Trial Title:
A Study of Nasal Foralumab in Non-Active Secondary Progressive Multiple Sclerosis Patients
NCT ID:
NCT06292923
Condition:
Secondary Progressive Multiple Sclerosis
Conditions: Official terms:
Neoplasm Metastasis
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Conditions: Keywords:
Secondary Multiple Sclerosis
Progressive
Non-active
Double-blind
Nasal Foralumab
Placeb-controlled
Randomized
Phase 2a
Anti-CD3 monoclonal antibody
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Triple (Participant, Care Provider, Investigator)
Masking description:
The treating physician, study staff, and patients will be blinded to treatment. The
research pharmacy at each site will have the treatment code assignments.
Intervention:
Intervention type:
Drug
Intervention name:
Foralumab
Description:
Foralumab nasal solution is a preservative-free, sterile, clear,
colorless-to-slightly-yellow solution filled in an Aptar Unidose nasal atomizer device.
Each Unidose device contains 0.13 mL foralumab placebo nasal solution, sufficient for
administration to a single nare. Two Aptar Unidose devices will be used for a single dose
(one device per nare).
Each Unidose device contains foralumab nasal solution, supplied at either 25 μg foralumab
or 50 μg foralumab, sufficient for administration into a single nare.
Arm group label:
Nasal Foralumab 100 μg
Arm group label:
Nasal Foralumab 50 μg
Intervention type:
Other
Intervention name:
Placebo
Description:
Foralumab placebo nasal solution is a preservative-free, sterile, clear,
colorless-to-slightly-yellow solution filled in an Aptar Unidose nasal atomizer device.
Each Unidose device contains 0.13 mL foralumab placebo nasal solution, sufficient for
administration to a single nare. Two Aptar Unidose devices will be used for a single dose
(one device per nare).
Arm group label:
Nasal placebo (acetate buffer)
Summary:
Foralumab is a human anti-CD3 monoclonal antibody being developed for the treatment of
autoimmune and inflammatory diseases.
The goal of this Phase 2a, randomized, double-blind placebo-controlled, multicenter
dose-ranging study is to evaluate the use of nasal foralumab in patients with non-active
secondary progressive multiple sclerosis (SPMS).
The primary objectives that this study aims to answer are:
1. To determine the safety and tolerability of 50 μg/dose and 100 μg/dose of foralumab
nasal compared to placebo
2. To investigate the effect of foralumab relative to placebo on the change from
baseline [18F]PBR06-positron emission tomography (PET) scans for microglial
activation, after 12 weeks (3) months of study treatment.
Detailed description:
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 hypothsized that nasal foralumab will slow
disability accumulation and microglial activation measured by PET imaging in non-active
SPMS.
This study is a randomized, double-blind, placebo-controlled, multicenter, parallel-group
study of 2 doses of nasal foralumab (50 μg/dose or 100 μg/dose of foralumab nasal)
compared to placebo in the treatment of non-active SPMS for 3 months (4 three-week cycles
of treatment).
Fifty-four subjects with non-active SPMS will be randomized 1:1:1 to one of three
treatment cohorts:
1. Group A: Nasal foralumab 50 μg 3 days a week (Monday-Wednesday-Friday) for two
weeks, followed by a one-week rest, comprising a 3-week cycle, for a total of four
cycles.
2. Group B: Nasal foralumab 100 μg 3 days a week (Monday-Wednesday-Friday) for two
weeks, followed by a one-week rest, comprising a 3-week cycle, for a total of four
cycles.
3. Group C: Nasal placebo (acetate buffer) 3 days a week (Monday-Wednesday-Friday) for
two weeks, followed by a one-week rest, comprising a 3-week cycle, for a total of
four cycles.
Criteria for eligibility:
Criteria:
1. Confirmed diagnosis of MS according to the 2017 McDonald criteria .
2. Age 18 years to age 75 years.
3. Confirmed clinical diagnosis of non-active SPMS, for 2 years prior to the screening
visit. The baseline study visit and/or the baseline MRI may not be used to confirm
the diagnosis but will be used to establish a study baseline and for interpretation
of the PET scan data. The second qualifying MRI must be within 3 months of the study
screening MRI.
4. MRI imaging consistent with a diagnosis of MS at any time point.
5. Score on the Expanded Disability Status Scale (EDSS) of 2.5-6.5.
6. Have failed standard-of-care treatment with disease-modifying therapies for at least
2 years with continued accumulation of disability as evaluated by treating
neurologist. Treatment failure/progression can be defined as EDSS worsening despite
best treatment efforts:
- EDSS increase by 1.0 (if baseline EDSS between 1.0-5.5) in the past 2 years.
- EDSS increase by 0.5 (if baseline EDSS >6.0) in the past 2 years.
7. Screening clinical laboratory studies are within the normal ranges or within the
parameters specified below, and clinically acceptable in the opinion of the
Investigator. Exceptions must be approved by the CRO or Sponsor's Medical Monitor.
- Adequate hematologic parameters without ongoing transfusion support:
- Hemoglobin (Hb) ≥9 g/dL
- Platelets ≥100 × 10^9 cells/L
- Creatinine ≤1.5 × the upper limit of normal (ULN), or calculated creatinine
clearance ≥60 mL/minute × 1.73 m^2 per the Cockcroft-Gault formula.
- Total bilirubin ≤1.5 times the upper limit of normal (ULN) unless due to
Gilbert's disease.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.0 times
ULN.
8. Negative serum pregnancy test at screening and negative urine pregnancy test within
7 days prior to the first dose of study therapy for women of child-bearing
potential, 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).
9. Sexually active women of child-bearing potential and male patients must agree to use
2 effective methods to avoid pregnancy (oral, injectable, or implantable hormonal
contraceptives; 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.
10. Immunizations are current and up-to-date as adjusted for disease status and
prior/current treatments, and documented by the patient's treating neurologist.
11. Ability and willingness to provide written informed consent.
Exclusion Criteria:
1. Corticosteroid use (oral or intravenous) within the last 60 days or anticipated need
for such treatment during the study period.
2. Current use or use within 30 days prior to the screening visit of interferon,
glatiramer acetate, fingolimod, siponimod, dimethyl fumarate, ponesimod, ozanimod,
cyclosporin, methotrexate, azathioprine, mycophenolate mofetil, natalizumab or any
other chronic immunosuppressive medication. Concomitant immunomodulatory or
immunosuppressant treatments for MS are not permitted during study participation.
3. Patient in whom the need to start or stop other pharmacologic treatment for MS is
expected during the time of the study or the need for initiation of B cell depleting
therapies (e.g. ocrelizumab, ofatumumab, rituximab) during the study.
4. Use of B cell depleting therapies (e.g. ocrelizumab, ofatumumab, rituximab) within
the prior 6 months. Or use of terifluonimide within the previous 6 months.
5. Patients with any previous exposure to alemtuzumab, cyclophosphamide, cladribine,
mitoxantrone, or daclizumab.
6. Prior use of AHSCT or stem cell therapy.
7. Inability to tolerate nasally administered medications.
8. Nasal corticosteroids, nasal antihistamines, nasal flu dosing within the past 60
days.
9. Active COVID-19 disease; according to FDA guidelines.
10. Female patient who is pregnant, lactating, breastfeeding, or planning on becoming
pregnant during the study. Female patients of childbearing age will undergo a serum
pregnancy test at screening and be excluded from the study if positive. Urine
pregnancy testing will be carried out prior to each dosing cycle, and the patient's
study participation will be stopped if there is a positive result. Pregnancy testing
will also be performed prior to each MRI or PET imaging session and participation in
the imaging session and the study will be terminated if positive.
11. Any history of malignancy or active malignancy.
12. Inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus,
asthma, or type 1 diabetes.
13. Patients with a history of gadolinium allergy or any other contraindications to MRI,
such as metal implants, chronic renal disease, and an eGRF of <30 mL/minute or
claustrophobia, or who are unable to lay flat in the PET or MRI scanner for the
duration of the studies.
14. A low affinity translocator protein (TSPO) binder (for PET ligand [18F]PBR06)
determined by having a Thr/Thr polymorphism in the TSPO gene at screening.
15. EBV IgM-positive patients, assessed at screening. Patients will also be excluded if
they have a documented history of being EBV positive, even if the testing at
screening is negative.
16. Known positivity for human immunodeficiency virus (HIV), hepatitis B virus surface
antigen (HBsAg), or hepatitis C virus (HCV) or tuberculosis at screening. If the
patient has a history of positivity for any of these diseases, they are excluded
even if current screening is negative.
17. Patients with a neutrophil count at baseline of <1000 cells/mL or lymphocytes <500
cells/mL.
18. Any nasal pathology such as clinically significant deviated septum, nasal polyps,
chronic rhinitis, or a history of sinusitis diagnosed or treated in the past 12
months.
19. Clinically significant cardiac condition or ECG abnormality at screening or by
history. An ECG will be done prior to each dosing cycle and patients will be
excluded or treatment discontinued for any significant ECG abnormality.
20. 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.
21. A history of recent infections or treatment for infections.
22. Receipt of an investigational drug/biological product in the past 30 days of
screening, or concurrent receipt of an investigational during this study, other than
the product under study. Patients may not have previously received treatment with
foralumab nasal.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Recruiting
Contact:
Last name:
Niveditha Gopalakrishnan
Phone:
617-732-5588
Email:
foralumab@mgb.org
Investigator:
Last name:
Tanuja Chitnis, M.D
Email:
Principal Investigator
Start date:
November 15, 2023
Completion date:
November 2024
Lead sponsor:
Agency:
Tiziana Life Sciences LTD
Agency class:
Industry
Source:
Tiziana Life Sciences LTD
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06292923
