Alemtuzumab in Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIPD)
Primary Purpose
Chronic Inflammatory Demyelinating Neuropathy
Status
Withdrawn
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Alemtuzumab infusion
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Inflammatory Demyelinating Neuropathy focused on measuring CIDP- chronic inflammatory demyelinating neuropathy, demyelinating neuropathy, alemtuzumab
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent form (ICF).
- Men or women aged ≥18 years as of the date the ICF is signed.
- 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.
- 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.
- Duration of CIDP > 6 months prior to the date the ICF is signed.
- Treating neurologist and participant in agreement that alemtuzumab is an appropriate treatment and documents this is in clinical notes.
Exclusion Criteria:
- Previous treatment with alemtuzumab.
- 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).
- Intolerance of pulsed corticosteroids.
- 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.
- Presence of neurogenic sphincter disturbance.
- Multifocal motor neuropathy (fulfilling EFNS/PNS (European Federation of Neuroscience/Peripheral Nerve Society) criteria).
- Atypical CIDP with pure sensory or persistent uni-focal impairment or significant CNS involvement.
- Active infection, e.g., deep-tissue infection that the Investigator considers sufficiently serious to preclude study participation.
- 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).
- Known infection with or seropositivity for human immunodeficiency virus (HIV).
- Previous or present infection with hepatitis C virus.
- Previous or present infection with hepatitis B (positive hepatitis B serology).
- Prior history of invasive fungal infections.
- Latent tuberculosis, unless effective anti-tuberculosis therapy has been completed, or active tuberculosis
- 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).
- 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.
- Absolute neutrophil count below the LLN at screening. If abnormal cell counts return to with in normal limits, eligibility may be reassessed.
- 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.
- 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.
- 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).
- Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (i.e., above LLN).
- History of malignancy (exception for basal cell skin carcinoma).
- Major psychiatric disorder not adequately controlled by treatment.
- History of substance abuse within the last 2 years.
- Epileptic seizures not adequately controlled by treatment.
- Of child bearing potential with a positive serum pregnancy test,pregnant,or lactating.
- 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]).
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
- 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.
- Immunocompromise of any type which would in the view of the investigator make the risk of alemtuzumab treatment unacceptable.
- Previous stem cell transplantation.
Sites / Locations
- The Johns Hopkins Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Alemtuzumab
Arm Description
Open label study of alemtuzumab
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change from baseline in disability measured with Overall Neuropathy Limitations Scale (ONLS) at 36 months.
ONLS is a validated measure of neurological disfunction.
Full Information
NCT ID
NCT01757574
First Posted
December 6, 2012
Last Updated
May 17, 2017
Sponsor
Johns Hopkins University
Collaborators
Genzyme, a Sanofi Company
1. Study Identification
Unique Protocol Identification Number
NCT01757574
Brief Title
Alemtuzumab in Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIPD)
Official Title
An Open-Label Trial of Alemtuzumab in Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIPD)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Withdrawn
Why Stopped
At the request of the global principal investigator, no subjects were enrolled in this study at any site.
Study Start Date
November 2012 (Actual)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
Genzyme, a Sanofi Company
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
This is an open-label multi-center trial of alemtuzumab in the treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). The study will have 4 phases.
Approximately 16 eligible participants will receive at least one cycle of alemtuzumab (5 days of drug infusion). Additional cycles of alemtuzumab (3 days of drug infusion) may be provided at the discretion of the participants' treating physician such as if clinical worsening occurs.
Phase 1: Screening Participants meeting the inclusion and exclusion criteria and having signed the informed consent document will enter the screening phase and undergo baseline evaluations.
Phase 2: Drug Infusion Participants will receive alemtuzumab by infusion using a standardized protocol. Participants will be maintained on their prior CIDP therapy during the drug infusions and then followed at regular intervals.
Phase 3. Alteration of CIDP therapy CIDP therapy may be altered at the discretion of the treating physician - either taper, discontinuation, or increase of current or additional medications. For those participants on chronic corticosteroid therapy, following pulse IV methylprednisolone and alemtuzumab cycle, corticosteroids will be tapered as rapidly and as far as possible according to according to the investigator's discretion. While the aim will be to discontinue corticosteroids, it is recognized that some participants will have a suppressed pituitary-adrenal axis and complete discontinuation may not be possible.
Phase 4: Extended Follow-up Each participant will be followed per protocol for a minimum of 36 months. All participants will undergo safety assessments and monitoring for at least 36 months after the last cycle of alemtuzumab. Additional cycles of alemtuzumab may be provided at the discretion of the participants' treating physician with at least a 12 month interval between cycles.
NUMBER OF PARTICIPANTS: Approximately 16 participants will join this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Inflammatory Demyelinating Neuropathy
Keywords
CIDP- chronic inflammatory demyelinating neuropathy, demyelinating neuropathy, alemtuzumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Alemtuzumab
Arm Type
Experimental
Arm Description
Open label study of alemtuzumab
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab infusion
Primary Outcome Measure Information:
Title
Change from baseline in disability at 36 months measured by GBS/CIDP Rasch-built Overall Disability Scale (GBS/CIDP-RODS).
Description
The RODS CIDP scale is a validated measure of disability in CIDP/GBS.
Time Frame
Every six months up to 36 months
Secondary Outcome Measure Information:
Title
Change from baseline in disability measured with Overall Neuropathy Limitations Scale (ONLS) at 36 months.
Description
ONLS is a validated measure of neurological disfunction.
Time Frame
Every six months up to 36 months
Other Pre-specified Outcome Measures:
Title
Questionnaire survey
Description
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.
Time Frame
Monthly up to 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent form (ICF).
Men or women aged ≥18 years as of the date the ICF is signed.
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.
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.
Duration of CIDP > 6 months prior to the date the ICF is signed.
Treating neurologist and participant in agreement that alemtuzumab is an appropriate treatment and documents this is in clinical notes.
Exclusion Criteria:
Previous treatment with alemtuzumab.
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).
Intolerance of pulsed corticosteroids.
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.
Presence of neurogenic sphincter disturbance.
Multifocal motor neuropathy (fulfilling EFNS/PNS (European Federation of Neuroscience/Peripheral Nerve Society) criteria).
Atypical CIDP with pure sensory or persistent uni-focal impairment or significant CNS involvement.
Active infection, e.g., deep-tissue infection that the Investigator considers sufficiently serious to preclude study participation.
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).
Known infection with or seropositivity for human immunodeficiency virus (HIV).
Previous or present infection with hepatitis C virus.
Previous or present infection with hepatitis B (positive hepatitis B serology).
Prior history of invasive fungal infections.
Latent tuberculosis, unless effective anti-tuberculosis therapy has been completed, or active tuberculosis
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).
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.
Absolute neutrophil count below the LLN at screening. If abnormal cell counts return to with in normal limits, eligibility may be reassessed.
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.
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.
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).
Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (i.e., above LLN).
History of malignancy (exception for basal cell skin carcinoma).
Major psychiatric disorder not adequately controlled by treatment.
History of substance abuse within the last 2 years.
Epileptic seizures not adequately controlled by treatment.
Of child bearing potential with a positive serum pregnancy test,pregnant,or lactating.
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]).
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
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.
Immunocompromise of any type which would in the view of the investigator make the risk of alemtuzumab treatment unacceptable.
Previous stem cell transplantation.
Facility Information:
Facility Name
The Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
12. IPD Sharing Statement
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Alemtuzumab in Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIPD)
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