IFX-1-P2.9

InflaRx GmbH

Winzerlaer Strasse 2, Jena, Germany, 07745

Clinical Research and Development, InflaRX GmbH, +49 (0)3641-508 150, Niels.Riedemann@inflarx.de

Clinical Research and Development, InflaRX GmbH, +49 (0)3641-508 150, Niels.Riedemann@inflarx.de

No

No

No

Final

21 Mar 2022

Yes

31 Oct 2021

Yes

01 Dec 2021

No

The primary objective of Phase II was to explore the effect of vilobelimab on COVID-19 related severe pneumonia (hypothesis generating). The primary objective of Phase III was to demonstrate the efficacy of vilobelimab to improve survival outcomes of invasively mechanically ventilated COVID-19 pneumonia patients.

Phase II: An Independent Safety Monitoring Board (ISMB) was constituted to support safety surveillance in both treatment arms throughout the phase II part of the study. The committee included 2 intensive care specialists not involved as Investigator in this study and an independent statistician. The ISMB monitored the safety of all patients regularly, after 10, 20, and 30 patients had completed their treatment in part II. At each review, the ISMB was able to recommend on continuing or ending the study. All available safety data were provided to the ISMB before each meeting. After completion of Phase II (30 patients), the ISMB assessed the totality of available data of all patients and recommended on proceeding to Phase III. In Phase III, the ISMB from Phase II continued as an Independent (Clinical Trial) Data Monitoring Committee (IDMC). The IDMC met every 3 months throughout Phase III of the study to further assess safety. In addition, the IDMC performed an unblinded assessment of the data of the interim analysis and made recommendations on whether to continue the study or not according to the predefined early stop criterion. All available data were provided to the IDMC before each meeting. Details were described in a separate IDMC Charter.

31 Mar 2020

No

Yes

Netherlands: 169

Belgium: 15

France: 35

Germany: 21

Mexico: 37

Peru: 15

Brazil: 74

Russian Federation: 23

South Africa: 10

399

240

0

0

0

0

0

0

279

120

0

Overall trial (Phase II & III) (overall period)

Randomised - controlled

Phase II of the study was open-label and randomized, while Phase III was double-blind, placebo-controlled, and randomized.

Yes

IFX-1

IFX-1

vilobelimab

Injection/infusion

Intravenous use

Patients in the Phase II IFX-1 + BSC arm were to be treated with a maximum of 7 intravenous (IV) doses of IFX-1 800 mg over a period of 29 days. The first 5 treatments at Days 1, 2, 4, 8, and 15 were to be administered to all patients randomized into the IFX-1 + BSC arm. Treatment at Day 22 was only to be administered in the event that a patient had not been extubated and discharged from ICU. In case a patient’s clinical situation worsened after Day 8, although an initial clinical benefit was observed, one additional administration of 800 mg IFX-1 between Days 11 and 13 could have been given at Investigator’s discretion. IFX-1 was administered as a 30-min infusion (-5/+10 min).

Best supportive care

BSC

Not assigned

Not mentioned

BSC in the participating centers consisted of intensive care therapy according to current guidelines, evidence, and best practice, including but not limited to lung protective ventilation, thrombosis prophylaxis, renal replacement therapy, when indicated, and access to advanced therapies including extracorporeal membrane oxygenation. Use of antimalarials (e.g., chloroquine) was allowed during the study; however, active concomitant treatment with other immunomodulatory drugs was not allowed.

Best supportive care

BSC

Not assigned

Not mentioned

BSC in the participating centers consisted of intensive care therapy according to current guidelines, evidence, and best practice, including but not limited to lung protective ventilation, thrombosis prophylaxis, renal replacement therapy, when indicated, and access to advanced therapies including extracorporeal membrane oxygenation. Use of antimalarials (e.g., chloroquine) was allowed during the study; however, active concomitant treatment with other immunomodulatory drugs was not allowed.

IFX-1

IFX-1

vilobelimab

Injection/infusion

Intravenous use

Phase III: Patients were treated with a maximum of six intravenous (iv) doses of IFX-1 800 mg administered as a 30-60-minute iv infusion. The six treatments were at Days 1, 2, 4, 8, 15, and 22 as long as the patient was still hospitalized, even if discharged from ICU.

Standard of care

SOC

Not assigned

Not mentioned

All patients received SOC for the treatment of COVID-19, which included venous thromboembolism prophylaxis with anticoagulants at a minimum. Other international or country-specific recommended treatments for COVID-19 per the locally adopted treatment recommendations (including but not limited to corticosteroids, remdesivir, and other locally adopted SOC) were allowed as concomitant medications. SOC treatment was given at the Investigator’s discretion and could start and stop at any time.

Standard of care

SOC

Not assigned

Not mentioned

All patients received standard of care (SOC) for the treatment of COVID-19, which included venous thromboembolism prophylaxis with anticoagulants at a minimum. Other international or country-specific recommended treatments for COVID-19 per the locally adopted treatment recommendations (including but not limited to corticosteroids, remdesivir, and other locally adopted SOC) were allowed as concomitant medications. SOC treatment was given at the Investigator’s discretion and could start and stop at any time.

Placebo

Placebo

Infusion

Intravenous use

Patients received a maximum of six intravenous (iv) doses of Placebo administered as a 30-60-minute iv infusion. The six administrations were at Days 1, 2, 4, 8, 15, and 22 as long as the patient was still hospitalized, even if discharged from ICU.

Phase II: IFX-1 + BSC

Phase II: Best Supportive Care (BSC)

Phase III: IFX-1 + SOC

Phase III: Placebo + SOC

FAS (Phase II)

All randomized patients were included in the Full Analysis Set (FAS) according to the intention-to-treat principle, irrespective of their protocol adherence and continued participation in the study. Patients were analyzed according to their randomized treatment arm.

SAF (Phase III)

Safety analyses were based on all patients who received at least one infusion of IMP; patients were analyzed according to the treatment they actually received. The actual treatment group of each patient was VILO if they received any VILO infusion at any timepoint, and Placebo if they received only Placebo infusions at all timepoints.

FAS (Phase III)

The primary efficacy analyses was performed based on all randomized patients according to the intention-to-treat principle, except for patients who were randomized in error (reason for early termination documented as “Randomized by mistake” in the eCRF) and did not receive IMP.

Phase II: IFX-1 + BSC

Phase II: Best Supportive Care (BSC)

Phase III: IFX-1 + SOC

Phase III: Placebo + SOC

FAS (Phase II)

All randomized patients were included in the Full Analysis Set (FAS) according to the intention-to-treat principle, irrespective of their protocol adherence and continued participation in the study. Patients were analyzed according to their randomized treatment arm.

SAF (Phase III)

Safety analyses were based on all patients who received at least one infusion of IMP; patients were analyzed according to the treatment they actually received. The actual treatment group of each patient was VILO if they received any VILO infusion at any timepoint, and Placebo if they received only Placebo infusions at all timepoints.

FAS (Phase III)

The primary efficacy analyses was performed based on all randomized patients according to the intention-to-treat principle, except for patients who were randomized in error (reason for early termination documented as “Randomized by mistake” in the eCRF) and did not receive IMP.

The primary endpoint of the Phase II part of the study was the relative change (%) from baseline (Day 1 prior to study drug administration at ± 1h of randomization) in Oxygenation Index (PaO2 / FiO2) in supine position at Day 5. Reported is the least square (LS) mean (95% confidence interval) for the relative change from baseline per arm for the FAS from a linear repeated measures model adjusting for covariates baseline Oxygenation Index, time point, sex, age, and intubation status.

Primary

Baseline until Day 5

Phase II: Best Supportive Care (BSC) v Phase II: IFX-1 + BSC

29

Pre-specified

-16.4

2-sided

Standard error of the mean

17.91

The primary efficacy endpoint was 28-day all-cause mortality, i.e. the proportion of patients deceased until Day 28.

Primary

28 days

Cox proportional hazards regression model of 28-day all-cause mortality with explanatory variables treatment group and age as well as a stratification by site.

Phase III: Placebo + SOC v Phase III: IFX-1 + SOC

368

Pre-specified

0.728

2-sided

Standard error of the mean

0.18948

Cox proportional hazards regression model of 28-day all-cause mortality with explanatory variables treatment group and age without stratification by site.

Phase III: IFX-1 + SOC v Phase III: Placebo + SOC

368

Pre-specified

0.674

2-sided

Age-adjusted Cox regression with random effect for site (“frailty” model).

Phase III: Placebo + SOC v Phase III: IFX-1 + SOC

368

Post-hoc

0.648

2-sided

Phase III: Placebo + SOC v Phase III: IFX-1 + SOC

368

Post-hoc

0.613

2-sided

Logistic regression: Missing values were imputed by multiple imputation. This analysis was performed on the all randomized patient set including the one patient who was randomized in error and excluded from the FAS. For this analyses the number of subjects analyzed is 369.

Phase III: IFX-1 + SOC v Phase III: Placebo + SOC

368

Pre-specified

-11

2-sided

Phase III: IFX-1 + SOC v Phase III: Placebo + SOC

368

Post-hoc

All AEs, serious and non-serious, were to be collected, documented, and reported from signing the informed consent onwards until the EOT visit / 30 days following the last IFX-1 administration.

Adverse events for Phase II, Arm IFX-1 + BSC and Arm BSC, are reported for FAS. Adverse events for Phase III, Arm IFX-1 + SOC and Arm Placebo + SOC, are reported for SAF.

23.0

IFX-1 + BSC

Best Supportive Care (BSC)

IFX-1 + SOC

Placebo + SOC