Personalized Immunotherapeutic for Antibiotic-resistant Infection

Study Overview
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Brief Summary
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M. A. suffers from hypogammaglobulinemia that has been complicated by refractory Mycoplasma hominis septic arthritis. He has been receiving the antibiotic valnemulin under Emergency Investigational New Drug (eIND) 114686 following many prior treatments with standard antibiotics. M.A. has also been receiving intravenous immunoglobulin (IVIG) replacement. The antibiotic and IVIG have been helpful, but not sufficient for cure. Antibodies have been shown to be critical for defense against mycoplasma. Hyperimmune serum against mycoplasma isolated from rabbit or goat has been effective in cases of chronic erosive arthritis in the setting of immune deficiency, and in some cases resulted in cures. The investigators propose to use M. hominis isolated from M. A. to vaccinate one transgenic cow (developed by SAB Biotherapeutics), purify human antibody after vaccination, test the purified antibody in killing assays to confirm potency, and then administer the purified human IgG to M. A. after FDA compassionate use IND application and local Institutional Review Board (IRB) approval.

Detailed Description
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M. A. suffers from hypogammaglobulinemia that has been complicated by refractory Mycoplasma hominis septic arthritis. He has been receiving the antibiotic valnemulin under Emergency Investigational New Drug (eIND) 114686 following many prior treatments with standard antibiotics. M.A. has also been receiving intravenous immunoglobulin (IVIG) replacement. The antibiotic and IVIG have been helpful, but not sufficient for cure. Antibodies have been shown to be critical for defense against mycoplasma. Hyperimmune serum against mycoplasma isolated from rabbit or goat has been effective in cases of chronic erosive arthritis in the setting of immune deficiency, and in some cases resulted in cures. SAB Biotherapeutics, Inc. (formerly Sanford Applied Biosciences, LLC) located in Sioux Falls, SD, have developed transchromosomic (Tc) cows containing human immunoglobulin (Ig) heavy (IgH) and light (IgL) chain loci in the setting of inactivated bovine IgH and Ig lambda loci. To date, SAB Biotherapeutics (SAB) has several products in development that have been tested in animal models, but to date no human trials. Investigators propose to use M. hominis isolated from M. A. to vaccinate one transgenic cow, purify antibody after vaccination, test the purified antibody in killing assays to confirm potency, and then administer the purified human IgG to M. A. after FDA compassionate use IND application and local Institutional Review Board (IRB) approval. M. A. is a highly educated person with full decision making capacity and is well aware of the uncertainties and risks associated with this treatment. This proposal is designed to offer this patient an alternative and perhaps curative approach to his disease.

Official Title
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Personalized Immunotherapeutic for Antibiotic-resistant Infection

Conditions
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Infection, Immune Deficiency, Hypogammaglobulinemia, Septic Arthritis, Mycoplasma Hominis

Intervention / Treatment
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* Biological: anti-mycoplasma hominis antibodies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult with decision making capacity afflicted with chronic mycoplasma hominis septic arthritis despite standard treatments. Exclusion Criteria: None
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>This is a single patient treatment IND | Biological: anti-mycoplasma hominis antibodies<br>* provision of customized anti-mycoplasma hominis antibodies in the context of a treatment IND.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence or absence of mycoplasma hominis cultured from joint and wound fluid | see publication below | from date of initiation of therapy up to 1 year | 
| Patency of fistula as assessed by clinical exam | see publication below | from date of initiation of therapy up to 1 year | 
| Pain reduction as measured by pain scale and amount of pain medication required | see publication below | from date of initiation of therapy up to 1 year |