This is an open-label, intermediate-size patient population expanded access treatmentstudy utilizing 1 dose level of nasal Foralumab (50 µg/dosing day) with the possibilityof increasing to 100 µg/dosing day. The goal of this expanded access clinical trial is toevaluate safety, tolerability, and immune effects of intranasal Foralumab in non-activesecondary progressive multiple sclerosis patients. The primary objective is to treatpatients who have failed current available therapy. Participants will visit the clinicfor testing and follow-up every cycle (3 weeks) while administering the medication athome if able three times weekly.
Multiple sclerosis (MS) is a common autoimmune disorder affecting young adults, driven by
an aberrant T cell response against central nervous system (CNS) antigens. Epidemiologic
studies show that approximately 50% of patients are classified as having
relapsing-remitting multiple sclerosis (RRMS), while about 35% have SPMS and the
remaining 15% have primary progressive MS (PPMS).
Foralumab is a human anti-CD3 monoclonal antibody being developed for the treatment of
autoimmune and inflammatory diseases. It is hypothesized that nasal Foralumab will slow
disability accumulation and microglial activation measured by PET imaging in non-active
SPMS.
Patients will be dosed in 3-week cycles, with Foralumab dosing on Days 1, 3 and 5 of the
first and second weeks, followed by a "rest week". This study will assess the safety of
nasal Foralumab given over 6 months to non-active secondary progressive MS patients who
have failed currently available treatments including the standard of care therapy,
Ocrevus (ocrelizumab).
Drug: Foralumab TZLS-401 50 µg
Foralumab 50 µg/dosing day for patients who have failed current therapies. Patients will
be dosed in 3-week cycles, with foralumab dosing on Days 1, 3 and 5 of the first and
second weeks, followed by a "rest week". Patients will receive Day 1 doses of nasal
foralumab under supervision at the Center for Clinical Investigation at BWH.
Inclusion Criteria:
- Confirmed diagnosis of MS (according to the 2010 McDonald criteria).
- Age 25-75 years old.
- Clinical diagnosis of non-active SPMS, as defined by the absence of relapses for 2
years.
- MRI imaging consistent with a diagnosis of MS at any time point.
- Score on the Expanded Disability Status Scale (EDSS) of 2.5-7.5.
- Have failed standard of care treatment and continued to decline clinically for at
least 6 months.
- Adequate hematologic parameters without ongoing transfusion support:
1. Hemoglobin (Hb) ≥ 9 g/dL
2. Platelets ≥ 100 x 109 cells/L
- Creatinine ≤ 1.5 x the upper limit of normal (ULN), or calculated creatinine
clearance ≥ 60 mL/minute x 1.73 m2 per the Cockcroft-Gault formula.
- Total bilirubin ≤ 2 times the upper limit of normal (ULN) unless due to Gilbert's
disease.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN.
- QT interval corrected for rate (QTcF) ≤ 470 msec for women and ≤ 450 msec for men on
the ECG obtained at Screening
- Negative urine pregnancy test within 7 days prior to the first dose of study therapy
for women of child-bearing potential (WCBP), defined as a sexually mature woman who
has not undergone a hysterectomy or who has not been naturally postmenopausal for at
least 24 consecutive months (i.e., who has had menses any time in the preceding 24
consecutive months). Sexually active WCBP and male patients must agree to use highly
effective methods to avoid pregnancy (oral, injectable, or implantable hormonal
contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with
spermicide; or vasectomized partner) throughout the study and for 90 days after the
completion of study treatment.
- Patients whose immunizations are fully up to date at the Screening, according to the
assessment of their primary care physician and neurologist.
- Ability to provide written informed consent.
Exclusion Criteria:
- Need for corticosteroid treatment (oral or intravenous) within the past 30 days or
anticipated need within 30 days of foralumab therapy initiation.
- Treatment with Ocrevus® (ocrelizumab), Rituxun® (rituximab), Kesimpta® (ofatumumab),
Truxima® (rituximab-abbs) within the past 90 days.
- Treatment with Lemtrada® (alemtuzumab) and Mavenclad® (cladribine) within the past 1
year.
- Treatment with chronic immunosuppressives such as interferon, glatiramer acetate,
fingolimod, siponimod, dimethyl fumarate or natalizumab within the past 90 days.
- Inability to tolerate nasally administered medications.
- Nasal corticosteroids, nasal antihistamines, nasal flu dosing within the past 30
days, or anticipated need during the study.
- Chronic rhinitis, deviated septum, nasal polyps, history of sinusitis treated within
the past 8 months.
- Active COVID-19 disease.
- COVID-19 vaccine within past 10 days or any other vaccine within past 7 days (at
dosing).
- Female patient who is pregnant, lactating, breastfeeding, or planning on becoming
pregnant during study.
- Female patients of childbearing age will undergo a pregnancy test and be excluded
from the study if positive.
- Active malignancy within 5 years.
- Inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus,
asthma, or type 1 diabetes.
- Neutropenia or an absolute neutrophil count of < 1,000 cells/mL or other indicators
of severe immunosuppression.
- Patients with a history of gadolinium allergy.
- Screening labs outside of the normal range; EBV IgM positive patients with clinical
signs will not receive study drug.
- Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia,
myocardial infarction, unstable angina, or heart disease defined by the New York
Heart Association (NYHA) Class III or Class IV or hereditary long QT syndrome.
- Concomitant medication(s) that may cause QTc prolongation or induce Torsades de
Pointes, except for antimicrobials that are used as standard of care to prevent or
treat infections and other such drugs that are considered by the Investigator to be
essential for patient care.
- Patients who test positive for human immunodeficiency virus (HIV), hepatitis B virus
surface antigen (HBsAg), or hepatitis C virus (HCV) at the Screening Visit.
- A recent clinically significant active infection requiring treatment with
antibiotics or other anti-infective agents within the past 15 days.
- Patients whose immunizations are not fully up to date at the Screening Visit, as
assessed by their primary care physician and neurologist.
- Any other medical intervention or other condition which, in the opinion of the
Principal Investigator, could compromise adherence to study requirements or confound
the interpretation of study results.
- Unable or unwilling to comply with protocol requirements.
Brigham and Women's Hospital
Boston, Massachusetts, United States
Investigator: Research Coordinator
Contact: 6177325588
foralumab@mgb.org
William Clementi, PharmD FCP
1-833-849-4262
ms@tizianalifesciences.com
Keeren Shah
1-833-849-4262
ms@tizianalifesciences.com
Not Provided