In-patient COVID-19 Study of Intranasal Foralumab

NCT04983446 | Withdrawn Phase 2 DMC

• 1 other identifier: TILS-016
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 2, randomized, placebo-controlled, double-blind, proof-of-concept study of intranasal foralumab in hospitalized subjects with severe COVID-19 and pulmonary inflammation. Foralumab is a fully human second generation anti-CD3 mAb with a modified Fc unit (two amino acid substitutions) composed of 2 heavy chains with an immunoglobulin (Ig) G1constant region and 2 light chains with a kappa constant region. In a separate Phase 2 randomized, controlled, pilot trial conducted to assess safety, tolerability, and efficacy in 39 patients with mild to moderate COVID-19 in Brazil, showed that intranasal foralumab may be of benefit in modulating immune reactivity and in reducing pulmonary inflammation. Importantly, intranasal administration of foralumab was well tolerated with no clinically significant changes in blood cell counts (including blood lymphocytes), no evidence of hypersensitivity, and no serious adverse events (SAEs) were reported in the study.

Conditions

Covid19; COVID-19 Lower Respiratory Infection; COVID-19 Respiratory Infection

Outcome Measures

Primary Outcomes (1)

• To evaluate the effect of intranasal foralumab on evolution of pulmonary infiltrates in hospitalized subjects with severe COVID-19 pneumonia

  It is determined based on change from baseline in semiquantitative chest CT severity score.A chest CT severity score was calculated by assessing the degree of lobe involvement for each of the five lung lobes separately as follows: 0% (no involvement), 1%-25% (minimal involvement), 26%-50% (mild involvement), 51%-75% (moderate involvement), and 76%-100% (severe involvement). Higher the score the worse the outcome.

  Day 14 and Day 28

Secondary Outcomes (3)

• To evaluate the effect of intranasal foralumab on resolution of severe COVID-19 as assessed by chest CT severity score

  Day 14 and Day 28

• To evaluate the safety of intranasal foralumab when administered up to 14 days

  Day 28

• To assess the impact of intranasal foralumab on nasal symptoms when administered up to 14 days

  Day 14

Study Arms (2)

Foralumab Arm + Standard of Care

EXPERIMENTAL

Subjects in this arm would receive, intranasal foralumab 100 µg (50 µg in 0.1 ml solution into each nostril).

Drug: Foralumab

Placebo Arm + Standard of Care

ACTIVE COMPARATOR

Subjects in this arm would receive, placebo (0.1 ml vehicle solution into each nostril).

Other: Placebo

Interventions

Foralumab DRUG

Foralumab is a second generation fully human anti-CD3 antibody

Foralumab Arm + Standard of Care

Placebo OTHER

Placebo will be the vehicle for the foralumab nasal solution without active drug (25 mM sodium acetate/125 mM sodium chloride/0.02% polysorbate 80, pH 5.5 buffer).

Placebo Arm + Standard of Care

Eligibility Criteria

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

You may qualify if:

• Males or females ≥ 18 years of age hospitalized with severe COVID-19, who are within 2 weeks of symptom onset.
• Laboratory-confirmed SARS-CoV-2 infection as determined by nucleic acid amplification test (NAAT) from an upper respiratory specimen within 72 hours of randomization. Test type and result must be documented in the study record.
• Subject agrees to the collection and processing of blood and saliva samples, non-invasive oxygen monitoring (via pulse oximeter), nasal speculum examination, and radiography (high-resolution CT scanning) as required in the protocol.
• Subject (or their legally authorized representative \[LAR\]) is willing and able to provide written informed consent.
• Has at least 2 of the following symptoms for ≥ 48 hours: fever or history of fever (oral temp ≥ 38°C), cough, headache, fatigue, muscle aches, gastrointestinal symptoms, and/or shortness of breath.
• Respiratory rate ≥ 30 per minute, SpO2 ≤ 93% on room air at sea level, heart rate ≥ 125/min, and/or PaO2/FiO2 \< 300.
• Radiologic evidence of pneumonia (infiltrates on high-resolution CT) at screening.
• Erythrocyte sedimentation rate (ESR), CRP and/or lactate dehydrogenase (LDH) \> upper limit of normal \[ULN\] at screening.

You may not qualify if:

• Age \< 18 years.
• Subject has a body mass index \>35 kg/m2 or glycosylated hemoglobin (Hgb A1c) ≥ 9% at screening.
• Currently requires (or in opinion of Investigator is likely to require within 48 hours of enrollment) mechanical ventilation or extracorporeal membrane oxygen saturation (ECMO).
• Prior history (or considered to be at risk) of acute liver disease or chronic unstable liver disease (Child-Pugh B or C) OR alanine transaminase (ALT) or aspartate transaminase (AST) \> 5 × ULN at screening.
• Prior history of chronic obstructive pulmonary disease requiring supplemental oxygen, or active/incompletely treated tuberculosis.
• Concomitant uncontrolled systemic bacterial or fungal infection OR concomitant viral infection other than COVID-19 (e.g., Influenza, respiratory syncytial virus).
• Any underlying condition or therapy associated with immunosuppression.
• Serious concomitant illness which in the opinion of the Investigator precludes the subject from enrolling in the trial.
• History of untreated syphilis, hepatitis B, or untreated hepatitis C virus.
• Uncontrolled human immunodeficiency virus.
• Acute kidney injury Stage 3 or higher or chronic kidney disease Stage 4 or higher.
• Known hypersensitivity to foralumab or excipients.
• Females of child-bearing potential, who are pregnant, breast-feeding, intend to become pregnant or are not using highly effective contraceptive methods. Females who are postmenopausal (defined as at least 12 months of amenorrhea) are not considered to be of child-bearing potential. Highly effective contraceptive methods are defined as:
• Having a male partner who is sterile (vasectomized or orchiectomized) prior to the female subject's entry into the trial and is the sole sexual partner for that female subject
• Surgically sterile (hysterectomy or bilateral oophorectomy); bilateral tubal ligation with surgery at least 6 weeks before study initiation

Sponsors & Collaborators

• Tiziana Life Sciences LTD: lead

MeSH Terms

Conditions

COVID-19

Interventions

foralumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a Phase 2, randomized, placebo-controlled, double-blind, proof-of-concept study of intranasal foralumab in hospitalized subjects with severe COVID-19 and pulmonary inflammation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized 1:1 to receive intranasal foralumab 100 µg (50 µg in 0.1 ml solution into each nostril) or placebo (0.1 ml vehicle solution into each nostril).

Study Record Dates

• First Submitted: July 14, 2021
• First Posted: July 30, 2021
• Study Start: April 30, 2022
• Primary Completion: October 30, 2022
• Study Completion: December 30, 2022
• Last Updated: October 19, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share