Anti-3-hydroxy-3-methylglutaryl-CoA Reductase (HMGCR) Immune-Mediated Necrotizing Myopathy
Conditions
Brief summary
This is a randomized, placebo-controlled, double blinded phase 2 exploratory clinical trial of intravenously administered pooled human immunoglobulin (IVIG) in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune mediated necrotizing myopathy (IMNM). Planned enrollment is 12 individuals with active anti-HMGCR IMNM meeting inclusion and exclusion criteria. Assuming 20% drop-out, the investigators anticipate 10 participants will complete all study assessments. Enrolled participants will be randomized 1:1 to either IVIG 2g/kg or placebo (0.9% sodium chloride at equivalent volume) at weeks 0, 4, and 8. The primary efficacy and co-primary safety and tolerability endpoints will be assessed at week 12. After the randomized phase of the trial, all participants will be offered to continue on to an open-label extension phase in which participants will receive IVIG at weeks 12, 16, and 20. Participants will then return at week 24 for a final non-infusion visit to reassess safety, tolerability, and efficacy outcome.
Interventions
BIOLOGICALIntravenously administered pooled human immunoglobulin (IVIG)
IVIG 2g/kg every 4 weeks for 12 weeks (3 doses)
Sponsors
University of Alabama at Birmingham
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Octapharma USA, Inc.
CSI Pharmacy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Using an online randomization tool (e.g. REDCap), 12 total participants will be randomized 1:1 in blocks of 4 to receive either intravenously administered pooled human immunoglobulin (IVIG) 2g/kg every 4 weeks or placebo (0.9% sodium chloride solution at equivalent volume to corresponding IVIG weight-based dose). The home infusion research pharmacy (CSI Pharmacy) will assign treatment status using the randomization tool and will prepare IVIG or placebo for home infusion nursing staff in a blinded fashion.
Intervention model description
A randomized, placebo-controlled, double blinded phase 2 exploratory clinical trial of intravenously administered pooled human immunoglobulin (IVIG) in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune mediated necrotizing myopathy (IMNM). Planned enrollment is 12 individuals with active anti-HMGCR IMNM meeting inclusion and exclusion criteria. Enrolled participants will be randomized 1:1 to receive either IVIG 2g/kg or placebo (0.9% sodium chloride at equivalent volume) at weeks 0, 4, and 8. The 2g/kg q4 weeks regimen of IVIG was chosen based on the investigators' clinical experience and prior studies. The primary endpoints will be assessed at week 12. After the randomized phase of the trial, all participants will be offered an open-label extension to receive IVIG at weeks 12, 16, and 20.
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 16 years * Anti-HMGCR antibody positive * MMT-8 score \< 142 (range 0-160) * Serum CK \> 5x upper limit of normal * Anti-HMGCR IMNM disease duration \< 36 months at screening * No moderate or severe respiratory or swallowing dysfunction due to anti-HMGCR IMNM at screening * No history of dermatomyositis rash * Must reside in a state with a participating research site
Exclusion criteria
* Oral glucocorticoid (GC) daily dose \> 15mg at screening * Change in oral GC dose \< 2 weeks prior to screening * Prior IVIG treatment for anti-HMGCR IMNM -\>1 oral conventional synthetic DMARD (e.g. methotrexate, mycophenolate mofetil, azathioprine) use at screening * Change in concomitant DMARD dose \< 4 weeks prior to screening * Rituximab \< 6 months prior to screening * Plasma exchange, cyclophosphamide, or biologic immunosuppressive medication \< 3 months prior to screening * Use of statin medication at screening * History of anaphylactic reaction to IVIG * History of angina pectoris, myocardial infarction, transient ischemic attack, or stroke \< 12 months prior to screening * Females of child-bearing potential who are pregnant, breastfeeding, or are unwilling to practice a highly effective method of contraception during the study * Wells Criteria for DVT score of 2 or more at screening * Wells Criteria for PE score of 4 or more at screening * Weight \>120kg * History of cancer (excluding non-melanomatous skin cancer) \< 5 years prior to screening * History of pulmonary embolism or deep venous thromboembolism \< 3 years prior to screening * History of hyperviscosity or hypercoagulable state * Currently receiving anti-coagulation therapy (vitamin K antagonists, non-vitamin K oral anticoagulants \[e.g. dabigatran, rivaroxaban, apixaban\], parenteral anticoagulants \[e.g. fondaparinux\]. Note that oral anti-platelet agents are allowed (e.g. aspirin, clopidogrel, ticlopidine). * Glomerular filtration rate (GFR) \<60mL/min at the time of screening * Any medical condition which, in the investigator's judgment, makes participation in the clinical trial unadvisable or which would interfere with evaluation of the study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in serum creatine kinase (CK) | Week 0 to 12 | Primary Efficacy Outcome |
Countries
United States
Contacts
CONTACTJames Andrews, MD
CONTACTHannah E Howell, MS
PRINCIPAL_INVESTIGATORJames Andrews, MD
University of Alabama at Birmingham
Outcome results
None listed