Myositis, Inclusion BodyPhase 2NCT00079768
Alemtuzumab to Treat Sporadic Inclusion Body Myositis
A Phase 2 study testing Alemtuzumab (Campath) in people with Myositis, Inclusion Body, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will examine the safety and effectiveness of alemtuzumab (Campath® (Registered Trademark)) for improving muscle strength in patients with sporadic inclusion body myositis (s-IBM). Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Myositis, Inclusion Body
- What is being tested?
- Alemtuzumab (Campath)
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2004to Mar 2007
- Phase
- Phase 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 25 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with confirmed diagnosis of s-IBM willing to undergo therapy with Alemtuzumab.
- Willingness and legal ability to give and sign informed study consent.
- Willingness to travel to the Clinical Center for planned studies and treatment as required by protocol.
- Men and women of reproductive potential must agree to use an acceptable method of birth control during and for six months after completion of treatment.
- Availability of tissue for testing. This will include muscle and peripheral blood lymphocytes isolated through routine lymphocytapheresis or phlebotomy.
Who cannot join
- Immunosuppressive drug therapy at the time of or 6 months prior to enrollment. Specifically, candidates may not be taking Prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, anti-lymphocyte agents, cyclophosphamide methotrexate, or other agents whose concomitant use may enhance the toxicity of Alemtuzumab.
- Any medical or personal difficulties that precludes serial follow-up visits.
- Any active malignancy.
- Significant coagulopathy or requirement for anticoagulation therapy that would contraindicate protocol.
- Platelet count less than 100,000/mm(3).
- Hemoglobin less than 9.0 mg/dl.
Show all 14Show fewer
- Any known immunodeficiency syndrome included HIV infection.
- Any history of cardiac insufficiency, major vascular disease, or unstable coronary artery disease.
- Any history of systemic or pulmonary edema.
- Any history of previous treatment with monoclonal antibodies or sensitivity to the study drug (Alemtuzumab), pre-medication regimen, or prophylactic agents.
- History of chronic hypotension (SBP less than 100 mmHg).
- Any medical condition that would likely increase the risk of side effects of the study drug or confound the interpretation of the data including active infections.
- Pregnancy and active nursing (breast feeding).
- History of uncontrolled thyroid disease or a history of autoimmune thyroiditis.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Effects of a T Cell-Depleting Monoclonal Antibody, Alemtuzumab, in Patients With Inclusion Body Myositis: A Pilot Clinicopathological Study
This study will examine the safety and effectiveness of alemtuzumab (Campath® (Registered Trademark)) for improving muscle strength in patients with sporadic inclusion body myositis (s-IBM). The most common inflammatory muscle disease in people over the age of 50, s-IBM progresses steadily, leading to severe weakness and wasting of the muscles in the arms and legs. The cause of s-IBM is not known, but it may be an autoimmune disease, in which the body's immune cells (white blood cells) attack and destroy parts of muscle. Alemtuzumab is a laboratory-made antibody currently approved to treat certain leukemias. It has also been used to treat patients with autoimmune conditions such as rheumatoid arthritis, vasculitis, multiple sclerosis, and tissue rejection associated with transplantation. Alemtuzumab destroys white blood cells that have a protein called CD52 on their surface and that might be among the cells attacking muscle.
Patients with s-IBM are eligible for this study. Candidates are screened with physical and neurological examinations, blood tests, and an electrocardiogram. Participants undergo the following tests and procedures:
- Campath administration: Patients are admitted to the NIH Clinical Center for 1 to 1-1/2 weeks for intravenous infusions of Campath, given every other day for a total of 4 infusions.
- Follow-up visits after infusions: Patients are monitored for up to 1 year with periodic blood tests, physical and neurological examinations, medical history, muscle strength measurements, and a review of symptoms, including the ability to perform daily living activities.
- Lymphapheresis: Patients undergo this procedure for collecting large numbers of white blood cells twice - once at the beginning of the study and again after 6 months. Blood is removed through a needle in an arm vein and flows through a machine that separates it into its components by centrifugation (spinning). The white cells and plasma are removed and the red cells and platelets are returned to the patients through the same needle or through another needle in the other arm.
- Muscle biopsy: Muscle biopsies are done in the operating room under local anesthetic. A small incision is made in the thigh or upper arm and a small piece of muscle is removed. Biopsies are done at the beginning of the study and again after 6 months.
Read the detailed description
Sporadic Inclusion-Body Myositis (s-IBM) is the most common muscle disease in patients above the age of 50 years. It is an inflammatory myopathy mediated by sensitized, cytotoxic CD8+ T cells that clonally expand in situ and invade MHC-I-expressing muscle fibers. The antigen recognized by the T cells is unknown. The disease is progressive, resists the currently available immunotherapies and leads to wheelchair confinement. Applying therapeutic strategies with agents that deplete T cells clones and investigating the antigenic specificity of the endomysial T cells is expected to enhance our understanding of the cause of s-IBM and lead to clinical improvement. The present study is designed to: a) test in a pilot study the safety, T cell depletion of the endomysial T cells and clinical efficacy of the monoclonal antibody Alemtuzumab in 20 patients with s-IBM followed for 12 months by serial quantitative assessment of muscle strength; b) explore the spectrum of the antigens recognized by the T cells extracted from the muscle biopsy specimens by searching for immune dominant peptides using positional scanning synthetic combinational peptide libraries, before and after therapy; and c) determine the reciprocal relationship between clinical response and endomysial inflammatory mediators before and after treatment. It is anticipated that the study may lead to identification of putative antigens that trigger the disease, clarify the significance of the inflammation and amyloid deposits in muscle fiber injury and provide a novel therapy for s-IBM patients.
- Conditions
- Myositis, Inclusion Body
- Being tested
- Alemtuzumab (Campath)
- Keywords
- Inflammation, Myositis, Humanized Monoclonal Antibody, Cytotoxic T Cells, Endomysial T Cells, Alemtuzumab, Monoclonal Antibodies, IBM, Anti-CD 52, Inclusion Body Myositis
- Medical subject headings
- Myositis, Inclusion Body, Inflammation, Myositis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alemtuzumab (Campath)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the muscle strength at 6 months by 15%.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2004 (estimated)
- Study startMar 2004
- Primary completionMar 2007
- Study completionMar 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Myositis, Inclusion BodyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Enrolment
- 20 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00079768
- Sponsor's protocol ID
- 040133
- Other IDs
- 04-N-0133
- Status last verified
- Jan 2009
- First submitted
- 12 Mar 2004
- Last updated
- 17 Jun 2010
- Results posted
- No
Publications
Dalakas MC. Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med. 1991 Nov 21;325(21):1487-98. doi: 10.1056/NEJM199111213252107. No abstract available.
PubMed 1658649Dalakas MC, Sonies B, Dambrosia J, Sekul E, Cupler E, Sivakumar K. Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study. Neurology. 1997 Mar;48(3):712-6. doi: 10.1212/wnl.48.3.712.
PubMed 9065553Dalakas MC, Koffman B, Fujii M, Spector S, Sivakumar K, Cupler E. A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM. Neurology. 2001 Feb 13;56(3):323-7. doi: 10.1212/wnl.56.3.323.
PubMed 11171896Dalakas MC, Rakocevic G, Schmidt J, Salajegheh M, McElroy B, Harris-Love MO, Shrader JA, Levy EW, Dambrosia J, Kampen RL, Bruno DA, Kirk AD. Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain. 2009 Jun;132(Pt 6):1536-44. doi: 10.1093/brain/awp104. Epub 2009 May 19.
PubMed 19454532
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of a T Cell-Depleting Monoclonal Antibody, Alemtuzumab, in Patients With Inclusion Body Myositis: A Pilot Clinicopathological Study
- ClinicalTrials.gov ID
- NCT00079768
- Acronym / sponsor ID
- 040133
- Conditions
- Myositis, Inclusion Body
- Keywords
- Inflammation, Myositis, Humanized Monoclonal Antibody, Cytotoxic T Cells, Endomysial T Cells, Alemtuzumab, Monoclonal Antibodies, IBM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Mar 2004
- Primary completion
- Mar 2007 (actual)
- Study completion
- Mar 2007 (actual)
- First posted
- 12 Mar 2004 (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 study will examine the safety and effectiveness of alemtuzumab (Campath® (Registered Trademark)) for improving muscle strength in patients with sporadic inclusion body myositis (s-IBM). The most common inflammatory muscle disease in people over the age of 50, s-IBM progresses steadily, leading to severe weakness and wasting of the muscles in the arms and legs. The cause of s-IBM is not known, but it may be an autoimmune disease, in which the body's immune cells (white blood cells) attack and destroy parts of muscle. Alemtuzumab is a laboratory-made antibody currently approved to treat certain leukemias. It has also been used to treat patients with autoimmune conditions such as rheumatoid arthritis, vasculitis, multiple sclerosis, and tissue rejection associated with transplantation. Alemtuzumab destroys white blood cells that have a protein called CD52 on their surface and that might be among the cells attacking muscle.
Patients with s-IBM are eligible for this study. Candidates are screened with physical and neurological examinations, blood tests, and an electrocardiogram. Participants undergo the following tests and procedures:
- Campath administration: Patients are admitted to the NIH Clinical Center for 1 to 1-1/2 weeks for intravenous infusions of Campath, given every other day for a total of 4 infusions.
- Follow-up visits after infusions: Patients are monitored for up to 1 year with periodic blood tests, physical and neurological examinations, medical history, muscle strength measurements, and a review of symptoms, including the ability to perform daily living activities.
- Lymphapheresis: Patients undergo this procedure for collecting large numbers of white blood cells twice - once at the beginning of the study and again after 6 months. Blood is removed through a needle in an arm vein and flows through a machine that separates it into its components by centrifugation (spinning). The white cells and plasma are removed and the red cells and platelets are returned to the patients through the same needle or through another needle in the other arm.
- Muscle biopsy: Muscle biopsies are done in the operating room under local anesthetic. A small incision is made in the thigh or upper arm and a small piece of muscle is removed. Biopsies are done at the beginning of the study and again after 6 months.
Detailed description
Sporadic Inclusion-Body Myositis (s-IBM) is the most common muscle disease in patients above the age of 50 years. It is an inflammatory myopathy mediated by sensitized, cytotoxic CD8+ T cells that clonally expand in situ and invade MHC-I-expressing muscle fibers. The antigen recognized by the T cells is unknown. The disease is progressive, resists the currently available immunotherapies and leads to wheelchair confinement. Applying therapeutic strategies with agents that deplete T cells clones and investigating the antigenic specificity of the endomysial T cells is expected to enhance our understanding of the cause of s-IBM and lead to clinical improvement. The present study is designed to: a) test in a pilot study the safety, T cell depletion of the endomysial T cells and clinical efficacy of the monoclonal antibody Alemtuzumab in 20 patients with s-IBM followed for 12 months by serial quantitative assessment of muscle strength; b) explore the spectrum of the antigens recognized by the T cells extracted from the muscle biopsy specimens by searching for immune dominant peptides using positional scanning synthetic combinational peptide libraries, before and after therapy; and c) determine the reciprocal relationship between clinical response and endomysial inflammatory mediators before and after treatment. It is anticipated that the study may lead to identification of putative antigens that trigger the disease, clarify the significance of the inflammation and amyloid deposits in muscle fiber injury and provide a novel therapy for s-IBM patients.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with confirmed diagnosis of s-IBM willing to undergo therapy with Alemtuzumab.
- Willingness and legal ability to give and sign informed study consent.
- Willingness to travel to the Clinical Center for planned studies and treatment as required by protocol.
- Men and women of reproductive potential must agree to use an acceptable method of birth control during and for six months after completion of treatment.
- Availability of tissue for testing. This will include muscle and peripheral blood lymphocytes isolated through routine lymphocytapheresis or phlebotomy.
Key exclusion criteria (14 listed)
- Immunosuppressive drug therapy at the time of or 6 months prior to enrollment. Specifically, candidates may not be taking Prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, anti-lymphocyte agents, cyclophosphamide methotrexate, or other agents whose concomitant use may enhance the toxicity of Alemtuzumab.
- Any medical or personal difficulties that precludes serial follow-up visits.
- Any active malignancy.
- Significant coagulopathy or requirement for anticoagulation therapy that would contraindicate protocol.
- Platelet count less than 100,000/mm(3).
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 |
|---|---|---|
| Alemtuzumab (Campath) | Drug | – |
Primary outcome
Change in the muscle strength at 6 months by 15%.
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 17 Jun 2010.
- Background: PubMed 1658649Dalakas MC. Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med. 1991 Nov 21;325(21):1487-98. doi: 10.1056/NEJM199111213252107. No abstract available.
- Background: PubMed 9065553Dalakas MC, Sonies B, Dambrosia J, Sekul E, Cupler E, Sivakumar K. Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study. Neurology. 1997 Mar;48(3):712-6. doi: 10.1212/wnl.48.3.712.
- Background: PubMed 11171896Dalakas MC, Koffman B, Fujii M, Spector S, Sivakumar K, Cupler E. A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM. Neurology. 2001 Feb 13;56(3):323-7. doi: 10.1212/wnl.56.3.323.
- Derived from this study: PubMed 19454532Dalakas MC, Rakocevic G, Schmidt J, Salajegheh M, McElroy B, Harris-Love MO, Shrader JA, Levy EW, Dambrosia J, Kampen RL, Bruno DA, Kirk AD. Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain. 2009 Jun;132(Pt 6):1536-44. doi: 10.1093/brain/awp104. Epub 2009 May 19.
Related trials for Myositis, Inclusion Body
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingObservational study
Imaging Assessment of Swallowing and Speech Muscles in Inclusion Body Myositis
IBM, Inclusion Body Myositis
RecruitingObservational study
Adult and Juvenile Myositis
Dermatomyositis, Polymyositis
Not yet recruitingPhase 4
Emerging Indications for Hyperbaric Oxygen Treatment
Post-COVID-19 Condition, Ulcerative Colitis
Active, not recruitingObservational study
The Aim of the Study is to Characterize Patients Exhibiting Muscular Atrophy and Weakness Who Require a Muscle Biopsy for Diagnosis (IBM vs Atypical MND), Through an Innovative Technique Which Enables the Evaluation of the Neuromuscular Junction Involvement in Each Condition
Inclusion Body Myositis (IBM), Motor Neuron Disease, Amyotrophic Lateral Sclerosis
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alemtuzumab (Campath) in people with Myositis, Inclusion Body, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
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 5 inclusion and 14 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 17 Jun 2010. 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 United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Change in the muscle strength at 6 months by 15%.. 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 NCT00079768, which also lists 4 linked publications.
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 17 Jun 2010.