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

February 14, 2022 updated by: Tiziana Life Sciences LTD

A Phase 1b, Double-Blind, Randomized, Placebo Controlled, Multiple Ascending Dose Study of the Safety, Tolerability and Immune Effects of the Intranasal Anti-CD3 Monoclonal Antibody Foralumab in Primary and Secondary Progressive MS

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Up to 55 untreated primary and secondary progressive MS patients will be enrolled, to obtain a total of 48 completed subjects (9 active, 3 placebos per group), allowing for dropouts.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

25 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Confirmed diagnosis of MS (according to the 2010 McDonald criteria).
  2. Age 25-70 years.
  3. Clinical diagnosis of non-active primary and secondary MS
  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. Adequate hematologic parameters without ongoing transfusion support:

    • Hemoglobin (Hb) ≥ 9 g/dL
    • Platelets ≥ 100 x 109 cells/L

  7. 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

  8. Total bilirubin ≤ 2 times the upper limit of normal (ULN) unless due to Gilbert's disease
  9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN, or < 5 times ULN for patients with liver metastases
  10. QT interval corrected for rate (QTcF) ≤ 470 msec for women and ≤ 450 msec for men on the ECG obtained at Screening
  11. Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP)

13. Ability to provide written informed consent.

Exclusion Criteria:

  1. Corticosteroid use (oral or intravenous) within the last 30 days.
  2. 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
  3. Inability to tolerate intranasally administered medications
  4. Nasal corticosteroids, nasal antihistamines, nasal flu dosing within the past 30 days.
  5. Chronic rhinitis, deviated septum, nasal polyps, history of sinusitis treated within the past 12 months.
  6. Active COVID-19 disease; according to FDA guidelines
  7. Female patient who is pregnant, lactating, breastfeeding, or planning on becoming pregnant during study.
  8. Female patients of childbearing age will undergo a pregnancy test and be excluded from the study if positive.
  9. Active malignancy within 5 years.
  10. Inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, asthma, or type 1 diabetes
  11. Neutropenia (<500 neutrophils/mL) or other severe immunosuppression
  12. Unable or unwilling to comply with protocol requirements.
  13. Patients with a history of gadolinium allergy.
  14. Screening labs outside of the normal range; EBV IgM positive subjects with clinical signs will not receive study drug.
  15. 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
  16. 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
  17. Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV)
  18. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Group A
Group A will receive nasal Foralumab Dose 1 daily for 14 days (n=9) or placebo (n=3)
Drug: Intranasal Foralumab Solution
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.
Drug: Placebo
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.
Other: Group B
Group B will receive nasal Foralumab Dose 2 tiw for 14 days (n=9) or placebo (n=3)
Drug: Intranasal Foralumab Solution
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.
Drug: Placebo
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.
Other: Group C
Group C will receive nasal Foralumab Dose 3 daily for 14 days (n=9) or placebo (n=3)
Drug: Intranasal Foralumab Solution
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.
Drug: Placebo
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.
Other: Group D
Group D will receive nasal Foralumab Dose 4 daily for 14 days (n=9) or placebo (n=3)
Drug: Intranasal Foralumab Solution
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.
Drug: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To establish the safety of intranasal foralumab in non-active primary and secondary progressive MS in escalating doses for 14 consecutive days
Time Frame: 14 days
Analyses through review of adverse events categorized and graded via CTCAE.
14 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Expanded Disability Status Scale (EDSS) at Day 45
Time Frame: 45 days
The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. EDSS steps 1.0 to 4.5 refer to people with MS who are able to walk without any aid and is based on measures of impairment in eight functional systems. Lower score indicates that the subject is doing better.
45 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tiziana Life Sciences LTD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 27, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 31, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 3, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 14, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TILS-015

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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