Monotherapy IVIG Gamunex-C for HMG-CoA Reductase Auto-Antibody Positive Necrotizing Myopathy Treatment (The MIGHT Trial)

• Status: Recruiting
• Trial end date: 2022-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase 2, pilot, randomized, placebo-controlled trial of Gamunex-C IVIG as mono-therapy for HMGCoA reductase auto-antibody positive (HMGCR) necrotizing myopathy. The trial will test the feasibility and initial efficacy of Gamunex-C IVIG mono-therapy in HMGCR necrotizing myopathy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Washington
• Collaborator: Grifols Biologicals, LLC
• Treatments: Immunoglobulins, Intravenous

Criteria

Inclusion Criteria:

A subject must meet all of the following inclusion criteria at screening to be eligible for participation in this study:

• Anti-HMGCR positive. Patients will be screened by commercially-available ELISA.

• Age ≥ 18 years

• Demonstrable proximal muscle weakness: score of <135 on the Proximal Manual Muscle Strength Testing 8-Muscle Group Assessment (MMT-8) (range 0-160).

• Serum creatinine kinase (CK) more than 5 times the upper limit of normal

• Muscle biopsy will not be required for eligibility in order to minimize the time to enrollment and initiation of treatment. Muscle biopsy will be obtained whenever possible as part of the standard of care.

• Subjects must be willing and able to provide written informed consent.

Exclusion Criteria:

A subject meeting any of the following exclusion criteria at screening is NOT eligible for participation in this study:

• Disease duration greater than 36 months.

• Currently taking glucocorticoids.

• Participants will need to be tapered off all glucocorticoids by their treating physician over an interval deemed appropriate, and be free of steroid use for at least 14 days prior to the time of study screening in order to be eligible.

• Exposure to immunoglobulin treatment (IV, IM, or SubQ) in the prior 3 months

• Exposure to plasma exchange (PEX) in the prior 3 months

• Exposure to other immunosuppressive medications (e.g. methotrexate, leflunomide, azathioprine, mycophenolate mofetil) in the prior 6 months

• Exposure to rituximab or any monoclonal antibody in the prior 12 months

• Exposure to a statin in the prior 3 months

• History of dermatomyositis rash (either biopsy-proven, or history of photosensitive rash).

• Presence of respiratory or swallowing dysfunction due to HMGCR myopathy

• Inadequate venous access

• History of anaphylactic reactions or severe reactions to any blood-derived product

• History of intolerance to any component of the IP

• History of thrombotic complication to polyclonal IVIG therapy

• History of pulmonary embolism or deep venous thromboembolism

• History of hyperviscosity or hypercoagulable state

• History of myocardial infarction or stroke in the last 12 months

• 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, ticodipine).

• Females of child-bearing potential who are pregnant, have a positive serum pregnancy test (human chorionic gonadotropin [HCG]-based assay), breastfeeding, or are unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence*) throughout the study.

• True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.)

• Renal impairment (i.e., serum creatinine exceeds more than 1.5 times the upper limit of normal [ULN] for the expected normal range for the testing laboratory)

• History of chronic liver disease

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding more than 2.5 times the ULN for the expected normal range for the testing laboratory, not due to HMGCR myopathy.

• Hemoglobin level <9 g/dL

• Known Immunoglobulin A (IgA) deficiency and anti-IgA serum antibodies

• History of chronic alcoholism or illicit drug abuse (addiction) in the prior 12 months

• Active psychiatric illness that interferes with compliance or communication with healthcare personnel

• Currently receiving, or having received, within 1 month prior any investigational medicinal product or device. In the case of an investigational medicinal product trial, at least five half- lives (if known) must have elapsed prior to Screening.

• Any medical condition which makes the clinical trial participation unadvisable or which is likely to interfere with the evaluation of the study treatment and/or the satisfactory conduct of the clinical trial according to the investigator's judgment. Any factor that in the opinion of the investigator would compromise the ability of the subject to complete the trial

• Weight > 120kg. Individuals weighing >100kg and ≤120kg will be eligible at the discretion of the investigators.

• History of angina pectoris or transient ischemic attack (TIA) in the last 12 months

• Wells Criteria Score for DVT of 2 or more at the time of screening.

• Wells Criteria Score for PE of 4 or more at the time of screening.