Clinical trial NCT06868628: A Phase 2a Study of Foralumab Nasal in Patients With Multiple System Atrophy (MSA)
Official title: A Phase 2a Study to Evaluate Microglial Activation, Safety, and Clinical Effects of Foralumab Nasal in Patients With Multiple System Atrophy (MSA)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Multiple System Atrophy
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2025-03-11
Enrollment: 5
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase 2a Study of Foralumab Nasal in Patients with Multiple System Atrophy (MSA)


Eligibility criteria: Inclusion Criteria:

* Subjects with a clinical diagnosis of Clinically Established or Clinically Probable Multiple System Atrophy in accordance with 2022 MDS diagnostic criteria.
* Age 30 to 85 years, at the time of signing the informed consent.
* Stable dopaminergic treatment for at least 4 weeks before enrollment.
* Adequate hematologic parameters without ongoing transfusion support: Hemoglobin (Hb) ≥ 9 g/dL; 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:

* Diagnosis or suspicion of other cause for Parkinsonism or a known alternate neurologic diagnosis.
* Female patient who is pregnant, lactating, breastfeeding, or planning to become pregnant during study.
* Individuals with claustrophobia who cannot tolerate the study procedures
* Non-MRI-compatible implanted devices.
* Low-affinity binders for translocator protein (TSPO) PET ligands.
* Systemic corticosteroid treatment in the past four weeks (excluding nasal or local treatment).
* Individuals with significant cognitive impairment (i.e., MoCA score less than or equal to 20).
* Brain MRI indicative of significant abnormalities that interfere with PET-MRI co-registration (i.e., large prior hemorrhage or multiple infarcts).
* 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), hepatitis C virus (HCV) or positive Epstein-Barr virus (EBV) IgM at the Screening Visit.
* Past medical history of a hematologic or solid malignancy.
* 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.
* Inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren's Syndrome, asthma, or type 1 diabetes.
* Neutropenia or an absolute neutrophil count of \< 1,000 cells/mL or other indicators of severe immunosuppression.
* Severe lymphopenia or an absolute lymphocyte count of \< 500 cells/mL
* Patients with a history of gadolinium allergy.
* A recent clinically significant active infection requiring treatment with antibiotics or other anti-infective agents within the past 15 days.
* Any other medical or surgical 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.
* Active COVID-19 disease.
* COVID-19 vaccine within past 10 days or any other vaccine within past 7 days (at dosing).

Primary outcomes:
measure: Change from Screening to Month 6 in the total MDS-UMSARS score
timeFrame: From Screening to Month 6
measure: Change in TSPO activity as measured by [F-18]PBR06 retention calculated over whole brain and within key regions of interest (ROIs) at 6 months as compared to screening
timeFrame: From Screening to Month 6
Secondary outcomes:
measure: Change from Screening to Month 6 in MDS-UMSARS Part III (motor examination) score
timeFrame: From Screening to Month 6
measure: Proportion of patients with ≥30% improvement in MDS-UMSARS total score at Month 6
timeFrame: From Screening to Month 6
measure: Change from Screening to Month 6 in COMPASS-31 total score
timeFrame: From Screening to Month 6
measure: Change from Screening to Month 6 in MSA-QoL summary index score
timeFrame: From Screening to Month 6
measure: Percent whole brain volume change (PWBVC) between screening and 6 months
timeFrame: From Screening to Month 6
measure: Percent putamen volume change (PPVC) between screening and 6 months
timeFrame: From Screening to Month 6
measure: Percent cerebellar volume change (PCVC) between screening and 6 months
timeFrame: From Screening to Month 6
measure: Percent pontine volume change (PPoVC) between screening and 6 months
timeFrame: From Screening to Month 6
measure: Percent midbrain volume change (PMVC) between screening and 6 months
timeFrame: From Screening to Month 6
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
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