelin peptides of MBP, MOG and PLP, in patients with relapsing progressive Multiple Sclerosis.
Detailed description
This trial is a phase I/II double-blind controlled clinical trial designed to evaluate the safety and clinical efficacy of multiple autologous T-cell vaccinations (on days 1, 30, 90 and 180) in progressive MS patients which showed severe progression/deterioration in the functional status (at least, one degree in the EDSS scale) during the last year, or at least one severe relapse. The patients will be from our MS clinic and will be randomized (by computer) into two groups according to: age, disease duration, disease severity and progression rate. One group (2/3 of the patients) will receive the active treatment, i.e. TCV, and the other group (1/3 of the patients) will receive sham treatment (injection of sterile normal saline). The treating nurse, the treating physician, the examining neurologist (the one who will perform the neurological evaluation) and the patient will be blinded for the treatment.
OBJECTIVES AND SIGNIFICANCE OF THE TRIAL
- To develop a new cell therapeutic modality for treating MS patients using attenuated autologous anti-MBP, anti-PLP and anti-MOG autoreactive T-cells as vaccines. The immune response induced by this vaccination will be directed specifically against the T-cells attacking the patient's nerve system (specifically the myelin sheath).
- To study and characterize these autoreactive T-cells in MS patients. The number and function of such cells in the course of the relapse of the disease, as well as during the periods of remissions, will be studied.
- To study the clinical efficacy of T-cell vaccination with attenuated anti-MBP and anti-MOG autologous T-cells on MS. The parameters to be examined will include: change in the disability status (by the EDSS disability scale, as well as by ambulation index and several other functional tests), the change in the relapse rate and in the timed 10-meters walking test, the PASAT test and the 9-hole peg test. MRI parameters will represent additional endpoints and will include: the changes in the total burden of the disease and in the quantity of irreversible damage (cortical atrophy and axonal loss). In addition, the effects of this treatment on the immune responses (i.e. number and proportion of activated lymphocytes, number and proportion of anti-myelin reactive lymphocytes in the peripheral blood and IgG antibody levels in the cerebrospinal fluid) will be evaluated in the treated MS patients.
The significance and importance of the study are outlined as follows:
- It offers a new approach for the treatment of MS.
- This approach has the advantage of being devoid of toxic or general immunosuppressive effects.
- The study will pave the way for further studies that will improve our understanding of the mechanisms of the host immune response in MS and of the involvement of the MBP, PLP and MOG myelin proteins in the initiation of the auto-reactive immune response and of clinical MS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TCV | Active comparator | Biological: T cell vaccinationmultiple T cell vaccinations against nine myelin peptides at days 1, 30, 90, 180 |
| Placebo | Sham comparator | Biological: multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides)saline injections subcutaneously at the same 4 time points with active treatment |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Clinically definite MS (according to Poser's criteria) of the relapsing-progressive type (RPMS).
- Age: 18-60.
- EDSS: 3.0 to 7.0.
- Disease duration: > 1 year.
- Evidence of disease progression of 1 degree in the EDSS scale, or at least two severe relapses (requiring hospitalization and treatment) during the year prior to inclusion.
Key exclusion criteria (6 listed)
- Patients with other systemic active disease.
- Patients who had been treated with immunosuppressive drugs during the 3-6 months depending on the cytotoxicity of the medication used prior to the inclusion.
- Patients who previously received cellular immunotherapy or who are participating in other experimental protocols.
- Pregnancy; Pregnant women or women who do not use efficacious contraception (oral contraception, or intra-uterine device).
- Patients with an additional autoimmune condition unrelated to MS or significant allergy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides)Also: multiple subcutenous injections of saline at days 1, 30,90,180.multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides at days 1, 30,90,180 | Biological | Placebo |
| T cell vaccinationMultiple injections of autologous T cell lines reactive to 9 myelin peptides. | Biological | TCV |
Primary outcome
EDSS changes
Time frame: one year
Follow up in changes in the EDSS score
Relapse rate of MS
Time frame: one year follow up
recording of the relapses of MS during the year of the study and the prior to the study
PASAT test
Time frame: one year
recording of the performance in the PASAT test during the one year of the study
Nine hole PEG test
Time frame: one year
recording of the performance in the Nine hole PEG test test during the one year of the study
timed ten meter walking
Time frame: one year
recording of the performance in the timed ten meter walking test during the one year of the study
1 secondary outcome
Quantitative MRI evaluation
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2011.
- Derived from this study: PubMed 23272061Karussis D, Shor H, Yachnin J, Lanxner N, Amiel M, Baruch K, Keren-Zur Y, Haviv O, Filippi M, Petrou P, Hajag S, Vourka-Karussis U, Vaknin-Dembinsky A, Khoury S, Abramsky O, Atlan H, Cohen IR, Abulafia-Lapid R. T cell vaccination benefits relapsing progressive multiple sclerosis patients: a randomized, double-blind clinical trial. PLoS One. 2012;7(12):e50478. doi: 10.1371/journal.pone.0050478. Epub 2012 Dec 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dimitrios Karussis, Prof. principal investigator
Hadassah Medical Organizatin
Rivka Abulafia-Lapid, PhD study director
Hadassah Medical Organization
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides) and T cell vaccination in people with Multiple Sclerosis, run by Hadassah Medical Organization at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
EDSS changes (time frame: one year). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01448252, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2011.