Efficacy and Safety of IGIV-C in Corticosteroid Dependent Patients With Generalized Myasthenia Gravis
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| ClinicalTrials.gov Identifier: NCT02473965 |
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Recruitment Status :
Completed
First Posted : June 17, 2015
Results First Posted : February 26, 2020
Last Update Posted : March 30, 2020
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Sponsor:
Grifols Therapeutics LLC
Information provided by (Responsible Party):
Grifols Therapeutics LLC
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Brief Summary:
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) as a corticosteroid (CS)-sparing agent in subjects with CS-dependent Myasthenia Gravis (MG).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Myasthenia Gravis | Drug: IGIV-C Drug: Placebo | Phase 2 |
This study consists of 2 phases: IGIV-C Run-in Phase and Corticosteroid Tapering/IGIV-C Maintenance Phase.
In the Run-in Phase, subjects will receive a total of 3 doses of IGIV-C (1 loading dose of 2 g/kg and 2 maintenance doses of 1 g/kg) while maintaining a stable dose of corticosteroids.
In the CS Tapering/IGIV-C Maintenance Phase, subjects will continue 1 g/kg IGIV-C and begin a prescribed CS tapering regimen where the CS dose is decreased every 3 weeks.
Approximately 60 subjects are planned to be enrolled in the study across multiple centers in North America and Europe. The total duration of study participation for each subject is up to 45 weeks.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of lGIV-C as a Corticosteroid Sparing Agent in Corticosteroid Dependent Patients With Generalized Myasthenia Gravis |
| Study Start Date : | June 2015 |
| Actual Primary Completion Date : | February 2019 |
| Actual Study Completion Date : | February 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Myasthenia gravis
| Arm | Intervention/treatment |
|---|---|
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Experimental: IGIV-C
An IGIV-C loading dose of 2 g/kg and maintenance dose of 1 g/kg will be administered in CS dependent subjects with MG.
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Drug: IGIV-C
Run-Phase: 1 loading dose of 2 g/kg IGIV-C and 2 maintenance doses of 1 g/kg IGIV-C Corticosteroid Tapering/IGIV-C Maintenance Phase: 1 g/kg IGIV-C every 3 weeks for up to 36 weeks |
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Placebo Comparator: Placebo
0.9% sodium chloride injection, USP or equivalent
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Drug: Placebo |
Primary Outcome Measures :
- Percent of Subjects Achieving a 50% or Greater Reduction in CS Dose (Prednisone or Equivalent) From Baseline to Week 39 [ Time Frame: Baseline/Week 0 (Visit 1) and Week 39 (Visit 14). ]The average daily CS dose was derived for each subject at each scheduled visit based on the prescribed dose and the time interval taking into account any prescribed dose changes between routinely scheduled visits. Subjects who discontinued the study early with adverse outcomes related to MG were considered as not achieving a 50% or greater reduction. The missing dose reduction at Week 39 was imputed using the worst observation carried forward (WOCF) method. For subjects who did not have CS dose prescribed at Week 39 due to other reasons, the last observation carried forward (LOCF) method was used to impute the prescribed CS dose at Week 39. Baseline was defined as the last non-missing measurement taken prior to first dose of study medication. The percent of subjects achieving ≥50% reduction in CS dose from baseline to Week 39 is presented for each treatment group overall and for the baseline daily prednisone equivalent dose level stratification categories.
Secondary Outcome Measures :
- Mean Percent Change in Daily CS Dose (Prednisone or Equivalent) From Baseline to Week 39 [ Time Frame: Baseline/Week 0 (Visit 1) and Week 39 (Visit 14). ]The average daily CS dose was derived for each subject at each scheduled visit based on the prescribed dose and the time interval taking into account any prescribed dose changes between routinely scheduled visits. For subjects who discontinued the study early with adverse outcomes related to MG, the missing dose reduction at Week 39 was imputed using the WOCF method. For subjects who had missing CS dose reduction at Week 39 due to other reasons, the missing CS dose was imputed using the LOCF method. Baseline was defined as the last non-missing measurement taken prior to first dose of study medication. The least squares (LS) mean percent change from baseline in daily CS dose to Week 39 is presented for each treatment group.
- Median Time to First Episode of MG Worsening [ Time Frame: From Baseline/Week 0 (Visit 1) to Week 39 (Visit 14). ]The time to the first episode of MG worsening was defined as the time between baseline and the first instance of QMG total score increase by ≥4 points relative to Baseline/Week 0. The QMG total score is the sum of all 13 items and ranges from 0 to 39. Higher values represent greater severity of illness. If one or more items were missing at a given assessment, the total score was set to missing. The median time to MG worsening was calculated based on Kaplan-Meier methodology. Baseline was defined as the last non-missing measurement taken prior to the first dose of study medication.
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| Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Anti-acetylcholine receptor antibody positive
- Confirmed diagnosis of generalized MG historically meeting the clinical criteria for diagnosis of MG defined by the Myasthenia Gravis Foundation of America (MGFA) classification of Class II, III, IV, or V historically
- At Screening, subjects may have symptoms controlled by CS or were MGFA Class II-IVa inclusive (Class IVb and Class V excluded). Subjects who only have a history of ocular MG may not enroll.
- On systemic CS for a minimum period of at least 3 months and on a stable CS dose of >=15 mg/day and <=60 mg/day (prednisone equivalent) for the month prior to Screening.
- Had a tapering CS dose that the study investigator considered to be appropriate.
- At least 1 previous completed attempt to taper CS in order to minimize CS dose (lowest feasible dose based on observed MG signs and symptoms)
Exclusion Criteria:
- Any dose change in concomitant immunosuppressant therapy, other than CS, in the prior 6 months
- Any change in CS dose or acetylcholinesterase inhibitor (e.g., pyridostigmine) dose in the 1 month prior to Screening
- A 3-point change in Quantitative Myasthenia Gravis score, increased or decreased, between the Screening/Week -3 (Visit 0) and Baseline (Week 0 [Visit 1])
- Any episode of myasthenic crisis (MC) in the 1 month prior to Screening, or (at any time in the past) MC or hospitalization for MG exacerbation associated with a previous CS taper attempt
- Evidence of malignancy within the past 5 years (non-melanoma skin cancer, carcinoma in situ of cervix is allowed) or thymoma potentially requiring surgical intervention during the course of the trial (intent to perform thymectomy)
- Thymectomy within the preceding 6 months prior to Screening
- Rituximab, belimumab, eculizumab or any monoclonal antibody used for immunomodulation within the past 12 months prior to Screening
- Have received immune globulin treatment given by IV, subcutaneous, or intramuscular route within the last 3 months prior to Screening
- Received plasma exchange performed within the last 3 months prior to Screening
- History of anaphylactic reactions or severe reactions to any blood-derived product
- History of recent (within the last year) myocardial infarction or stroke
- Uncontrolled congestive heart failure; embolism; or historically documented (within the last year) electrocardiogram changes indicative of myocardial ischemia or atrial fibrillation
- Current known hyperviscosity or hypercoagulable state
- Currently receiving anti-coagulation therapy. Oral anti-platelet agents are allowed (e.g., aspirin, clopidogrel, ticlopidine)
- Females of child-bearing potential who are pregnant, have a positive serum pregnancy test, breastfeeding, or are unwilling to practice a highly effective method of contraception throughout the study.
- Renal impairment
- Aspartate aminotransferase or alanine aminotransferase levels exceeding more than 2.5 times the upper limit of normal for the expected normal range for the testing laboratory.
- Hemoglobin (Hb) levels <9 g/dL
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02473965
Locations
Show 39 study locations
Sponsors and Collaborators
Grifols Therapeutics LLC
Study Documents (Full-Text)
Documents provided by Grifols Therapeutics LLC:
Documents provided by Grifols Therapeutics LLC:
Statistical Analysis Plan [PDF] April 12, 2019
Study Protocol [PDF] December 23, 2016
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Grifols Therapeutics LLC |
| ClinicalTrials.gov Identifier: | NCT02473965 |
| Other Study ID Numbers: |
GTI1306 |
| First Posted: | June 17, 2015 Key Record Dates |
| Results First Posted: | February 26, 2020 |
| Last Update Posted: | March 30, 2020 |
| Last Verified: | March 2020 |
Additional relevant MeSH terms:
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Myasthenia Gravis Muscle Weakness Muscular Diseases Musculoskeletal Diseases Neuromuscular Manifestations Neurologic Manifestations Nervous System Diseases Pathologic Processes Paraneoplastic Syndromes, Nervous System Nervous System Neoplasms |
Neoplasms by Site Neoplasms Paraneoplastic Syndromes Autoimmune Diseases of the Nervous System Neurodegenerative Diseases Neuromuscular Junction Diseases Neuromuscular Diseases Autoimmune Diseases Immune System Diseases |