A recent open-label study in patients with pulmonary sequelae subsequent to COVID-19 infection indicated that Longidaza^® was associated with improvements in pulmonary function, exercise tolerance, and respiratory symptoms⁷.

We conducted the “Long-CoV-III” randomized, double-blind, placebo-controlled clinical trial to further evaluate the possible effects of Longidaza^® on COVID-19 pulmonary sequelae.

Long-CoV-III was a randomized, double-blind, placebo-controlled trial in patients with a history of COVID-19, residual lung abnormalities, restrictive pulmonary disease, dyspnea, and decreased oxygen saturation at rest or after exercise. The study was conducted at 37 sites. A total of 392 patients were randomized 1:1 to receive intramuscular injections of Longidaza^® (3000 IU) or placebo every 5 days for 71 days. After completion of treatment, patients entered a 109-day follow-up. The efficacy was assessed in the full analysis set of 376 patients who successfully completed the study.

In total, 392 patients were randomized and dosed with Longidaza^® or placebo; 382 completed the trial. All randomized patients were included in the safety analysis, while the Full Analysis Set (FAS) comprised 376 patients (186 Longidaza^®, 190 placebo). Patients were excluded from the FAS primarily due to non-compliance with restrictive pulmonary disease criteria (FVC<80%, FEV1/FVC>70%).

Primary endpoint:

• Change from baseline in Forced Vital Capacity (percent of predicted, ppFVC) by Day 71

Secondary endpoints related to pulmonary function:

• Change from baseline in ppFVC by Day 180
• The proportion of patients who achieved at least 10% ppFVC increase by days 71 and 180.

Secondary endpoint related to exercise tolerance and respiratory symptoms:

• The proportion of patients exhibiting exertional desaturation (defined as a ≥4% decrease in SpO2 after 6-minute walk test (6-MWT)) on days 71 and 180
• The proportion of patients with exertional dyspnea (defined by a ≥2 point increase on the Borg scale after 6-MWT) on days 71 and 180
• The proportion of patients achieving a ≥50 meter increase in distance walked during the 6-MWT compared to the distance at baseline on days 71 and 180
• The proportion of patients with a decrease in resting dyspnea from baseline by ≥1 point on the mMRC scale on days 71 and 180

For exploratory subgroup analysis, patients were stratified by COVID-19 start date (before February 14, 2022, vs. on or after February 14, 2022); by age (≤60 years vs. >60 years); by sex; by the presence of cardiovascular comorbidities defined by MedDRA system organ classes.

In the overall population Longidaza^® had no significant effect on ppFVC growth. However, it was associated with faster ppFVC recovery in patients with cardiovascular comorbidities (n=281, diff=-3.31%, p=0.042) and those with an earlier COVID-19 infection (n=188, diff=-4.17%, p=0.021).

Longidaza^® showed a trend towards an increase in the proportion of patients achieving ≥10% ppFVC growth. On Day 180, 68% of patients in the Longidaza^® group and 58.4% of patients in the placebo group exhibited at least a 10% ppFVC increase from baseline (OR=1.51 ; p=0.058). Longidaza^® was also linked to a significantly higher proportion of patients in specific subgroups (age >60, female, and with cardiovascular comorbidities) achieving a 10% increase in ppFVC by Day 180.

Longidaza^® was associated with a significant decrease in the proportion of patients experiencing desaturation and dyspnea after a six-minute walk test (6-MWT) at days 71 and 180.

Longidaza^® was associated with a significant decrease in resting dyspnea and a trend towards the increased distance walked in six-minute test by Day 180.

Seventy-three (37%) of 196 patients in the Longidaza^® group and 49 (25%) of 196 patients in the placebo group experienced adverse events during the study. Eight adverse events in seven patients were deemed related to Longidaza^®. These included three injection site reactions, and single cases of elevated alanine aminotransferase levels, elevated C-reactive protein, thrombocytopenia, hives, and angina pectoris. One participant receiving placebo experienced a case of thrombocytopenia that was considered related to treatment. Three patients in the Longidaza^® group had serious adverse events, though these were not related to Longidaza^®. Adverse events led to the discontinuation of the study drug in five patients receiving Longidaza^® and one patient in the placebo group.

Full study results link