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Severe COVID-19 PneumoniaPhase 2/3PANAMONCT04333420

Randomized, Controlled Study of IFX-1 in Patients With Severe COVID-19 Pneumonia

A Phase 2/3 study testing IFX-1 + BSC, BSC and IFX-1 + SOC in people with Severe COVID-19 Pneumonia, run by InflaRx GmbH at 48 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Phase II \& Phase III: This is a pragmatic, adaptive, randomized, multicenter phase II/III study evaluating IFX-1 for the treatment of COVID-19 related severe pneumonia. The study consists of two parts: Phase II, an open-label, randomized, 2-arm phase evaluating best supportive care (BSC) + IFX-1 (Arm A) and BSC alone… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Severe COVID-19 Pneumonia
What is being tested?
IFX-1 + BSC, BSC and IFX-1 + SOC
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
399 participants
Where
48 sitesin 9 countries
Study dates
31 Mar 2020to 1 Dec 2021
Phase
Phase 2/3
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 or older
  • Clinically evident or otherwise confirmed severe pneumonia
  • SARS-CoV-2 infection confirmation (tested positive in last 14 days before randomization with locally available test system)
  • At least 18 years of age or older
  • Patient on invasive mechanical ventilation (but not more than 48h post intubation at time point of first IMP administration)
  • Patients with a PaO2 / FiO2 ratio of < 200 and > 60 at randomization (one representative measurement within 6h before randomization)
  • SARS-CoV-2 infection confirmation (tested positive in last 14 days before randomization with locally available test system)

Who cannot join

  • Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months
  • Patient moribund or expected to die in next 24h according to the judgment of the investigator
  • Known severe congestive heart failure (New York Heart Association [NYHA] Class III- IV)
  • Received organ or bone marrow transplantation in past 3 months
  • Known cardio-pulmonary mechanical resuscitation in past 14 days
  • Phase III:
Show all 15Show fewer
  • Intubated > 48 h at time point of first IMP administration
  • Expected stop of invasive ventilation or expected extubation in the next 24h without additional intervention according to judgment of the investigator
  • Known history of chronic dialysis OR received renal replacement therapy in past 14 days OR anticipated to receive renal replacement therapy within 24h after randomization
  • Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months
  • Treatment of COVID-19 with investigational antibody treatment(s) which are not approved or not included in locally adopted treatment guidelines (e.g., WHO guidance, National Institutes of Health [NIH] COVID-19 treatment guidelines) for this indication in the past 7 days (Note: Antibody treatment[s] given within past 7 days for pre-existing diseases, other than COVID-19, are allowed.)
  • At time point of randomization, treatment of COVID-19 with investigational treatments which are not approved or not included in locally adopted treatment guidelines for this indication (e.g., WHO guidance, NIH COVID-19 treatment guidelines), including SARS-CoV-2 multiplication inhibitor(s) or immunomodulator(s). (Note: If a locally adopted treatment guideline recommends drugs such as remdesivir, dexamethasone, or anticoagulation, this would be allowed. Adopted guidelines and updates must be documented at study initiation and throughout the conduct of the study.)
  • Received cytokine adsorption therapy in past 3 days
  • Known severe congestive heart failure (corresponding to e.g. NYHA Class III-IV, left ventricular ejection fraction <40%)
  • Known history of chronic liver disease (Child-Pugh B or C)

Trial locations and contacts

48 sites in 9 countries.

48 sites in 9 countries

France10 sites

  • InflaRx Site #1011

    Grenoble

  • InflaRx Site #1005

    Nantes

  • InflaRx Site #1009

    Nantes

  • InflaRx Site #1003

    Nice

  • InflaRx Site #1001

    Paris

  • InflaRx Site #1004

    Paris

  • InflaRx Site #1006

    Paris

  • InflaRx Site #1008

    Paris

  • InflaRx Site #1012

    Saint-Etienne

  • InflaRx Site #1002

    Suresnes

Other trials in France

Germany8 sites

  • InflaRx Site #0201

    Aachen

  • InflaRx Site #0207

    Augsburg

  • InflaRx Site #0202

    Berlin

  • InflaRx Site #0208

    Dresden

  • InflaRx Site #0204

    Essen

  • InflaRx Site #0203

    Greifswald

  • InflaRx Site #0205

    Hanover

  • InflaRx Site #0206

    Jena

Other trials in Germany

Brazil7 sites

  • InflaRx Site #0301

    Belo Horizonte

  • InflaRx Site #0302

    Campinas

  • InflaRx Site #0305

    Criciúma

  • InflaRx Site #0308

    Curitiba

  • InflaRx Site #0304

    Porto Alegre

  • InflaRx Site #0303

    São José

  • InflaRx Site #0306

    São Paulo

Other trials in Brazil

Mexico6 sites

  • InflaRx Site #0502

    Chihuahua City

  • InflaRx Site #0503

    Culiacán

  • InflaRx Site #0506

    Mérida

  • InflaRx Site #0504

    Monterrey

  • InflaRx Site #0501

    Nuevo León

  • InflaRx Site #0505

    Veracruz

Other trials in Mexico

Belgium5 sites

  • InflaRx Site #1107

    Aalst

  • InflaRx Site #1102

    Brussels

  • InflaRx Site #1104

    Leuven

  • InflaRx Site #1106

    Lodelinsart

  • InflaRx Site #1101

    Yvoir

Other trials in Belgium

Netherlands5 sites

  • InflaRx Site #0101

    Amsterdam

  • InflaRx Site #0103

    Amsterdam

  • InflaRx Site #0106

    Eindhoven

  • InflaRx Site #0104

    Enschede

  • InflaRx Site #0102

    Maastricht

Other trials in Netherlands

Peru3 sites

  • InflaRx Site #0601

    Callao

  • InflaRx Site #0603

    Lima

  • InflaRx Site #0604

    Lima

Other trials in Peru

Russia3 sites

  • InflaRx Site #0701

    Barnaul

  • InflaRx Site #0704

    Moscow

  • InflaRx Site #0702

    Ryazan

Other trials in Russia

South Africa1 site

  • InflaRx Site # 0804

    Somerset West

Other trials in South Africa

About this study

Official title: A Pragmatic Adaptive Randomized, Controlled Phase II/III Multicenter Study of IFX-1 in Patients With Severe COVID-19 Pneumonia

Phase II \& Phase III:

This is a pragmatic, adaptive, randomized, multicenter phase II/III study evaluating IFX-1 for the treatment of COVID-19 related severe pneumonia. The study consists of two parts: Phase II, an open-label, randomized, 2-arm phase evaluating best supportive care (BSC) + IFX-1 (Arm A) and BSC alone (Arm B); and Phase III, a double-blind, placebo-controlled, randomized phase comparing standard of care (SOC) + IFX-1 (Arm A) versus SOC + placebo-to-match (Arm B)

Read the detailed description

The phase II and Phase III portions enrolled patients subsequently.

1st patient was enrolled in the phase III portion on 1st October 2020.

Being tested
IFX-1 + BSC, BSC, IFX-1 + SOC, Placebo + SOC
Keywords
COVID-19 related severe pneumonia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IFX-1 + BSCDrug

    Also called Vilobelimab + Best Supportive Care

    Phase II study part: IFX-1 + BSC

  • BSCDrug

    Also called Best Supportive Care

    Phase II study part: BSC

  • IFX-1 + SOCDrug

    Also called Vilobelimab + Standard of Care

    Phase III study part: IFX-1 + SOC

  • Placebo + SOCDrug

    Also called Placebo + Standard of Care

    Phase III study part: Placebo + SOC

Study groups in NCT04333420
Study groupRoleWhat they receive
Phase II: IFX-1 + BSCExperimentalPhase II study part: IFX-1: 800mg intravenously administered, BSC: Best supportive care
Receives: Drug: IFX-1 + BSC
Phase II: BSCOtherPhase II study part: BSC: Best supportive care
Receives: Drug: BSC
Phase III: IFX-1 + SOCExperimentalPhase III study part: IFX-1: 800mg intravenously administered, SOC: Standard of care
Receives: Drug: IFX-1 + SOC
Phase III: Placebo + SOCPlacebo comparatorPhase III study part: Placebo: placebo infusion intravenously administered, SOC: Standard of care
Receives: Drug: Placebo + SOC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position at Day 5 (FAS)

    Relative change (%) from baseline in Oxygenation Index (OI; partial pressure of oxygen in the arterial blood (PaO2) / fractional inspired oxygen (FiO2)) in supine position for ≥2 hours at day 5 (FAS)

    Measured: Baseline and Day 5

  2. Phase III: 28-day All-cause Mortality (FAS)

    Number and percentage of deaths (all-cause) until Day 28 (FAS)

    Measured: Day 28

Secondary outcomes (8)

  1. Phase II: All-cause 28-day Mortality (FAS)

    Number and percentage of deaths (all-cause) until Day 28 (FAS)

    Measured: Day 28

  2. Phase II: Early Response at Day 7 After Enrollment

    Number of patients (%) achieving an early response at day 7 after enrollment (FAS)

    Measured: Day 7

  3. Phase II: Late Response Until Day 28 After Enrollment

    Number of patients (%) reaching a late response until day 28 (FAS)

    Measured: Baseline until Day 28

  4. Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position (FAS)

    Relative change (%) from baseline in Oxygenation Index (OI) in supine position for ≥2 hours at days 3, 7, 9, 11, and 15 (FAS)

    Measured: Baseline, Day 3, Day 7, Day 9, Day 11, Day 15

  5. Phase III: 60-day All-cause Mortality (FAS)

    Number and percentage of deaths (all-cause) until Day 60 (FAS)

    Measured: Day 60

  6. Phase III: Percentage of Patients With an Improvement in the 8-point Ordinal Scale (FAS)

    Percentage of patients with an improvement in the 8-point ordinal scale (Day 15, Day 28), the scale ranges from 0 = 'No clinical or virological evidence of infection' to 8 = 'Death' with higher scores meaning greater limitation and ventilation/organ support

    Measured: Day 15, Day 28

  7. Phase III: Percentage of Patients Developing Acute Kidney Failure Until Day 28 (FAS)

    Percentage of patients developing acute kidney failure (estimated glomerular filtration rate [eGFR] < 15 mL/min/1.73m², assessed by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation requiring race information) until Day 28 (FAS)

    Measured: Day 28

  8. Phase III: Percentage of Patients Free of Any Renal Replacement Therapy Within 28 Days Upon Randomization (FAS)

    Percentage of patients free of any renal replacement therapy (RRT) within 28 days upon randomization (FAS), number of patients free of any RRT = number of patients - number of patients with RRT initiated after randomization until Day 28

    Measured: Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Apr 2020
  2. Study start31 Mar 2020
  3. Primary completion31 Oct 2021
  4. Study completion1 Dec 2021

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Two phases with 2 parallel arms each
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
399 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04333420
Sponsor's protocol ID
IFX-1-P2.9
Other IDs
2020-001335-28
Acronym
PANAMO
Status last verified
Mar 2023
First submitted
1 Apr 2020
Last updated
5 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • van Amstel RBE, Slim MA, Lim EHT, Ruckinger S, Seymour CW, Burnett BP, Bos LDJ, van Vught LA, Riedemann NC, van de Beek D, Vlaar APJ; PANAMO Study Group. Heterogeneity of treatment effect of vilobelimab in COVID-19: a secondary analysis of a randomised controlled trial. Crit Care. 2024 Jun 28;28(1):210. doi: 10.1186/s13054-024-05004-z.

    PubMed 38943192

  • Lim EHT, Vlaar APJ, de Bruin S, Ruckinger S, Thielert C, Habel M, Guo R, Burnett BP, Dickinson J, Brouwer MC, Riedemann NC, van de Beek D; PANAMO study group. Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients. Intensive Care Med Exp. 2023 Jun 19;11(1):37. doi: 10.1186/s40635-023-00520-8.

    PubMed 37332066

  • Vlaar APJ, Witzenrath M, van Paassen P, Heunks LMA, Mourvillier B, de Bruin S, Lim EHT, Brouwer MC, Tuinman PR, Saraiva JFK, Marx G, Lobo SM, Boldo R, Simon-Campos JA, Cornet AD, Grebenyuk A, Engelbrecht JM, Mukansi M, Jorens PG, Zerbib R, Ruckinger S, Pilz K, Guo R, van de Beek D, Riedemann NC; PANAMO study group. Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022 Dec;10(12):1137-1146. doi: 10.1016/S2213-2600(22)00297-1. Epub 2022 Sep 7.

    PubMed 36087611

  • Vlaar APJ, Lim EHT, de Bruin S, Ruckinger S, Pilz K, Brouwer MC, Guo RF, Heunks LMA, Busch MH, van Paassen P, Riedemann NC, van de Beek D. The anti-C5a antibody vilobelimab efficiently inhibits C5a in patients with severe COVID-19. Clin Transl Sci. 2022 Apr;15(4):854-858. doi: 10.1111/cts.13213. Epub 2022 Jan 14.

    PubMed 35029045

  • Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

    PubMed 34473343

  • Vlaar APJ, de Bruin S, Busch M, Timmermans SAMEG, van Zeggeren IE, Koning R, Ter Horst L, Bulle EB, van Baarle FEHP, van de Poll MCG, Kemper EM, van der Horst ICC, Schultz MJ, Horn J, Paulus F, Bos LD, Wiersinga WJ, Witzenrath M, Rueckinger S, Pilz K, Brouwer MC, Guo RF, Heunks L, van Paassen P, Riedemann NC, van de Beek D. Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial. Lancet Rheumatol. 2020 Dec;2(12):e764-e773. doi: 10.1016/S2665-9913(20)30341-6. Epub 2020 Sep 28.

    PubMed 33015643

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing IFX-1 + BSC, BSC and IFX-1 + SOC in people with Severe COVID-19 Pneumonia, run by InflaRx GmbH at 48 sites in 9 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 7 inclusion and 15 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 5 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in France, Germany, Brazil, Mexico, Belgium and 4 more countries. 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 5 Jun 2023). 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?

Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position at Day 5 (FAS) (time frame: Baseline and Day 5). 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?

On the ClinicalTrials.gov record for NCT04333420, which also lists 6 linked publications.

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 5 Jun 2023.

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