Safety and Antiviral Activity of BLD-2660 in COVID-19 Hospitalized Subjects
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 |
---|---|---|
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
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
- 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.
- 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
- 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
- Time to Discharge Readiness [Course of study; 28 days]
Measured by time to discharge readiness
- 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.
- 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
- 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
- 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
- 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.
- 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
- 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
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)
More Information
Publications
None provided.- B-2660-204
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
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
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
|
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)
|
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%
|
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
|
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 |
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 |
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 |
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%
|
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%
|
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)
|
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. | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
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
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.
Results Point of Contact
Name/Title | SVP, Global Regulatory Affairs, Quality, and Safety |
---|---|
Organization | Blade Therapeutics |
Phone | (650) 278 4291 |
dmody@blademed.com |
- B-2660-204