Chronic Inflammatory Demyelinating Neuropathy Clinical Trial
Official title:
An Open-Label Trial of Alemtuzumab in Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIPD)
| Verified date | May 2017 |
| Source | Johns Hopkins University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The objectives of this study are to determine the safety, tolerability and preliminary
efficacy of alemtuzumab for infusion for the treatment of CIDP. Eligible subjects will be
treated with alemtuzumab at the beginning of the study and then followed for three years.
During the three year period, subjects will under go monthly safety evaluations consisting
of blood and urine testing, symptom surveys and examination. Detailed neurological testing
including nerve conduction testing, Rasch-built Overall Disability Scale (CIDP/RODS) and
Overall Neuropathy Limitations Scale (ONLS) assessments will be performed every six months
for three years.
The study will also investigate and compare the responsiveness of the outcome measures being
used.
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | August 2016 |
| Est. primary completion date | August 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. Signed informed consent form (ICF). 2. Men or women aged =18 years as of the date the ICF is signed. 3. Diagnosis of CIDP made by a consultant neurologist with a special interest in peripheral neuropathy. CIDP may be diagnosed in the presence of diabetes or IgG(immunoglobulin- G), IgA and IgM paraproteins without anti- MAG (myelin associated glycoprotein) antibodies. Documentation of the initial diagnosis including definite neurophysiological criteria proposed by INCAT (lnflammatory Neuropathy Cause and Treatment) or EFNS/PNS (European Federation of Neuroscience/Peripheral Nerve Society) must be available for review. 4. Ongoing treatment(s) for CIDP to include IVIg (Intravenous immune globulin) or corticosteroids only. Other treatments for CIDP including plasma exchange, azathioprine, methotrexate and mycophenolate must be washed out for 3 months. Cyclophosphamide, rituximab and other monoclonal antibodies must be washed out for 12 months. 5. Duration of CIDP > 6 months prior to the date the ICF is signed. 6. Treating neurologist and participant in agreement that alemtuzumab is an appropriate treatment and documents this is in clinical notes. Exclusion Criteria: 1. Previous treatment with alemtuzumab. 2. Participation in a controlled trial of an investigational medicinal product within the past 12 weeks. The duration of required washout will be established based on the known biological and pharmacokinetic properties of the investigational drug (prior treatment with herbal medications or nutritional supplements is permitted). 3. Intolerance of pulsed corticosteroids. 4. Alternative cause of peripheral neuropathy such as drug or toxin, hereditary neuropathy or concomitant diseases such as HIV infection, Lyme disease, chronic active hepatitis, systemic lupus erythematosus, IgM paraprotein with anti-MAG (myelin associated glycoprotein) antibodies, vasculitis, thyroid dysfunction, hematological and non- hematological malignancies. 5. Presence of neurogenic sphincter disturbance. 6. Multifocal motor neuropathy (fulfilling EFNS/PNS (European Federation of Neuroscience/Peripheral Nerve Society) criteria). 7. Atypical CIDP with pure sensory or persistent uni-focal impairment or significant CNS involvement. 8. Active infection, e.g., deep-tissue infection that the Investigator considers sufficiently serious to preclude study participation. 9. In the Investigator's opinion, is at high risk for infection (e.g., in-dwelling catheter, dysphagia, decubitus ulcer, history of prior aspiration pneumonia or recurrent urinary tract infection). 10. Known infection with or seropositivity for human immunodeficiency virus (HIV). 11. Previous or present infection with hepatitis C virus. 12. Previous or present infection with hepatitis B (positive hepatitis B serology). 13. Prior history of invasive fungal infections. 14. Latent tuberculosis, unless effective anti-tuberculosis therapy has been completed, or active tuberculosis 15. Cervical high risk human papillomavirus (HPV) positivity or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS). The participant may be eligible after the condition has resolved (e.g., follow-up HPV (human papilloma virus) test is negative or cervical abnormality has been effectively treated). 16. CD4+ (cluster of differentiation - 4), CD8+ , or CD19+ cell count (i.e., absolute CD3+CD4+, CD3+CD8+, or CD19+/mm3) cell count <lower limit of normal (LLN) at Screening. If abnormal cell counts return to within normal limits, eligibility may be reassessed. 17. Absolute neutrophil count below the LLN at screening. If abnormal cell counts return to with in normal limits, eligibility may be reassessed. 18. Confirmed platelet count <LLN of the evaluating laboratory at Screening or documented at <100,000/µL within the past year on a sample without platelet clumping. 19. Known bleeding disorder (e.g.,dysfibrinogenemia, factor IX deficiency, hemophilia, vonWillebrand's disease, disseminated intravascular coagulation (DIC), fibrinogen deficiency, clotting factor deficiency) or chronic use of anticoagulant treatment. 20. Significant other active autoimmune disease, besides CIDP (e.g., immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, severe psoriasis, thyroiditis). 21. Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (i.e., above LLN). 22. History of malignancy (exception for basal cell skin carcinoma). 23. Major psychiatric disorder not adequately controlled by treatment. 24. History of substance abuse within the last 2 years. 25. Epileptic seizures not adequately controlled by treatment. 26. Of child bearing potential with a positive serum pregnancy test,pregnant,or lactating. 27. Unwilling to agree to use a reliable and acceptable contraceptive method throughout the study period (all participants of reproductive potential). Reliable and effective contraceptive method(s) include: intrauterine device (IUD), hormonal-based contraception, surgical sterilization, abstinence, or double- barrier contraception (condom and occlusive cap [diaphragm or cervical cap with spermicide]). 28. Any hepatorenal function value grade 2 or higher at screening (see Table below, drawn from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0 (CTCAE), released 12 December 2003), with the exception of hyperbilirubinemia due to Gilbert's syndrome: Hepatic Bilirubin >1.5x ULN (upper limit of normal) SGOT/AST >2.5x ULN SGPT/ALT >2.5x ULN Alkaline phosphatase >2.5x ULN Renal Creatinine >1.5x ULN 29. Other conditions that,in the Investigator's opinion,compromise the participant's ability to understand the participant information, to give informed consent, to comply with the trial protocol, or to complete the study. 30. Immunocompromise of any type which would in the view of the investigator make the risk of alemtuzumab treatment unacceptable. 31. Previous stem cell transplantation. |
| Country | Name | City | State |
|---|---|---|---|
| United States | The Johns Hopkins Hospital | Baltimore | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| Johns Hopkins University | Genzyme, a Sanofi Company |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Questionnaire survey | At monthly intervals, participants will undergo routine blood monitoring and complete a questionnaire survey. All physicians, study staff and participants will be given ITP and Goodpasture's disease education. | Monthly up to 36 months | |
| Primary | Change from baseline in disability at 36 months measured by GBS/CIDP Rasch-built Overall Disability Scale (GBS/CIDP-RODS). | The RODS CIDP scale is a validated measure of disability in CIDP/GBS. | Every six months up to 36 months | |
| Secondary | Change from baseline in disability measured with Overall Neuropathy Limitations Scale (ONLS) at 36 months. | ONLS is a validated measure of neurological disfunction. | Every six months up to 36 months |