Sars-CoV-2Phase 2NCT04334460
Safety and Antiviral Activity of BLD-2660 in COVID-19 Hospitalized Subjects
A Phase 2 study testing BLD-2660 in people with Sars-CoV-2 and Covid19, run by Blade Therapeutics at 35 sites in 2 countries.
Trial summary
BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9 that is selective over the cathepsins as well as other protease families, displays good metabolic stability and permeability, oral bioavailability and low cytochrome P450 (CYP) inhibition. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sars-CoV-2, Covid19
- What is being tested?
- BLD-2660
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 35 sitesin 2 countries
- Study dates
- 4 May 2020to 21 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- At least 18 years of age at the time of signing the ICF.
- Hospitalized for COVID-19.
- Diagnosed with COVID-19 as defined by having at least 2 of the following signs or symptoms within the past 2 days:
- Fever defined as a body temperature of ≥ 38.0 °C oral, or ≥ 38.3 °C rectal, ≥37.7 °C forehead or ≥38.7°C aural (axillary temperatures are not allowable);
- Cough;
- Fatigue;
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- Shortness of breath.
- Radiographic evidence (chest x-ray or CT scan) of one the following:
- Ground-glass opacities, or
- Local or bilateral patchy infiltrates, or
- Interstitial pulmonary infiltrates.
- Oxygen requirements:
- SpO2 ≤ 94% on ambient air OR
- Requires supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
- Male and/or female subjects.
- Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- All subjects (male or female) who are of childbearing potential must agree to use highly effective contraception during the study. Female subjects and male partners of female subjects must continue to use highly effective contraception for 30 days after the last dose of study drug. Female subjects should not donate oocytes during this time. Male subjects and female partners of male subjects must continue to use highly effective contraception for 90 days. Male subjects must agree not to donate sperm during this time.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Note: Ethinyl estradiol is the primary estrogen used in hormonal contraceptives. The progestin component consists of norethindrone, levonorgestrel, norgestrel, norethindrone acetate, ethynodiol diacetate, norgestimate, desogestrel, and drospirenone. As BLD-2660 is a weak CYP3A4 inducer, exposure to both the estrogen and progestin components in hormonal contraceptives may be decreased, resulting in an increased risk of pregnancy. As such, it is recommended that subjects who are on hormonal contraceptives for birth control should use an alternate means of contraception (condoms, diaphragms, intrauterine device (IUD), other barrier methods, sexual abstinence, etc.) during participation in the study.
- Women of childbearing potential must have a negative serum pregnancy test at Screening within 72 hours prior to first administration of study drug.
- Women not of childbearing potential must be postmenopausal (defined as cessation of regular menstrual periods for at least 1 year
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
Who cannot join
- Active bacterial pneumonia infection
- Known active tuberculosis (TB).
- History of Child-Pugh B or C cirrhosis.
- History of ischemic heart disease or myocardial infarction or acute coronary syndrome.
- Subjects requiring supplemental oxygen ≥0.75 FiO2.
- It is not in the best interest of the subjects to participate, in the opinion of the treating Investigator.
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- Female subjects who are pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 90 days after the last dose of study drug.
- The following laboratory parameters are excluded:
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 x upper limit of normal (ULN);
- Creatinine clearance < 50 mL/min.
- Requiring, or expected to require mechanical ventilation at screening.
- Treatment with chloroquine or hydroxychloroquine at study entry.
- Treatment with anti-IL 6, anti-IL-6 receptor antagonists, or with Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period.
- Participation in any other clinical study of an experimental drug treatment for COVID-19 within 6 half-lives of the experimental treatment.
- Note: Subjects participating in an observational study are an exception to this criterion and may qualify for the study with Sponsor approval.
- Note: Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Unable to swallow solid oral medication or known malabsorption disorder.
- Subjects who have allergy to BLD-2660 or inactive components of BLD-2660.
Trial locations and contacts
35 sites in 2 countries.
35 sites in 2 countries
United States27 sites
Blade Research Site
Ames, Iowa, 50010
Blade Research Site
Baltimore, Maryland, 21201
Blade Research Site
Brandon, Florida, 33511
Blade Research Site
Charleston, North Carolina, 29414
Blade Research Site
Charleston, South Carolina, 29414
Blade Research Site
Dallas, Texas, 75203
Blade Research Site
Detroit, Michigan, 48202
Blade Research Site
Durham, North Carolina, 27708
Blade Research Site
Farmington Hills, Michigan, 48334
Blade Research Site
Fayetteville, North Carolina, 28304
Blade Research Site
Ft. Pierce, Florida, 34982
Blade Research Site
Idaho Falls, Idaho, 83404
Blade Research Site
Irvine, California, 92697
Blade Research Site
Lexington, Kentucky, 40503
Blade Research Site
Los Angeles, California, 90048
Blade Research Site
Louisville, Kentucky, 40207
Vanderbilt University Medical Center
Nashville, Tennessee, 37203
Blade Research Site
Omaha, Nebraska, 68114
Blade Research Site
Panama City, Florida, 32405
Blade Research Site
Peoria, Illinois, 61603
Blade Research Site
Philadelphia, Pennsylvania, 19140
Blade Research Site
Ridgewood, New Jersey, 07450
Blade Reseach Site
San Jose, California, 95128
Blade Research Site
Spokane, Washington, 99204
Blade Research Site
Tampa, Florida, 33620
Blade Research Site
Washington D.C., District of Columbia, 20007
Blade Research Site
Washington D.C., District of Columbia, 20010
Brazil8 sites
Blade Research Site
Bahia, 41810
Blade Research Site
Belo Horizonte, 30150
Blade Research Site
Botucatu, 18618
Blade Research Site
Campinas, São Paulo, 13034
Blade Research Site
Porto Velho, 76801
Blade Research Site
Ribeirão Preto, 65470
Blade Research Site
São José do Rio Preto, 15090
Blade Research Site
Vitória, 29041
About this study
Official title: Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Antiviral Activity of BLD-2660 in Hospitalized Subjects With Recently Diagnosed COVID-19 Compared to Standard of Care Treatment
BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9 that is selective over the cathepsins as well as other protease families, displays good metabolic stability and permeability, oral bioavailability and low cytochrome P450 (CYP) inhibition. It is under development for the treatment of coronavirus disease-19 (COVID-19) resulting from infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV2), where there is significant unmet medical need.
Read the detailed description
Interleukin 6 (IL-6), a proinflammatory cytokine, is a key driver of a cytokine storm that plays a significant role in clinical complications and acute lung injury. Emerging data indicate that serum levels of IL-6 are elevated in COVID-19 patients and are predictive of respiratory failure and mortality. IL-6 has been shown to contribute to lung damage during SARS-CoV infection and the virus itself is capable of directly inducing its expression. Suppression of pro-inflammatory IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections.
In a mouse model of lung injury employing bleomycin, BLD-2660, at therapeutic doses of 30 and 100 mg/kg twice per day (BID), reduced IL-6 levels in bronchoalveolar lavage (BAL) fluid. BLD-2660 also attenuated fibrosis damage as measured by significant reductions in the alpha smooth muscle actin and collagen 1 in lung tissue. BLD-2660 also demonstrated target engagement by inhibiting cleavage of one of its substrates, spectrin, in bronchoalveolar cells.
BLD-2660 was also evaluated in a mouse model of NASH fibrosis, demonstrating an anti-fibrotic effect. A significant decrease in IL-6 transcription was also observed. This suggests that the effect of BLD-2660 on IL-6 is independent of the injury, or the affected organ.
It has been shown that the receptor for SARS-CoV-1 and -2 entry into the cell is angiotensin-converting enzyme 2 (ACE-2). ACE-2 and the dimeric calpains (data on file) are co-expressed in respiratory epithelial cells, the site of both viral entry and predominant early lung injury in COVID-19. Inhibition of dimeric calpain activity has not been associated with impairment of normal immune function. The safety and tolerability of BLD-2660 has been demonstrated in the recently completed Phase 1 single ascending dose (SAD)/multiple ascending dose (MAD) B-2660-101 study.
As BLD-2660 has been demonstrated to (1) reduce tissue IL-6 levels and (2) attenuate lung fibrosis damage, it could therefore, potentially reduce the nonproductive IL-6 mediated host-response to infection, which contribute to morbidity and mortality in COVID-19. In addition, data suggest that survivors of SARS-CoV-2 infection are at risk for chronic impairment of pulmonary function, likely attributable to pulmonary fibrosis secondary to lung injury and inflammation. Although there is not yet available data documenting numbers of patients infected with SARS CoV2 pneumonia who progress to pulmonary fibrosis, epidemiology, viral immunology, and current clinical evidence support that pulmonary fibrosis may become one of the serious long-term complications of survivors of COVID-19 related pneumonia.
Thus, BLD-2660 could not only potentially downregulate the nonproductive host-response to infection, which contributes to morbidity and mortality in COVID-19 but also could reduce potential long-term fibrosis and loss of pulmonary function resulting from SARS-CoV pneumonia. This study will evaluate BLD-2660 as an add-on therapy to standard of care (SOC) in hospitalized subjects with recent diagnosis of COVID-19.
- Conditions
- Sars-CoV-2, Covid19
- Being tested
- BLD-2660
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BLD-2660Drug
BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.
| Study group | Role | What they receive |
|---|---|---|
| Active (BLD-2660) Group | Active comparator | Not described Receives: Drug: BLD-2660 |
| Placebo Group | Placebo comparator | Not described Receives: Drug: BLD-2660 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Recovery
To evaluate time to recovery as defined by no longer requiring oxygen support or hospital discharge, whichever occurs first.
Measured: Course of study; 28 days
Change in Oxygenation
To evaluate change in oxygenation in hospitalized adults with COVID-19 treated with BLD-2660. Measured by change from baseline to Day 10 or hospital discharge, if sooner, in the ratio of peripheral hemoglobin oxygen saturation to fraction of inspired oxygen (SpO2/FiO2)
Measured: 10 days
Secondary outcomes (1)
Safety & Tolerability: Incidence of TEAEs and Serious Adverse Events (SAEs)
To evaluate the safety and tolerability of BLD-2660 in the same population. Measured by incidence of TEAEs and serious adverse events (SAEs)
Measured: Course of study; 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2020
- Study start4 May 2020
- Primary completion11 Nov 2020
- Study completion21 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sars-CoV-2Studies 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Blade Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Clinipace Worldwide
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04334460
- Sponsor's protocol ID
- B-2660-204
- Status last verified
- Feb 2022
- First submitted
- 2 Apr 2020
- Last updated
- 6 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Antiviral Activity of BLD-2660 in Hospitalized Subjects With Recently Diagnosed COVID-19 Compared to Standard of Care Treatment
- ClinicalTrials.gov ID
- NCT04334460
- Acronym / sponsor ID
- B-2660-204
- Conditions
- Sars-CoV-2, Covid19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Blade TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Clinipace Worldwide
- Study start
- 4 May 2020 (actual)
- Primary completion
- 11 Nov 2020 (actual)
- Study completion
- 21 Jun 2021 (actual)
- First posted
- 6 Apr 2020 (actual)
- Results
- Posted 6 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9 that is selective over the cathepsins as well as other protease families, displays good metabolic stability and permeability, oral bioavailability and low cytochrome P450 (CYP) inhibition. It is under development for the treatment of coronavirus disease-19 (COVID-19) resulting from infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV2), where there is significant unmet medical need.
Detailed description
Interleukin 6 (IL-6), a proinflammatory cytokine, is a key driver of a cytokine storm that plays a significant role in clinical complications and acute lung injury. Emerging data indicate that serum levels of IL-6 are elevated in COVID-19 patients and are predictive of respiratory failure and mortality. IL-6 has been shown to contribute to lung damage during SARS-CoV infection and the virus itself is capable of directly inducing its expression. Suppression of pro-inflammatory IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections.
In a mouse model of lung injury employing bleomycin, BLD-2660, at therapeutic doses of 30 and 100 mg/kg twice per day (BID), reduced IL-6 levels in bronchoalveolar lavage (BAL) fluid. BLD-2660 also attenuated fibrosis damage as measured by significant reductions in the alpha smooth muscle actin and collagen 1 in lung tissue. BLD-2660 also demonstrated target engagement by inhibiting cleavage of one of its substrates, spectrin, in bronchoalveolar cells.
BLD-2660 was also evaluated in a mouse model of NASH fibrosis, demonstrating an anti-fibrotic effect. A significant decrease in IL-6 transcription was also observed. This suggests that the effect of BLD-2660 on IL-6 is independent of the injury, or the affected organ.
It has been shown that the receptor for SARS-CoV-1 and -2 entry into the cell is angiotensin-converting enzyme 2 (ACE-2). ACE-2 and the dimeric calpains (data on file) are co-expressed in respiratory epithelial cells, the site of both viral entry and predominant early lung injury in COVID-19. Inhibition of dimeric calpain activity has not been associated with impairment of normal immune function. The safety and tolerability of BLD-2660 has been demonstrated in the recently completed Phase 1 single ascending dose (SAD)/multiple ascending dose (MAD) B-2660-101 study.
As BLD-2660 has been demonstrated to (1) reduce tissue IL-6 levels and (2) attenuate lung fibrosis damage, it could therefore, potentially reduce the nonproductive IL-6 mediated host-response to infection, which contribute to morbidity and mortality in COVID-19. In addition, data suggest that survivors of SARS-CoV-2 infection are at risk for chronic impairment of pulmonary function, likely attributable to pulmonary fibrosis secondary to lung injury and inflammation. Although there is not yet available data documenting numbers of patients infected with SARS CoV2 pneumonia who progress to pulmonary fibrosis, epidemiology, viral immunology, and current clinical evidence support that pulmonary fibrosis may become one of the serious long-term complications of survivors of COVID-19 related pneumonia.
Thus, BLD-2660 could not only potentially downregulate the nonproductive host-response to infection, which contributes to morbidity and mortality in COVID-19 but also could reduce potential long-term fibrosis and loss of pulmonary function resulting from SARS-CoV pneumonia. This study will evaluate BLD-2660 as an add-on therapy to standard of care (SOC) in hospitalized subjects with recent diagnosis of COVID-19.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active (BLD-2660) Group | Active comparator | Drug: BLD-2660 |
| Placebo Group | Placebo comparator | Drug: BLD-2660 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- At least 18 years of age at the time of signing the ICF.
- Hospitalized for COVID-19.
- Diagnosed with COVID-19 as defined by having at least 2 of the following signs or symptoms within the past 2 days:
- Fever defined as a body temperature of ≥ 38.0 °C oral, or ≥ 38.3 °C rectal, ≥37.7 °C forehead or ≥38.7°C aural (axillary temperatures are not allowable);
- Cough;
Key exclusion criteria (18 listed)
- Active bacterial pneumonia infection
- Known active tuberculosis (TB).
- History of Child-Pugh B or C cirrhosis.
- History of ischemic heart disease or myocardial infarction or acute coronary syndrome.
- Subjects requiring supplemental oxygen ≥0.75 FiO2.
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 |
|---|---|---|
| BLD-2660BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9. | Drug | Active (BLD-2660) Group, Placebo Group |
Primary outcome
Time to Recovery
Time frame: Course of study; 28 days
To evaluate time to recovery as defined by no longer requiring oxygen support or hospital discharge, whichever occurs first.
Change in Oxygenation
Time frame: 10 days
To evaluate change in oxygenation in hospitalized adults with COVID-19 treated with BLD-2660. Measured by change from baseline to Day 10 or hospital discharge, if sooner, in the ratio of peripheral hemoglobin oxygen saturation to fraction of inspired oxygen (SpO2/FiO2)
1 secondary outcome
Safety & Tolerability: Incidence of TEAEs and Serious Adverse Events (SAEs)
Time frame: Course of study; 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
35 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BLD-2660 in people with Sars-CoV-2 and Covid19, run by Blade Therapeutics at 35 sites in 2 countries.
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 22 inclusion and 18 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 6 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, 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 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?
Yes. Results are posted in the registry (first posted 6 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to Recovery (time frame: Course of study; 28 days). 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?
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 6 Apr 2022.