Inclusion Criteria:
General Inclusion Criteria (applicable to subjects in all 4 studied indications)
1. Males or female subjects, ≥ 18 years of age at the time of signing informed consent.
2. Ability to understand the requirements of the study.
3. Willingness to provide written informed consent.
4. Willingness to comply with the study protocol procedures.
5. Women of childbearing potential and all male participants must agree to use two
acceptable methods of contraception together to avoid pregnancy. The following are
examples of acceptable methods of contraception including:
1. Established use of oral, inserted, injected, or implanted hormonal methods of
contraception.
2. Correctly placed copper containing intrauterine device (IUD).
3. Male condom or female condom used WITH a spermicide (i.e., foam, gel, film,
cream, suppository).
4. Male sterilization with appropriately confirmed absence of sperm in the
post-vasectomy ejaculate.
5. Bilateral tubal ligation or bilateral salpingectomy.
6. Oral steroids will be tapered to <20 mg/day of prednisone (or equivalent) at least 1
week prior to the first study treatment. The tapering schedule will be at the
discretion of the Investigator.
7. Subjects must have a predicted diffusing capacity for carbon monoxide (DLCO) of >60%
and a forced expiratory volume 1 (FEV1) >70% at screening.
8. Left ventricular ejection fraction (LVEF) ≥ 45% by Echocardiogram. Rituximab and
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9. Baseline laboratory values fulfilling the following requirements to demonstrate
adequate hematologic, renal, and hepatic function:
RA PV MPA / GPA SLE Absolute neutrophil count (/mm3)
- - 1500 Platelets (/mm3)
- 100,000.
- - 75,000 Hemoglobin (g/dL)
- 9.
- - 8 Creatinine clearance (mL/min/1.73 m2)
- 60.
- - 60 Total serum bilirubin (mg/dL) < 2.5 < 2.5 < 2.5 < 2.5 Liver transaminases
(AST/ALT/ALP)
≤ 3x ULN.
≤ 3x ULN.
- - 3x ULN Additional Disease-specific Inclusion Criteria Rheumatoid Arthritis.
1. Documented diagnosis of RA, meeting the 2010 American College of
Rheumatology (ACR)/European League Against Rheumatism (EULAR)
classification criteria for RA (Kay, 2012).
2. Have had prior treatment for a period of at least 12 weeks with a biologic
disease-modifying anti-rheumatic drugs (bDMARD e.g., infliximab,
rituximab, etanercept, tocilizumab)) and/or a targeted synthetic
disease-modifying anti-rheumatic drugs (tsDMARD e.g., baricitinib,
tofacitinib)) and were deemed refractory by either:
1. In the opinion of the Investigator, there was a lack of benefit to at
least two bDMARDs or one bDMARD and one tsDMARDs. Lack of benefit may
include inadequate improvement in joint counts, physical function, or
disease activity.
2. Intolerance to at least two lines of prior therapy, including bDMARDs
and/or tsDMARDs.
3. Minimum of 6 swollen joint counts (SJC) and 6 tender joint counts
(TJC). Pemphigus Vulgaris. 1. Confirmed diagnosis of pemphigus vulgaris with active lesions.
2. Positive for anti-desmoglein Dsg1 or Dsg3.
3. Pemphigus Disease Area Index score of > 10%.
4. Subjects will have tried and failed at least 12 weeks of treatment of
immunosuppressive or biologic standard-of-care agent (methotrexate,
azathioprine, mycophenolate mofetil (MMF) or mycophenolic acid (MPA)
and corticosteroids, and/or 12 weeks of therapy with IV Gamma
globulin treatments with an exposure of 12 weeks to be considered
resistant/refractory and will be included in this study.
Granulomatosis with polyangiitis (GPA) / microscopic polyangiitis
(MPA)
1. Clinical diagnosis of granulomatosis with polyangiitis (GPA) or
microscopic polyangiitis (MPA).
2. Presence of cytoplasmic Antineutrophil cytoplasmic antibody (c-ANCA)
or proteinase-3 (PR3-ANCA) or myeloperoxidase ANCA (MPO-ANCA)
3. Have ≥ 1 "major" item, or ≥ 3 "other" items, or ≥ 2 renal items on
the Birmingham Vasculitis Activity Score Version 3 (BVASv3).
4. For GPA/MPA, subjects will have tried and failed at least 12 weeks of
treatment of immunosuppressive (Cyclophosphamide, mycophenolate
mofetil (MMF) or mycophenolic acid (MPA) and corticosteroids), or a
biologic standard-of-care agent such as Rituximab will be included in
this study.
Systemic Lupus Erythematous. 1. Diagnosis of SLE according to the 2019 European League Against
Rheumatism/American College of Rheumatology (EULAR/ACR)
Classification Criteria.
2. Total systemic lupus erythematosus disease activity index (SLEDAI-2K)
≥ 8 at screening excluding alopecia, mucosal ulcers, and fever.
3. Positive for anti-double-stranded deoxyribonucleic acid (dsDNA)
antibodies.
4. For SLE, subjects will have tried and failed at least 12 weeks of 2
conventional therapies which, at the discretion of the investigator,
includes antimalarials, corticosteroids, immunosuppressive agents,
such as mycophenolate mofetil, Methotrexate, Azathioprine, as well as
biologic agents such as Belimumab, Anifrolumab, and Rituximab.
The following criteria for standard-of-care therapies must be met:
1. If receiving antimalarial drugs (e.g., hydroxychloroquine, chloroquine,
quinacrine), must have used the medication for ≥ 12 weeks prior to first
study treatment and at a stable dose for a minimum of 6 weeks prior to
first administration of AB-101.
2. If receiving immunomodulatory drugs (mycophenolate mofetil
[MMF]/mycophenolic acid ≤ 2 g/day, azathioprine/6 mercaptopurine (AZA/6
MP) ≤ 2 mg/kg/day, leflunomide ≤ 40 mg/day, methotrexate (MTX) ≤ 25 mg/wk
with concomitant folic acid [recommend ≥ 5 mg/wk]), calcineurin inhibitor,
and/or cyclosporin A, receiving a stable dose for at least 12 weeks prior
to the first administration of AB-101.
Oral corticosteroid (OCS) <20 mg/day prednisone or equivalent started at
least 12 weeks prior to first study treatment and at a stable dose for at
least 4 weeks prior to first administration of study treatment. It must be
planned that the background standard-of-care treatment remains at a stable
dose throughout the Screening Period.
Exclusion Criteria:
General Exclusion Criteria (applicable to subjects in all 4 studied
indications) 1. Subjects who received Cyclophosphamide within 3 months 2.
Laboratory values outside the protocol-defined range at screening, unless
the PI documents that the abnormal laboratory value does not compromise
patient safety or interfere with the study's goals.
3. Known hypersensitivity or contraindication to any drug products or
any component of the drug products they plan to receive (e.g.,
cyclophosphamide, fludarabine, rituximab, AB-101).
4. History of an anaphylactic reaction to parenteral administration of
contrast agents, human or murine proteins or monoclonal antibodies or
DMSO (Dimethyl sulfoxide).
5. Prior treatment with any B-cell targeted therapy within 3 months of
the start of the planned lymphodepletion regimen (e.g., rituximab or
other anti-CD20, anti-CD19, anti-CD22 monoclonal antibodies) 6. Prior
treatment with any autologous or allogeneic cell therapy approach
using genetically modified immune cells (e.g., T, NK, macrophages, or
gamma-delta T cells modified with chimeric antigen receptors (CAR)).
7. Received any of the following within 6 months of the start of the
planned lymphodepletion regimen:
1. Immunoglobulin replacement therapies (IV or SC)
2. Plasmapheresis. 8. History of a major organ transplant (e.g., heart, lung,
kidney, liver) or hematopoietic stem cell/marrow transplant, or are due to
receive such transplantation.
9. Known past or current malignancy except for cervical carcinoma of
stage 1B or less, noninvasive basal cell or squamous cell skin
carcinoma, Noninvasive, superficial bladder cancer, Prostate cancer
with a current prostate specific antigen (PSA) level < 0.1 ng/m, Any
curable cancer with a complete response duration of > 2 years 10. Any
history of a B cell malignancy, even if subjects have achieved a
complete response.
11. Known clinically significant cardiac disease: Within the prior 6
months of signing the informed consent form, onset of unstable angina
pectoris or acute myocardial infarction; congestive heart failure
(grade III or IV as classified by the New York Heart Association),
pericarditis present during screening or at baseline, heart
rate-corrected QT interval (QTcF) prolongation > 470 msec at
screening, unless secondary to stable conduction disorders (e.g.,
left bundle-branch block) 12. Unresolved toxicities from prior
therapy, defined as having not resolved to Grade ≤ 1, or to the
levels dictated in the eligibility criteria.
13. Have clinical evidence of significant unstable or uncontrolled acute
or chronic diseases not due to RA, PV, GPA/MPA, SLE (e.g.,
cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic,
renal, neurological, malignancy, or infectious diseases) which, in
the opinion of the principal investigator, could confound the results
of the study or put the subject at undue risk.
14. Have a planned surgical procedure or a history of any other medical
disease (e.g., cardiopulmonary), laboratory abnormality, or condition
(e.g., poor venous access) that, in the opinion of the principal
investigator, makes the subject unsuitable for the study.
15. Have any signs or symptoms of illness/infection or have received any
vaccinations (live or inactivated) within 6 weeks of Day 1.
16. Have current drug or alcohol abuse or dependence, or a history of
drug or alcohol abuse or dependence within ≤ 1 year prior to Day 1.
17. Human immunodeficiency virus (HIV) infection, based on laboratory
testing performed during the screening period.
18. Currently pregnant or lactating (breast feeding must not be started
within 6 months of the last dose of AB-101).
19. Any other considerations that might interfere with the assessment of
safety or efficacy, or that the investigator deems inappropriate for
inclusion.
20. Any medical, psychological, familial, or sociological condition that,
in the Investigator's opinion, would impair the subject's ability to
receive study treatment or comply with study requirements.
21. Severe disease progression or health deterioration within 2 weeks of
Day 1 that, in the opinion of the Investigator, could impair the
ability of the subject to receive study treatment or comply with
study requirements.
22. Known past or current clinically significant lung disease. 23.
History of, or current, chronic pulmonary disease (e.g., COPD,
asthma, etc.) not meeting DLCO and FEV1 eligibility criteria 24.
Pulmonary manifestations of underlying autoimmune disease that may
compromise pulmonary function.
25. History of tobacco exposure of ≥ 5 pack years 26. Subjects with a
prior history of hypogammaglobulinemia or with low IgG levels (< 600
mg/dL). Subjects who have received Intravenous Immunoglobulins (IVIG)
for any reason in the 3 months prior to screening will be excluded.
27. Current use of tobacco product Additional Disease specific Exclusion
Criteria Rheumatoid Arthritis. 1. History of a rheumatologic autoimmune disease other than RA (except
secondary Sjögren's)
2. Significant systemic involvement secondary to RA (e.g., vasculitis,
pulmonary fibrosis, Felty's syndrome)
3. Other arthritis, including Juvenile idiopathic arthritis (JIA) or
idiopathic arthritis diagnosed before the age of 16 years; Psoriatic
Arthritis; Axial spondylarthritis or any other disease associated
with inflammatory arthritis; Active fibromyalgia with pain symptoms
or signs that would interfere with clinical assessments for RA.
Pemphigus Vulgaris. 1. Any condition, including potential flares or new infected or
non-infected lesions that would, in the investigator's judgment,
interfere with full participation in the study.
Granulomatosis with polyangiitis (GPA) / microscopic polyangiitis (MPA) 1.
Any other multi-system autoimmune disease. 2. Have required significant
ongoing management of infections Systemic Lupus Erythematous. 1. Drug-induced lupus.
2. Participants with a history of severe anti-phospholipid syndrome.
