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

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.

Study Overview

• Status: Withdrawn
• Conditions: Immune-Mediated Necrotizing Myopathy
• Intervention / Treatment: Drug: Gamunex-C; Drug: Albumin

Detailed Description

This is a phase 2, double-blinded, randomized, placebo-controlled, multi-center trial of Gamunex-C IVIG as mono-therapy for HMGCR necrotizing myopathy. Up to 10 treatment-naïve patients will be enrolled and randomized to receive either Gamunex-C IVIG dosed at 2g/kg or placebo at week 0 and week 4. The primary efficacy outcome is the percentage of patients at week 8 with at least minimal improvement per the 2016 ACR/EULAR myositis clinical response criteria.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.
• Participants taking oral or intravenous glucocorticoids where the dose has changed within 4 weeks of screening.
• 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
• Currently taking a statin medication
• 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., estimated glomerular filtration rate (eGFR) below 60ml/min)
• 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.
• Presence of a central, in-dwelling catheter (such as a PICC line) at the time of informed consent.
• Currently taking a nephrotoxic drug (eg gentamicin or vancomycin) at the time of informed consent.
• Severe cardiac failure at the time of informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gamunex-C IVIG; Gamunex-C IVIG dosed at 2g/kg will be given on week 0 and week 4.	Drug: Gamunex-C; Gamunex-C IVIG will be given at week 0 and week 4; Other Names: IVIG
Placebo Comparator: Placebo; Albumin in a 1% solution at an equivalent volume to the corresponding Gamunex-C IVIG dose will be given at week 0 and week 4.	Drug: Albumin; 1% albumin solution dosed at equivalent volume to the corresponding weight-based Gamunex-C IVIG dose will be given at week 0 and week 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR/EULAR 2016 Clinical Response Criteria for Myositis	The percentage of patients in each arm with at least a minimal response	week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Manual Muscle Strength Testing (MMT-8) score	Manual muscle strength testing in 8 muscle groups will be scored. Range 0-160, with higher scores reflecting increased muscle strength.	week 8
ACR/EULAR Clinical Response Criteria for Myositis Total Improvement Score	The total improvement score based on ACR/EULAR 2016 criteria will be calculated. Range 0-100, with higher scores reflecting greater improvement.	week 8
HMG-CoA Reductase Auto-antibody titer level	Autoantibody titer level will be assessed	week 8
Creatine kinase	Serum creatine kinase level will be measured	week 8
Number of patients screened to achieve planned enrollment		2 years
Number of days needed to enroll planned sample		2 years
Percentage of enrolled patients completing all primary and secondary measures		2 years

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Grifols Biologicals, LLC
• Investigators: Principal Investigator: James S Andrews, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2022
• Primary Completion (Actual): July 25, 2022
• Study Completion (Actual): July 25, 2022

Study Registration Dates

• First Submitted: June 24, 2020
• First Submitted That Met QC Criteria: June 24, 2020
• First Posted (Actual): June 29, 2020

Study Record Updates

• Last Update Posted (Actual): October 24, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: HMG-CoA Reductase Auto-Antibody Necrotizing Myopathy
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Muscular Diseases; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins, Intravenous
• Other Study ID Numbers: STUDY00009143

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No