COVID-19Phase 2/3NCT04586153
Study to Assess the Effect of Meplazumab on COVID-19
A Phase 2/3 study testing Meplazumab for Injection and Sterile normal saline (0.9%) in people with COVID-19, run by Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd at 1 site in Brazil.
Trial summary
This phase2/3 study will be conducted to evaluate the safety and efficacy of Meplazumab in addition to Standard of Care for the treatment of Corona Virus Disease(COVID) 19 in hospitalized adults Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Meplazumab for Injection and Sterile normal saline (0.9%)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 174 participants
- Where
- 1 siteBrazil
- Study dates
- 15 Feb 2021to 18 Dec 2022
- Phase
- Phase 2/3
- 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
- Adults (≥18 years) with laboratory-confirmed SARS CoV 2 infection as determined by PCR or other commercial or public health assay, which is FDA cleared or approved for emergency use (test results must be obtained within 72 hours of Day
- A score of Grade 3 (hospitalized, requiring supplemental oxygen) or Grade 4 (hospitalized, on non-invasive ventilation or high flow oxygen devices) on the 6-point ordinal scale.
- Willingness and ability to comply with study-related procedures and assessments.
- Ability to provide informed consent signed by study subject or legally authorized representative.
- Male and/or female
- a)Male subjects:
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- A male subject must agree to use contraception as detailed in Appendix 12.3 of this protocol during the treatment period and for at least 6 months, corresponding to time needed to eliminate study treatment for both genotoxic and teratogenic study treatments, after the last dose of study treatment.
- b)Female subjects:
- A female subject is eligible to participate if she is not pregnant (see Appendix 12.3), not planning to get pregnant in the next 6 months, not breastfeeding, and at least 1 of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 12.3. OR ii) A WOCBP who agrees to follow the contraceptive guidance in Appendix 12.3 during the treatment period and for at least 130 days, (5 terminal half lives and, for genotoxic products, an additional 30 days, corresponding to time needed to eliminate study treatment plus 30 days for study treatments with genotoxic potential) after the last dose of study treatment.
Who cannot join
- Any physical examination findings, laboratory abnormality, and/or history of any illness, that in the study Investigator's judgment, could jeopardize the safety of the subject by their participation in the study.
- Subjects with evidence of critical COVID 19 illness, defined by at least 1 of the following: respiratory failure; shock (defined by systolic blood pressure <90 mm Hg, or diastolic blood pressure <60 mm Hg, or requiring vasopressors); or multi-organ dysfunction/failure.
- Subjects requiring extracorporeal membrane oxygenation (ECMO).
- Stage 4 severe chronic kidney disease or requiring dialysis (ie, estimated glomerular filtration rate(eGFR) mL/min/1.73 m2 < 30).
- Pregnant or breast feeding.
- Anticipated transfer to another hospital which is not a study site within 72 hours.
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- Allergy to any study medication.
- Use of anticancer, antitransplant rejection, or immunomodulatory biological drug or kinase inhibitor (eg, tocilizumab, sarilumab) or Janus kinase inhibitors (within 30 days of enrollment or 5 times the half-life [whichever is longer]).
- Chronic glucocorticosteroid use equivalent to daily oral prednisone >10 mg per day (10 mg oral prednisone every other day is allowed).
- Live (live-attenuated) vaccines are not permitted within 2 weeks prior to randomization or during the study treatment and safety follow-up periods.
- Subjects participating in another clinical study. There will be a need for washout with 5 half lives depending on the study treatment or 30 days since any previous study, whichever is longer.
- Total bilirubin (TBL) >2 × upper limit of normal (ULN), or alanine aminotransferase (ALT) >5 × ULN, or aspartate aminotransferase (AST) >5 × ULN, or alkaline phosphatase >5 × ULN.
- Platelet <50×109/L, or hemoglobin <60g/L.
- Glomerular filtration rate <30 milliliter(mL)/min/1.73 m2, or serum creatinine increased by 0.5 mg/dL within 7 days, or oliguria (<400 mL/24 hour), or anuria (<100 mL/24 hour).
- Any physical examination findings, laboratory abnormality, and/or history of any illness, that in the study Investigator's judgment, could jeopardize the safety of the subject by their participation in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicenter, Seamless, Randomized, Third-Party-Blind, Clinical Trial to Evaluate the Safety and Efficacy of Meplazumab in Addition to Standard of Care for the Treatment of COVID-19 in Hospitalized Adults
This phase2/3 study will be conducted to evaluate the safety and efficacy of Meplazumab in addition to Standard of Care for the treatment of Corona Virus Disease(COVID) 19 in hospitalized adults
Read the detailed description
- Rationale: Meplazumab is a humanized anti-CD147 immunoglobulin 2 (IgG2) monoclonal antibody which is expected to block the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein to the human host-cell-expressed CD147, thereby blocking entry of SARS-CoV-2 into human tissue. This expectation is based on in vitro functional studies using Vero E6 cells infected with SARS-CoV-2 that demonstrated effective meplazumab mediated virus gene copy number inhibition upwards of 90% as evaluated by quantitative polymerase chain reaction. Meplazumab may also inhibit COVID-19 associated cytokine storm syndrome based on inhibition of the pro inflammatory factor Cyclophilin A host-cell CD147 interaction.
- Overall Design: This is a multicenter, seamless, randomized, third-party-blind, study to evaluate the safety and efficacy of meplazumab for the treatment of COVID 19 in hospitalized adults (≥18 years). Neither the subject nor the investigator shall be aware of the study drug identity, as the study drug is dispensed by a third party (eg, a pharmacist or nurse). Enrollment of subjects will be stopped once the total number of planned subjects have completed the Stage 1 Day 29 visit procedures. Once the interim analysis of Stage 1 study data is complete and the Independent Data Monitoring Committee (IDMC) has recommended the meplazumab dose that is safe and effective to carry forward into Stage 2, the study will resume subject enrollment. A summary of the key Stage 1 interim analysis results will be sent to the relevant Health Authorities involved, if requested.
- Number of Investigators and Study Centers: There will be 15 to 20 Investigators, at 12 to 20 study centers globally, participating in this study.
- Number of Subjects: Subjects will be screened 1 day before randomization. Stage 1: Approximately 168 subjects will be randomized and allocated 1:1:1:1 (42:42:42:42) to receive meplazumab low dose, meplazumab medium dose, meplazumab high dose, or control. An interim analysis will be conducted to select the optimal dose of meplazumab compared with the control group based on response rates of clinical improvement at Day 29. Stage 2: 276 more subjects will be randomized and allocated 1:1 (138:138) to receive 0.2mg/kg meplazumab or control. At interim analysis, primary endpoint, sample size calculation for Stage 2 will be re evaluated based on the observed outcomes at Stage 1 and will be capped at 300 subjects total.
- Treatment Groups and Duration:
Study duration for each subject will be 84±7 days from randomization in each stage.
- Conditions
- COVID-19
- Being tested
- Meplazumab for Injection, Sterile normal saline (0.9%)
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Meplazumab for InjectionDrug
humanized antibody target CD147
Sterile normal saline (0.9%)Drug
Sterile normal saline (0.9%)
| Study group | Role | What they receive |
|---|---|---|
| Meplzaumb | Experimental | This arm is combined with 3 groups, low dose, middle dose, and high dose. Low dose group: First dose: 0.12 mg/kg - Day 1; second dose: control - Day 8 Middle dose group: First dose: 0.2 mg/kg - Day 1; second dose: 0.2 mg/kg - Day 8 High dose group: First dose: 0.3 mg/kg - Day 1; second dose: 0.3 mg/kg - Day 8 Receives: Drug: Meplazumab for Injection |
| Placebo | Placebo comparator | First dose: control - Day 1; second dose: control - Day 8 Receives: Drug: Sterile normal saline (0.9%) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality (based on the interim analysis of Stage 1 data)
Mortality (based on the interim analysis of Stage 1 data)
Measured: During the evaluation period (Day 1 to Day 29)
Proportion of subjects alive and discharged without supplemental oxygen
To evaluate live discharge
Measured: During the evaluation period (Day 1 to Day 29)
Secondary outcomes (3)
Changes from baseline in cytokine, chemokines and related inflammatory factors.
To evaluate pharmacodynamic (PD) response to administration of meplazumab, including cytokine, chemokines and related inflammatory factors (IL-2、IL-4、IL-6、IL-7、IL-8、IL-10、IL-12p70、IL-15、IL-17A、IL-1RA、IL-2Rα、MCP-1、MIP-1β、IP-10、TNFα、IFN-γ).
Measured: During the evaluation period (Day 1 to Day 29)
Viral load
Changes from baseline in viral load. Viral load will be determined by qPCR for COVID-19 in nasopharyngeal swab.
Measured: During the evaluation period (Day 1 to Day 29)
Viral negative rate of SARS-Cov-2 nucleic acid
Viral negative rate of SARS-Cov-2 nucleic acid.
Measured: During the evaluation period (Day 1 to Day 29)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2020
- Study start15 Feb 2021
- Primary completion2 Dec 2022
- Study completion18 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 174 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04586153
- Sponsor's protocol ID
- MPZ-II-02
- Status last verified
- May 2022
- First submitted
- 12 Oct 2020
- Last updated
- 15 Sep 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Bian H, Chen L, Zheng ZH, Sun XX, Geng JJ, Chen R, Wang K, Yang X, Chen SR, Chen SY, Xie RH, Zhang K, Miao JL, Jia JF, Tang H, Liu SS, Shi HW, Yang Y, Chen XC, Malhotra V, Nasir N, Khanum I, Mahmood F, Hamid S, Stadnik CMB, Itinose K, de Oliveira CCC, Dusilek C, Rivabem L, Cavalcante AJW, Lopes SS, Saporito WF, Fucci FJC, Simon-Campos JA, Wang L, Liu LN, Wang QY, Wei D, Zhang Z, Chen ZN, Zhu P. Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial. Signal Transduct Target Ther. 2023 Jan 30;8(1):46. doi: 10.1038/s41392-023-01323-9.
PubMed 36717539Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PubMed 34473343
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Seamless, Randomized, Third-Party-Blind, Clinical Trial to Evaluate the Safety and Efficacy of Meplazumab in Addition to Standard of Care for the Treatment of COVID-19 in Hospitalized Adults
- ClinicalTrials.gov ID
- NCT04586153
- Acronym / sponsor ID
- MPZ-II-02
- Conditions
- COVID-19
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 174 participants (actual)
- Lead sponsor
- Jiangsu Pacific Meinuoke Bio Pharmaceutical Co LtdIndustry (pharma, biotech, devices)
- Study start
- 15 Feb 2021 (actual)
- Primary completion
- 2 Dec 2022 (actual)
- Study completion
- 18 Dec 2022 (actual)
- First posted
- 14 Oct 2020 (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 phase2/3 study will be conducted to evaluate the safety and efficacy of Meplazumab in addition to Standard of Care for the treatment of Corona Virus Disease(COVID) 19 in hospitalized adults
Detailed description
- Rationale: Meplazumab is a humanized anti-CD147 immunoglobulin 2 (IgG2) monoclonal antibody which is expected to block the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein to the human host-cell-expressed CD147, thereby blocking entry of SARS-CoV-2 into human tissue. This expectation is based on in vitro functional studies using Vero E6 cells infected with SARS-CoV-2 that demonstrated effective meplazumab mediated virus gene copy number inhibition upwards of 90% as evaluated by quantitative polymerase chain reaction. Meplazumab may also inhibit COVID-19 associated cytokine storm syndrome based on inhibition of the pro inflammatory factor Cyclophilin A host-cell CD147 interaction.
- Overall Design: This is a multicenter, seamless, randomized, third-party-blind, study to evaluate the safety and efficacy of meplazumab for the treatment of COVID 19 in hospitalized adults (≥18 years). Neither the subject nor the investigator shall be aware of the study drug identity, as the study drug is dispensed by a third party (eg, a pharmacist or nurse). Enrollment of subjects will be stopped once the total number of planned subjects have completed the Stage 1 Day 29 visit procedures. Once the interim analysis of Stage 1 study data is complete and the Independent Data Monitoring Committee (IDMC) has recommended the meplazumab dose that is safe and effective to carry forward into Stage 2, the study will resume subject enrollment. A summary of the key Stage 1 interim analysis results will be sent to the relevant Health Authorities involved, if requested.
- Number of Investigators and Study Centers: There will be 15 to 20 Investigators, at 12 to 20 study centers globally, participating in this study.
- Number of Subjects: Subjects will be screened 1 day before randomization. Stage 1: Approximately 168 subjects will be randomized and allocated 1:1:1:1 (42:42:42:42) to receive meplazumab low dose, meplazumab medium dose, meplazumab high dose, or control. An interim analysis will be conducted to select the optimal dose of meplazumab compared with the control group based on response rates of clinical improvement at Day 29. Stage 2: 276 more subjects will be randomized and allocated 1:1 (138:138) to receive 0.2mg/kg meplazumab or control. At interim analysis, primary endpoint, sample size calculation for Stage 2 will be re evaluated based on the observed outcomes at Stage 1 and will be capped at 300 subjects total.
- Treatment Groups and Duration:
Study duration for each subject will be 84±7 days from randomization in each stage.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Meplzaumb | Experimental | Drug: Meplazumab for InjectionThis arm is combined with 3 groups, low dose, middle dose, and high dose. Low dose group: First dose: 0.12 mg/kg - Day 1; second dose: control - Day 8 Middle dose group: First dose: 0.2 mg/kg - Day 1; second dose: 0.2 mg/kg - Day 8 High dose group: First dose: 0.3 mg/kg - Day 1; second dose: 0.3 mg/kg - Day 8 |
| Placebo | Placebo comparator | Drug: Sterile normal saline (0.9%)First dose: control - Day 1; second dose: control - Day 8 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adults (≥18 years) with laboratory-confirmed SARS CoV 2 infection as determined by PCR or other commercial or public health assay, which is FDA cleared or approved for emergency use (test results must be obtained within 72 hours of Day
- A score of Grade 3 (hospitalized, requiring supplemental oxygen) or Grade 4 (hospitalized, on non-invasive ventilation or high flow oxygen devices) on the 6-point ordinal scale.
- Willingness and ability to comply with study-related procedures and assessments.
- Ability to provide informed consent signed by study subject or legally authorized representative.
- Male and/or female
Key exclusion criteria (15 listed)
- Any physical examination findings, laboratory abnormality, and/or history of any illness, that in the study Investigator's judgment, could jeopardize the safety of the subject by their participation in the study.
- Subjects with evidence of critical COVID 19 illness, defined by at least 1 of the following: respiratory failure; shock (defined by systolic blood pressure <90 mm Hg, or diastolic blood pressure <60 mm Hg, or requiring vasopressors); or multi-organ dysfunction/failure.
- Subjects requiring extracorporeal membrane oxygenation (ECMO).
- Stage 4 severe chronic kidney disease or requiring dialysis (ie, estimated glomerular filtration rate(eGFR) mL/min/1.73 m2 < 30).
- Pregnant or breast feeding.
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 |
|---|---|---|
| Meplazumab for Injectionhumanized antibody target CD147 | Drug | Meplzaumb |
| Sterile normal saline (0.9%)Sterile normal saline (0.9%) | Drug | Placebo |
Primary outcome
Mortality (based on the interim analysis of Stage 1 data)
Time frame: During the evaluation period (Day 1 to Day 29)
Mortality (based on the interim analysis of Stage 1 data)
Proportion of subjects alive and discharged without supplemental oxygen
Time frame: During the evaluation period (Day 1 to Day 29)
To evaluate live discharge
3 secondary outcomes
Changes from baseline in cytokine, chemokines and related inflammatory factors.
Time frame: During the evaluation period (Day 1 to Day 29)
Viral load
Time frame: During the evaluation period (Day 1 to Day 29)
Viral negative rate of SARS-Cov-2 nucleic acid
Time frame: During the evaluation period (Day 1 to Day 29)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2023.
- Derived from this study: PubMed 36717539Bian H, Chen L, Zheng ZH, Sun XX, Geng JJ, Chen R, Wang K, Yang X, Chen SR, Chen SY, Xie RH, Zhang K, Miao JL, Jia JF, Tang H, Liu SS, Shi HW, Yang Y, Chen XC, Malhotra V, Nasir N, Khanum I, Mahmood F, Hamid S, Stadnik CMB, Itinose K, de Oliveira CCC, Dusilek C, Rivabem L, Cavalcante AJW, Lopes SS, Saporito WF, Fucci FJC, Simon-Campos JA, Wang L, Liu LN, Wang QY, Wei D, Zhang Z, Chen ZN, Zhu P. Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial. Signal Transduct Target Ther. 2023 Jan 30;8(1):46. doi: 10.1038/s41392-023-01323-9.
- Derived from this study: PubMed 34473343Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Meplazumab for Injection and Sterile normal saline (0.9%) in people with COVID-19, run by Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd at 1 site in Brazil.
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 10 inclusion and 15 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: finished, as of the sponsor's last update on 15 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Mortality (based on the interim analysis of Stage 1 data) (time frame: During the evaluation period (Day 1 to Day 29)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04586153, which also lists 2 linked publications.
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 15 Sep 2023.