Covid19Phase 2NCT04983446
In-patient COVID-19 Study of Intranasal Foralumab
A Phase 2 study testing Foralumab in people with Covid19 and COVID-19 Lower Respiratory Infection, run by Tiziana Life Sciences LTD.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, COVID-19 Lower Respiratory Infection, COVID-19 Respiratory Infection
- What is being tested?
- Foralumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Apr 2022to 30 Dec 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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
- Use of intra-uterine devices in place for at least 3 months
- Stable hormonal contraception for at least 3 months before study initiation and through study completion
- Barrier method (condom or diaphragm) with spermicide for at least 14 days before study initiation through study completion
- True abstinence: When this is in line with the preferred and usual lifestyle of the subject (period abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
- Active participation in any other clinical trial or receipt of an experimental treatment within the preceding 30 days.
- Receipt of COVID-19 convalescent plasma, or COVID-19 mAbs, within 3 months of enrollment.
- Receipt of any anti-IL-6 mAb or similar anti-inflammatory medications (e.g, Janus kinase inhibitors) within 3 months of enrollment.
- Prior receipt of any COVID-19 vaccine.
- Receipt of any treatment for COVID-19 (off-label, compassionate use, or investigational use) except per local SoC within 30 days prior to screening.
- History of opioid or cocaine (including crack cocaine) use.
- Use of any nasally administered medications within 1 week of enrollment.
- In the opinion of the Investigator, the subject is unable to comply with the requirements to participate in the study.
About this study
Official title: A Phase 2 Proof-of-concept Study to Evaluate the Safety, Tolerability, and Efficacy of Intranasal Foralumab in Hospitalized Subjects With Severe COVID-19 and Pulmonary Inflammation
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.
Read the detailed description
Approximately 80 hospitalized subjects with severe COVID-19 and evidence of pulmonary involvement on a computed tomography (CT) scan at screening will be enrolled in this study over 4 months, depending on enrollment. Up to 7 centers in Brazil will conduct this study.
The main study objective is to evaluate the effect of intranasal foralumab on evolution of pulmonary infiltrates in hospitalized subjects with severe COVID-19 pneumonia.
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). All subjects will receive continued Standard of Care (SoC) therapy (per hospital/study site policies and guidelines) together with intranasal foralumab or placebo for the entire 14-day treatment period.
Subjects will participate in the study approximately 35 days (from screening to completion).
- Being tested
- Foralumab, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ForalumabDrug
Foralumab is a second generation fully human anti-CD3 antibody
PlaceboOther
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).
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Foralumab |
| Placebo Arm + Standard of Care | Active comparator | Subjects in this arm would receive, placebo (0.1 ml vehicle solution into each nostril). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Proportion of randomized subjects with chest CT severity score < 19.5
Measured: Day 14 and Day 28
To evaluate the safety of intranasal foralumab when administered up to 14 days
Adverse events categorized and graded via CTCAE
Measured: Day 28
To assess the impact of intranasal foralumab on nasal symptoms when administered up to 14 days
Change from baseline in subject-reported Intranasal Tolerability Rating Scale (ITRS). ITRS is rated on an 11-point scale, ranging from 0 (none) to 10 (worst I can imagine) and consists of 3 questions.
Measured: Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2021
- Study start30 Apr 2022 (estimated)
- Primary completion30 Oct 2022 (estimated)
- Study completion30 Dec 2022 (estimated)
Why it stopped: Withdrawn due to business reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tiziana Life Sciences LTD
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04983446
- Sponsor's protocol ID
- TILS-016
- Status last verified
- Oct 2022
- First submitted
- 14 Jul 2021
- Last updated
- 19 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Proof-of-concept Study to Evaluate the Safety, Tolerability, and Efficacy of Intranasal Foralumab in Hospitalized Subjects With Severe COVID-19 and Pulmonary Inflammation
- ClinicalTrials.gov ID
- NCT04983446
- Acronym / sponsor ID
- TILS-016
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawn due to business reasons
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Tiziana Life Sciences LTDIndustry (pharma, biotech, devices)
- Study start
- 30 Apr 2022 (estimated)
- Primary completion
- 30 Oct 2022 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 30 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Approximately 80 hospitalized subjects with severe COVID-19 and evidence of pulmonary involvement on a computed tomography (CT) scan at screening will be enrolled in this study over 4 months, depending on enrollment. Up to 7 centers in Brazil will conduct this study.
The main study objective is to evaluate the effect of intranasal foralumab on evolution of pulmonary infiltrates in hospitalized subjects with severe COVID-19 pneumonia.
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). All subjects will receive continued Standard of Care (SoC) therapy (per hospital/study site policies and guidelines) together with intranasal foralumab or placebo for the entire 14-day treatment period.
Subjects will participate in the study approximately 35 days (from screening to completion).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Foralumab Arm + Standard of Care | Experimental | Drug: ForalumabSubjects in this arm would receive, intranasal foralumab 100 µg (50 µg in 0.1 ml solution into each nostril). |
| Placebo Arm + Standard of Care | Active comparator | Other: PlaceboSubjects in this arm would receive, placebo (0.1 ml vehicle solution into each nostril). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ForalumabForalumab is a second generation fully human anti-CD3 antibody | Drug | Foralumab Arm + Standard of Care |
| PlaceboPlacebo 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). | Other | Placebo Arm + Standard of Care |
Primary outcome
To evaluate the effect of intranasal foralumab on evolution of pulmonary infiltrates in hospitalized subjects with severe COVID-19 pneumonia
Time frame: Day 14 and Day 28
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.
3 secondary outcomes
To evaluate the effect of intranasal foralumab on resolution of severe COVID-19 as assessed by chest CT severity score
Time frame: Day 14 and Day 28
To evaluate the safety of intranasal foralumab when administered up to 14 days
Time frame: Day 28
To assess the impact of intranasal foralumab on nasal symptoms when administered up to 14 days
Time frame: Day 14
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Foralumab in people with Covid19 and COVID-19 Lower Respiratory Infection, run by Tiziana Life Sciences LTD.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the effect of intranasal foralumab on evolution of pulmonary infiltrates in hospitalized subjects with severe COVID-19 pneumonia (time frame: Day 14 and Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2022.