Safety and Antiviral Activity of BLD-2660 in COVID-19 Hospitalized Subjects

• Sponsor: Blade Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04334460
• Collaborator: Clinipace Worldwide (Industry)
• Enrollment: 120
• Locations: 35
• Arms: 2
• Actual Duration (Months): 13.6
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Sars-CoV-2; Covid19	Drug: BLD-2660	Phase 2

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

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 4, 2020
• Actual Primary Completion Date: Nov 11, 2020
• Actual Study Completion Date: Jun 21, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active (BLD-2660) Group	Drug: BLD-2660; BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.
Placebo Comparator: Placebo Group	Drug: BLD-2660; BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.

Outcome Measures

Primary Outcome Measures

1. Time to Recovery [Course of study; 28 days]

   To evaluate time to recovery as defined by no longer requiring oxygen support or hospital discharge, whichever occurs first.

2. Change in Oxygenation [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)

Secondary Outcome Measures

1. Safety & Tolerability: Incidence of TEAEs and Serious Adverse Events (SAEs) [Course of study; 28 days]

   To evaluate the safety and tolerability of BLD-2660 in the same population. Measured by incidence of TEAEs and serious adverse events (SAEs)

Other Outcome Measures

1. Time to Discharge Readiness [Course of study; 28 days]

   Measured by time to discharge readiness

2. Proportion of Subjects Discharged During Study [Course of study; 28 days]

   Measured by proportion of subjects ready to be discharged from the hospital during the 28-day study period following enrollment.

3. Time to Resolution of Fever [Course of study; 28 days]

   Measured by time to resolution of fever below entry criteria for 24 hours in subjects with fever at baseline

4. Duration of Remdesivir Use [Course of study; 28 days]

   Measured by duration (in days) of remdesivir use in subjects starting remdesivir within 24 hours of first dose of BLD-2660

5. Change in Clinical Status [Course of study; 28 days]

   Measured by change from baseline to Days 10, 14, 21 and 28 in clinical status outcome using a 6-point ordinal scale

6. Percentage of Subjects in Each Category of the 6-point Ordinal Scale [Course of study; 28 days]

   Measured by percentage of subjects reporting each 6-point ordinal scale of the clinical status outcome assessment.

7. Change in IL-6 [Course of study; 28 days]

   Measured by change from baseline to Days 10, 14, 21 and 28 in IL-6 in ng/mL measured by analytical assay

8. Change in D-dimer [Course of study; 28 days]

   Measured by change from baseline to Days 10, 14, 21 and 28 in D-dimer in ng/mL measured by analytical assay

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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;

• 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

Exclusion Criteria:

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.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Blade Research Site	Irvine	California	United States	92697
2	Blade Research Site	Los Angeles	California	United States	90048
3	Blade Reseach Site	San Jose	California	United States	95128
4	Blade Research Site	Washington	District of Columbia	United States	20007
5	Blade Research Site	Washington	District of Columbia	United States	20010
6	Blade Research Site	Brandon	Florida	United States	33511
7	Blade Research Site	Fort Pierce	Florida	United States	34982
8	Blade Research Site	Panama City	Florida	United States	32405
9	Blade Research Site	Tampa	Florida	United States	33620
10	Blade Research Site	Idaho Falls	Idaho	United States	83404
11	Blade Research Site	Peoria	Illinois	United States	61603
12	Blade Research Site	Ames	Iowa	United States	50010
13	Blade Research Site	Lexington	Kentucky	United States	40503
14	Blade Research Site	Louisville	Kentucky	United States	40207
15	Blade Research Site	Baltimore	Maryland	United States	21201
16	Blade Research Site	Detroit	Michigan	United States	48202
17	Blade Research Site	Farmington Hills	Michigan	United States	48334
18	Blade Research Site	Omaha	Nebraska	United States	68114
19	Blade Research Site	Ridgewood	New Jersey	United States	07450
20	Blade Research Site	Charleston	North Carolina	United States	29414
21	Blade Research Site	Durham	North Carolina	United States	27708
22	Blade Research Site	Fayetteville	North Carolina	United States	28304
23	Blade Research Site	Philadelphia	Pennsylvania	United States	19140
24	Blade Research Site	Charleston	South Carolina	United States	29414
25	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37203
26	Blade Research Site	Dallas	Texas	United States	75203
27	Blade Research Site	Spokane	Washington	United States	99204
28	Blade Research Site	Campinas	Sao Paulo	Brazil	13034
29	Blade Research Site	Bahia		Brazil	41810
30	Blade Research Site	Belo Horizonte		Brazil	30150
31	Blade Research Site	Botucatu		Brazil	18618
32	Blade Research Site	Porto Velho		Brazil	76801
33	Blade Research Site	Ribeirão Preto		Brazil	65470
34	Blade Research Site	São José Do Rio Preto		Brazil	15090
35	Blade Research Site	Vitória		Brazil	29041

Sponsors and Collaborators

• Blade Therapeutics
• Clinipace Worldwide

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 8, 2020
• Statistical Analysis Plan - Oct 22, 2020

More Information

Publications

None provided.

• Responsible Party: Blade Therapeutics
• ClinicalTrials.gov Identifier: NCT04334460
• Other Study ID Numbers: B-2660-204
• First Posted: Apr 6, 2020
• Last Update Posted: Apr 6, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Arm/Group Title	Active Group	Placebo Group
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.	Placebo: Placebo-to-Match BLD-2660
Period Title: Full Enrollment
STARTED	81	39
COMPLETED	81	39
NOT COMPLETED	0	0
Period Title: Full Enrollment
STARTED	81	39
COMPLETED	77	38
NOT COMPLETED	4	1
Period Title: Full Enrollment
STARTED	81	39
COMPLETED	77	38
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Active Group	Placebo Group	Total
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.	Placebo to Match (PTM) the active BLD-2660	Total of all reporting groups
Overall Participants	81	39	120
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.3 (12.97)	54.2 (13.95)	52.2 (13.31)
Sex: Female, Male (Count of Participants)
Female	42 51.9%	13 33.3%	55 45.8%
Male	39 48.1%	26 66.7%	65 54.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	45 55.6%	19 48.7%	64 53.3%
Not Hispanic or Latino	35 43.2%	19 48.7%	54 45%
Unknown or Not Reported	1 1.2%	1 2.6%	2 1.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 2.6%	1 0.8%
Native Hawaiian or Other Pacific Islander	1 1.2%	0 0%	1 0.8%
Black or African American	13 16%	11 28.2%	24 20%
White	60 74.1%	20 51.3%	80 66.7%
More than one race	7 8.6%	7 17.9%	14 11.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	40 49.4%	19 48.7%	59 49.2%
Brazil	41 50.6%	20 51.3%	61 50.8%
APACHE II Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.5 (5.41)	6.5 (4.84)	6.5 (5.22)
6-Point Ordinal Scale (Count of Participants)
1 - Not hospitalized	0 0%	0 0%	0 0%
2 - Hospitalized, not requiring supplemental oxygen	6 7.4%	1 2.6%	7 5.8%
3 - Hospitalized, requiring supplemental oxygen	60 74.1%	25 64.1%	85 70.8%
4 - Hospitalized, on non-invasive ventilation or high flow oxygen device	6 7.4%	7 17.9%	13 10.8%
5 - Hospitalized, on invasive mechanical ventilation or ECMO	0 0%	0 0%	0 0%
6 - Death	0 0%	0 0%	0 0%
7 - Missing	5 6.2%	5 12.8%	10 8.3%
SpO2/FiO2 Ratio (Ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Ratio]	299.2 (61.89)	290.8 (72.34)	296.3 (65.41)
SARS-Cov-2 PCR Viral Load (copies/mL) (copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [copies/mL]	5703533.3 (30719776.01)	553963.0 (2177374.66)	4036053.4 (25348615.41)
IL-6 (ng/mL) (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	12.9 (27.60)	11.3 (13.10)	12.4 (23.71)
D-Dimer (ug/mL) (ug/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ug/mL]	0.8 (0.70)	0.8 (0.62)	0.8 (0.67)

Outcome Measures

1. Primary Outcome

Title	Time to Recovery
Description	To evaluate time to recovery as defined by no longer requiring oxygen support or hospital discharge, whichever occurs first.
Time Frame	Course of study; 28 days

Outcome Measure Data

Analysis Population Description

FAS Set

Arm/Group Title	Active Group	Placebo Group
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.	Placebo: Placebo-to-Match BLD-2660
Measure Participants	77	38
Median (95% Confidence Interval) [days]	5	4.5

2. Primary Outcome

Title	Change in Oxygenation
Description	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)
Time Frame	10 days

Outcome Measure Data

Analysis Population Description

FAS Set

Arm/Group Title	Active Group	Placebo Group
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.	Placebo: Placebo-to-Match BLD-2660
Measure Participants	77	38
Least Squares Mean (Standard Error) [Ratio]	33.8 (17.10)	66.8 (25.58)

3. Secondary Outcome

Title	Safety & Tolerability: Incidence of TEAEs and Serious Adverse Events (SAEs)
Description	To evaluate the safety and tolerability of BLD-2660 in the same population. Measured by incidence of TEAEs and serious adverse events (SAEs)
Time Frame	Course of study; 28 days

Outcome Measure Data

Analysis Population Description

Safety Set

Arm/Group Title	Active Group	Placebo Group
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.	Placebo to Match (PTM) the active BLD-2660
Measure Participants	77	38
Number of Subjects with >=1 TEAE	42 51.9%	23 59%
Number of Subjects with >=1 Treatment-Related TEAE	10 12.3%	6 15.4%
Number of Subjects with >=1 TEAE with Grade 3 or higher	12 14.8%	9 23.1%
Number of Subjects with >=1 TE SAE	9 11.1%	9 23.1%
Number of Subjects with >=1 Treatment-Related SAE	0 0%	1 2.6%
Number of Subjects with >=1 TEAE leading to discontinuation of study drug	2 2.5%	5 12.8%
Number of fatal AEs	2 2.5%	2 5.1%

4. Other Pre-specified Outcome

Title	Time to Discharge Readiness
Description	Measured by time to discharge readiness
Time Frame	Course of study; 28 days

Outcome Measure Data

Analysis Population Description

FAS Set

Arm/Group Title	Active Group	Placebo Group
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.	Placebo to Match (PTM) the active BLD-2660
Measure Participants	77	38
Median (95% Confidence Interval) [Days]	7.0	8.0

5. Other Pre-specified Outcome

Title	Proportion of Subjects Discharged During Study
Description	Measured by proportion of subjects ready to be discharged from the hospital during the 28-day study period following enrollment.
Time Frame	Course of study; 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Time to Resolution of Fever
Description	Measured by time to resolution of fever below entry criteria for 24 hours in subjects with fever at baseline
Time Frame	Course of study; 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Duration of Remdesivir Use
Description	Measured by duration (in days) of remdesivir use in subjects starting remdesivir within 24 hours of first dose of BLD-2660
Time Frame	Course of study; 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Change in Clinical Status
Description	Measured by change from baseline to Days 10, 14, 21 and 28 in clinical status outcome using a 6-point ordinal scale
Time Frame	Course of study; 28 days

Outcome Measure Data

Analysis Population Description

FAS Set

Arm/Group Title	Active Group	Placebo Group
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.	Placebo to Match (PTM) the active BLD-2660
Measure Participants	77	38
1 - Not hospitalized	4 4.9%	0 0%
2 - Hospitalized, not requiring supplemental oxygen	44 54.3%	23 59%
3 - Hospitalized, requiring supplemental oxygen	20 24.7%	8 20.5%
4 - Hospitalized, on non-invasive ventilation or high flow oxygen device	3 3.7%	3 7.7%
5 - Hospitalized, on invasive mechanical ventilation or ECMO	5 6.2%	2 5.1%
6 - Death	0 0%	0 0%
7 - Missing	1 1.2%	2 5.1%
1 - Not hospitalized	56 69.1%	21 53.8%
2 - Hospitalized, not requiring supplemental oxygen	5 6.2%	2 5.1%
3 - Hospitalized, requiring supplemental oxygen	1 1.2%	1 2.6%
4 - Hospitalized, on non-invasive ventilation or high flow oxygen device	3 3.7%	1 2.6%
5 - Hospitalized, on invasive mechanical ventilation or ECMO	3 3.7%	2 5.1%
6 - Death	0 0%	0 0%
7 - Missing	9 11.1%	11 28.2%
1 - Not hospitalized	54 66.7%	20 51.3%
2 - Hospitalized, not requiring supplemental oxygen	2 2.5%	1 2.6%
3 - Hospitalized, requiring supplemental oxygen	1 1.2%	1 2.6%
4 - Hospitalized, on non-invasive ventilation or high flow oxygen device	0 0%	0 0%
5 - Hospitalized, on invasive mechanical ventilation or ECMO	3 3.7%	1 2.6%
6 - Death	0 0%	0 0%
7 - Missing	17 21%	15 38.5%
1 - Not hospitalized	63 77.8%	24 61.5%
2 - Hospitalized, not requiring supplemental oxygen	0 0%	1 2.6%
3 - Hospitalized, requiring supplemental oxygen	1 1.2%	0 0%
4 - Hospitalized, on non-invasive ventilation or high flow oxygen device	0 0%	0 0%
5 - Hospitalized, on invasive mechanical ventilation or ECMO	3 3.7%	1 2.6%
6 - Death	0 0%	0 0%
7 - Missing	10 12.3%	12 30.8%

9. Other Pre-specified Outcome

Title	Percentage of Subjects in Each Category of the 6-point Ordinal Scale
Description	Measured by percentage of subjects reporting each 6-point ordinal scale of the clinical status outcome assessment.
Time Frame	Course of study; 28 days

Outcome Measure Data

Analysis Population Description

FAS Set

Arm/Group Title	Active Group	Placebo Group
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.	Placebo to Match (PTM) the active BLD-2660
Measure Participants	77	38
Day 10 (EOT)	76 93.8%	36 92.3%
Day 14 (Follow-Up)	68 84%	27 69.2%
Day 21 (Follow-Up)	60 74.1%	23 59%
Day 28	67 82.7%	26 66.7%

10. Other Pre-specified Outcome

Title	Change in IL-6
Description	Measured by change from baseline to Days 10, 14, 21 and 28 in IL-6 in ng/mL measured by analytical assay
Time Frame	Course of study; 28 days

Outcome Measure Data

Analysis Population Description

FAS Set. Only participants in the FAS with data at the respective time point are summarized.

Arm/Group Title	Active Group	Placebo Group
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.	Placebo to Match (PTM) the active BLD-2660
Measure Participants	77	38
Day 10	5.606 (13.6212)	4.592 (8.8388)
Day 14	29.547 (196.4762)	25.892 (82.0965)
Day 21	3.361 (6.6323)	1.981 (1.9770)
Day 28	6.639 (28.6087)	2.649 (4.0756)

11. Other Pre-specified Outcome

Title	Change in D-dimer
Description	Measured by change from baseline to Days 10, 14, 21 and 28 in D-dimer in ng/mL measured by analytical assay
Time Frame	Course of study; 28 days

Outcome Measure Data

Analysis Population Description

FAS Set

Arm/Group Title	Active Group	Placebo Group
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.	Placebo to Match (PTM) the active BLD-2660
Measure Participants	77	38
Day 10	0.51	0.67
Day 14	0.54	0.57
Day 21	0.50	0.56
Day 28	0.57	0.41

Adverse Events

Time Frame	6 months.
Arm/Group Title	Active Group		Placebo Group
Arm/Group Description	BLD-2660: BLD-2660 is a novel, synthetic, orally active, small molecule inhibitor of calpain (CAPN) 1, 2, and 9.		Placebo to Match (PTM) the active BLD-2660
All Cause Mortality
	Active Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/77 (2.6%)		2/38 (5.3%)
Serious Adverse Events
	Active Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/77 (11.7%)		9/38 (23.7%)
Cardiac disorders
Bradycardia	1/77 (1.3%)		0/38 (0%)
Cardiac arrest	1/77 (1.3%)		0/38 (0%)
Atrioventricular block second degree	0/77 (0%)		1/38 (2.6%)
General disorders
Pyrexia	1/77 (1.3%)		0/38 (0%)
Infections and infestations
Acinetobacter bacteraemia	1/77 (1.3%)		0/38 (0%)
Pneumonia	1/77 (1.3%)		1/38 (2.6%)
Sepsis	1/77 (1.3%)		1/38 (2.6%)
Septic shock	1/77 (1.3%)		0/38 (0%)
Bacteraemia	0/77 (0%)		1/38 (2.6%)
COVID-19	0/77 (0%)		1/38 (2.6%)
Pneumonia bacterial	0/77 (0%)		1/38 (2.6%)
Investigations
Hepatic enzyme increased	0/77 (0%)		1/38 (2.6%)
Renal and urinary disorders
Acute kidney injury	1/77 (1.3%)		2/38 (5.3%)
Renal failure	1/77 (1.3%)		0/38 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	3/77 (3.9%)		1/38 (2.6%)
Acute respiratory distress syndrome	1/77 (1.3%)		0/38 (0%)
Pulmonary embolism	1/77 (1.3%)		0/38 (0%)
Acute respiratory failure	0/77 (0%)		1/38 (2.6%)
Hypoxia	0/77 (0%)		1/38 (2.6%)
Vascular disorders
Shock	1/77 (1.3%)		0/38 (0%)
Hypotension	0/77 (0%)		1/38 (2.6%)
Other (Not Including Serious) Adverse Events
	Active Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/77 (54.5%)		23/38 (60.5%)
Blood and lymphatic system disorders
Anaemia	1/77 (1.3%)		0/38 (0%)
Leukocytosis	1/77 (1.3%)		0/38 (0%)
Leukopenia	1/77 (1.3%)		0/38 (0%)
Cardiac disorders
Angina pectoris	1/77 (1.3%)		0/38 (0%)
Cardiomegaly	0/77 (0%)		1/38 (2.6%)
Ear and labyrinth disorders
Ear congestion	1/77 (1.3%)		0/38 (0%)
Eye disorders
Dry eye	1/77 (1.3%)		0/38 (0%)
Gastrointestinal disorders
Nausea	6/77 (7.8%)		7/38 (18.4%)
Diarrhoea	4/77 (5.2%)		1/38 (2.6%)
Abdominal pain upper	2/77 (2.6%)		0/38 (0%)
Change of bowel habit	1/77 (1.3%)		0/38 (0%)
Constipation	1/77 (1.3%)		1/38 (2.6%)
Dyspepsia	1/77 (1.3%)		1/38 (2.6%)
Flatulence	1/77 (1.3%)		0/38 (0%)
Gastrooesophageal reflux disease	1/77 (1.3%)		0/38 (0%)
Retching	1/77 (1.3%)		0/38 (0%)
Vomiting	1/77 (1.3%)		1/38 (2.6%)
Anal incontinence	0/77 (0%)		1/38 (2.6%)
Haematemesis	0/77 (0%)		1/38 (2.6%)
Upper gastrointestinal haemorrhage	0/77 (0%)		1/38 (2.6%)
General disorders
Fatigue	1/77 (1.3%)		0/38 (0%)
Generalised oedema	1/77 (1.3%)		0/38 (0%)
Non-cardiac chest pain	1/77 (1.3%)		1/38 (2.6%)
Vessel puncture site bruise	0/77 (0%)		1/38 (2.6%)
Immune system disorders
Drug hypersensitivity	0/77 (0%)		1/38 (2.6%)
Infections and infestations
Fungal infection	2/77 (2.6%)		0/38 (0%)
Upper respiratory tract infection	1/77 (1.3%)		1/38 (2.6%)
Urinary tract candidiasis	1/77 (1.3%)		0/38 (0%)
Sinusitis	0/77 (0%)		1/38 (2.6%)
Investigations
Alanine aminotransferase increased	4/77 (5.2%)		1/38 (2.6%)
Aspartate aminotransferase increased	4/77 (5.2%)		1/38 (2.6%)
Fibrin D dimer increased	2/77 (2.6%)		0/38 (0%)
Gamma-glutamyltransferase increased	2/77 (2.6%)		0/38 (0%)
Blood bicarbonate decreased	1/77 (1.3%)		0/38 (0%)
Blood creatinine increased	1/77 (1.3%)		0/38 (0%)
Blood glucose increased	1/77 (1.3%)		0/38 (0%)
Blood potassium decreased	1/77 (1.3%)		0/38 (0%)
Blood pressure increased	1/77 (1.3%)		0/38 (0%)
Breath sounds abnormal	1/77 (1.3%)		0/38 (0%)
Electrocardiogram QT prolonged	1/77 (1.3%)		1/38 (2.6%)
Transaminases increased	1/77 (1.3%)		0/38 (0%)
Troponin increased	0/77 (0%)		1/38 (2.6%)
Metabolism and nutrition disorders
Hypokalaemia	3/77 (3.9%)		0/38 (0%)
Hypophosphataemia	2/77 (2.6%)		0/38 (0%)
Hypervolaemia	1/77 (1.3%)		0/38 (0%)
Type 2 diabetes mellitus	0/77 (0%)		1/38 (2.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/77 (0%)		1/38 (2.6%)
Myalgia	0/77 (0%)		1/38 (2.6%)
Nervous system disorders
Dizziness	3/77 (3.9%)		3/38 (7.9%)
Migraine	1/77 (1.3%)		1/38 (2.6%)
Headache	0/77 (0%)		2/38 (5.3%)
Myasthenia gravis	0/77 (0%)		1/38 (2.6%)
Psychiatric disorders
Anxiety	2/77 (2.6%)		1/38 (2.6%)
Abnormal dreams	1/77 (1.3%)		0/38 (0%)
Agitation	1/77 (1.3%)		0/38 (0%)
Delirium	1/77 (1.3%)		0/38 (0%)
Depression	1/77 (1.3%)		0/38 (0%)
Hallucination, visual	1/77 (1.3%)		0/38 (0%)
Insomnia	1/77 (1.3%)		1/38 (2.6%)
Hallucination	0/77 (0%)		1/38 (2.6%)
Renal and urinary disorders
Urinary hesitation	1/77 (1.3%)		0/38 (0%)
Urinary incontinence	0/77 (0%)		1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/77 (2.6%)		1/38 (2.6%)
Pulmonary amyloidosis	1/77 (1.3%)		0/38 (0%)
Hiccups	0/77 (0%)		1/38 (2.6%)
Productive cough	0/77 (0%)		1/38 (2.6%)
Skin and subcutaneous tissue disorders
Pruritus	1/77 (1.3%)		0/38 (0%)
Rash	1/77 (1.3%)		0/38 (0%)
Subcutaneous emphysema	1/77 (1.3%)		0/38 (0%)
Hyperhidrosis	0/77 (0%)		1/38 (2.6%)
Vascular disorders
Hypertension	1/77 (1.3%)		1/38 (2.6%)
Orthostatic hypotension	1/77 (1.3%)		0/38 (0%)
Arterial occlusive disease	0/77 (0%)		1/38 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.