Phase 1b Multiple Ascending Dose Study of Foralumab in Primary and Secondary Progressive MS

NCT05029609 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: TILS-015
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective is to establish the safety of administration of intranasal Foralumab in non-active primary and secondary progressive Multiple Sclerosis (MS) patients in a multiple ascending dose format in escalating doses for 14 consecutive days.

Conditions

Primary Progressive Multiple Sclerosis; Secondary Progressive Multiple Sclerosis; Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• To establish the safety of intranasal foralumab in non-active primary and secondary progressive MS in escalating doses for 14 consecutive days

  Analyses through review of adverse events categorized and graded via CTCAE.

  14 days

Secondary Outcomes (1)

• Change in Expanded Disability Status Scale (EDSS) at Day 45

  45 days

Study Arms (4)

Group A

OTHER

Group A will receive nasal Foralumab Dose 1 daily for 14 days (n=9) or placebo (n=3)

Drug: Intranasal Foralumab Solution; Drug: Placebo

Group B

OTHER

Group B will receive nasal Foralumab Dose 2 tiw for 14 days (n=9) or placebo (n=3)

Drug: Intranasal Foralumab Solution; Drug: Placebo

Group C

OTHER

Group C will receive nasal Foralumab Dose 3 daily for 14 days (n=9) or placebo (n=3)

Drug: Intranasal Foralumab Solution; Drug: Placebo

Group D

OTHER

Group D will receive nasal Foralumab Dose 4 daily for 14 days (n=9) or placebo (n=3)

Drug: Intranasal Foralumab Solution; Drug: Placebo

Interventions

Intranasal Foralumab Solution DRUG

The Aptar Unidose device will be used to deliver foralumab nasal solution intranasally. Foralumab nasal solution is prepackaged in a Type 1 glass vial inside the Unidose device.

Group A; Group B; Group C; Group D

Placebo DRUG

The placebo nasal solution is the acetate buffer vehicle used for foralumab nasal solution. It will be handled in a manner identical to active drug.

Group A; Group B; Group C; Group D

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of MS (according to the 2010 McDonald criteria).
• Age 25-70 years.
• Clinical diagnosis of non-active primary and secondary MS
• MRI imaging consistent with a diagnosis of MS at any time point.
• Score on the Expanded Disability Status Scale (EDSS) of 2.5-6.5
• 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, or \< 5 times ULN for patients with liver metastases
• QT interval corrected for rate (QTcF) ≤ 470 msec for women and ≤ 450 msec for men on the ECG obtained at Screening
• Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP)
• \. Ability to provide written informed consent.

You may not qualify if:

• Corticosteroid use (oral or intravenous) within the last 30 days.
• Current use or use in the prior 6 months of MS immunotherapy, interferon, glatiramer acetate, fingolimod, siponimod, dimethyl fumarate or natalizumab or any other chronic immunosuppressive medication
• Inability to tolerate intranasally administered medications
• Nasal corticosteroids, nasal antihistamines, nasal flu dosing within the past 30 days.
• Chronic rhinitis, deviated septum, nasal polyps, history of sinusitis treated within the past 12 months.
• Active COVID-19 disease; according to FDA guidelines
• 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 (\<500 neutrophils/mL) or other severe immunosuppression
• Unable or unwilling to comply with protocol requirements.
• Patients with a history of gadolinium allergy.
• Screening labs outside of the normal range; EBV IgM positive subjects 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 (See Appendix B) or hereditary long QT syndrome

Sponsors & Collaborators

• Tiziana Life Sciences LTD: lead

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 1b double blind, randomized, placebo controlled, dose escalating study evaluating multiple doses of Foralumab via intranasal administration for 14 days in patients with MS.

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: August 31, 2021
• Study Start: October 1, 2021
• Primary Completion: November 1, 2022
• Study Completion: December 1, 2022
• Last Updated: March 3, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share