Study Drug vs Placebo as an “add on” treatment for Severe Community-Acquired Pneumonia.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aptarion Biotech AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

4 Mar 2024 → 16 Mar 2026

Decision date (initial)

2024-02-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Aptarion Biotech AG

External identifiers

EU CT number

2023-505985-28-01

WHO UTN

U1111-1293-3210

ClinicalTrials.gov

NCT05962606

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Pharmacodynamic

To assess the safety and tolerability of AON-D21 in patients with severe CAP admitted to Intensive Care Unit (or similar unit).

Secondary objectives 3

1. To explore the efficacy of AON-D21 in patients with severe CAP admitted to Intensive Care Unit (or similar unit)
2. To characterise the pharmacokinetics of AON D21
3. To characterise the pharmacodynamics of AON-D21

Conditions and MedDRA coding

Severe Community-Acquired Pneumonia

Study design 1 period

Regulatory references

Plan to share IPD

No

IPD plan description

A description of this research study will be available on a publicly accessible website: https://clinicaltrials.gov or https://euclinicaltrials.eu/search-for-clinical-trials. Patients/LARs are advised in the PIS-ICF that they can search the websites at any time using the study number (S-D21-C300). Patients/LARs are advised in the PIS-ICF that the websites will include a summary of the results within 1 year after the end of the trial. Websites or publications will not include information that can identify them.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. At Screening, Randomisation and prior to administration of first dose; community-acquired pneumonia according to local guidelines. Community-acquired pneumonia may be confirmed or suspected to be of bacterial or viral origin.
2. At Screening, Randomisation and prior to administration of first dose; admitted to an Intensive Care Unit (or similar unit) defined as any hospital facility with intensive and specialised medical and nursing care, with capacity for monitoring, and physiological organ support to sustain life during a period of life-threatening organ system insufficiency.
3. At Screening, Randomisation and prior to administration of first dose: requiring respiratory support by High-Flow Oxygen ≥ 30 L/min with FiO2 ≥ 30% or Non-Invasive Mechanical Ventilation or Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation.
4. At Screening, C-reactive protein ≥ 50 mg/L. C-reactive protein measurement must be repeated and confirmed to be ≥ 50 mg/L if randomisation is not done within 24 h of Screening sample collection (local laboratory testing).
5. PaO2/FiO2 ratio ≤ 150 mmHg (≤ 20 kPa), with PaO2 from arterial blood (or arterialised capillary blood from a vasodilated ear lobe).
6. Treatment initiation no more than 48 h after initiation of respiratory support (High-Flow Oxygen ≥ 30 L/min with FiO2 ≥ 30%, Non-Invasive Mechanical Ventilation, Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation).
7. Written informed consent obtained from patient or legally designated representative or authorisation from an independent physician*, as per local guidelines. * In emergency situations, when prior consent of the participant or their legally designated representative is not possible, enrolment of the participant may be authorised by an independent physician (NON-EU Countries) or a treating physician independent of the research team (EU Countries), as per local guidelines. The participant or the participant’s legally designated representative should be informed about the trial as soon as possible, and consent should be requested.
8. Age ≥ 18 years to ≤ 85 years.
9. Body mass index ≥ 17.5 kg/m² and ≤ 40 kg/m².
10. For female participants of childbearing potential, agreement to use dual methods of contraception until Day 60.
11. For male participants with female partners of childbearing potential, agreement to use barrier method of contraception until Day 60 and to refrain from donating sperm during the study and for 3 months after the last infusion.

Exclusion criteria 18

1. Refractory septic shock at Screening, Randomisation or prior to administration of the first dose of study drug. Participants can be enrolled if they are no longer refractory. The presence of refractory septic shock shall be determined by the investigator. As a guidance, septic shock may be judged as refractory if treatment with ≥ 0.5 mcg/kg/min norepinephrine or equivalent (cumulative) for at least 2 h to maintain or attempt to maintain systolic blood pressure (SBP) >90 mmHg (or mean arterial pressure (MAP) >70 mmHg) after adequate fluid resuscitation is required.
2. Receiving chronic immunosuppressive therapy in clinically relevant doses (> 15 mg/day prednisolone or equivalent as maintenance treatment for > 14 days).
3. Known immunodeficiency disease/condition (iatrogenic or congenital), including human immunodeficiency virus infection (type 1 or 2) with CD4+ counts < 200 cells/µL, asplenia, or recurrent severe infections.
4. Nursing and pregnant women (defined as the state after conception until the termination of gestation, screened in all women of child-bearing potential with a chorionic gonadotrophin blood test (local laboratory).
5. Current or recent participation in an investigational trial (within 30 days of screening, or 5 half-lives of the respective investigational compound, whichever is longer).
6. Systemic treatment with any complement inhibitor, e.g., eculizumab or avacopan.
7. Known complement deficiency.
8. Known or suspected hypersensitivity to AON-D21 or any components of the formulation used (e.g., Polyethylene Glycol, mannitol or Ethylenediaminetetraacetic Acid) or a history of clinically relevant allergy requiring continuous treatment, or of anaphylaxis.
9. Unlikely to remain at the investigational site beyond 96 hours.
10. Not expected to survive 72 h, at Screening, Randomisation or prior to administration of first dose.
11. Hospital-acquired or ventilator-associated pneumonia or known or suspected pneumonia due to aspiration or other physical injury or trauma or tuberculosis.
12. Known fibrotic lung disease, bronchiectasis with ≥ 3 exacerbations requiring antibiotic treatment during the last year or any other known severe chronic respiratory disease (e.g., chronic obstructive pulmonary disease or cystic fibrosis) requiring home oxygen/non-invasive ventilation or with known forced expiratory volume in the first second < 30% of predicted.
13. Factors other than a pathogen suspected or confirmed to be causative for the respiratory insufficiency, e.g., clinically suspected pulmonary thromboembolism, cardiac insufficiency, including decompensated heart failure (≥ Class 3, New York Heart Association classification).
14. Active malignant disease with chemotherapy or immunomodulating cancer therapy within 30 days of screening or intended within the next 30 days or active primary lung cancer or another malignancy metastatic to the lungs or end-stage cancer.
15. Hepatocellular injury defined by an alanine aminotransferase or aspartate aminotransferase value ≥ 3 times the upper limit of normal (local laboratory). Known acute or chronic liver disease with Child-Pugh C.
16. Any medical disease (acute, subacute, intermittent, or chronic) or condition that, in the opinion of the investigator(s), compromises the participant’s safety or compromises the interpretation of the results.
17. Vasopressors, intubation, renal replacement therapy or cardiopulmonary resuscitation procedures are precluded on the basis of a patient order, next-of-kin communication or per staff decision. Clarification: The exclusion only applies when the precluded therapies or procedures result in a limitation in Standard of Care treatment escalation.
18. Applicable in France only. Persons under court protection, persons not affiliated to a social security system, protected adults (Art. L. 1121-6, Art. L. 1121-8, Art. L. 1121-8-1).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency, severity, and relatedness to study drug of serious and non-serious treatment-emergent adverse events until Day 28.

Secondary endpoints 10

1. Time to no longer requiring respiratory support (defined as High Flow Oxygen ≥ 30 L/min with FiO2 ≥ 30%, Non-Invasive Mechanical Ventilation, Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation) within 28 days.
2. Time to no longer requiring any organ support within 28 days.
3. Time to improvement (defined as a de-escalation in respiratory support; no oxygen support/other lower degree oxygen support < High Flow Oxygen ≥ 30 L/min with FiO2 ≥ 30% < Non-Invasive Mechanical Ventilation < Invasive Mechanical Ventilation < Extracorporeal Membrane Oxygenation) within 28 days.
4. Mean change in S/F ratio from Day 1 (Baseline) to Day 7.
5. Organ support-free days until Day 28.
6. Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation free days until Day 28.
7. Respiratory support-free days until Day 28.
8. All-cause mortality up to Days 28 and 60.
9. Area under the concentration-time curve (AUC) over the dosing interval at steady state (AUC0-tau), maximum concentration at steady state (Cmax), average drug concentration at steady state (Cav), trough concentrations (Ctrough), time of maximum concentration at steady state (tmax), terminal half-life at steady state (t1/2), accumulation ratios for Cmax and AUC, clearance (CL) and volume of distribution (Vz) of AON-D21 in plasma. From a subset of ≥ 20 participants from selected sites.
10. Determination of C5a inhibitory activity. From a subset of ≥ 100 participants.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aptarion Biotech AG

Sponsor organisation

Aptarion Biotech AG

Address

Max-Dohrn-Strasse 8-10, Charlottenburg Charlottenburg

City

Berlin

Postcode

10589

Country

Germany

Scientific contact point

Organisation

Aptarion Biotech AG

Contact name

Functional contact point

Public contact point

Organisation

Aptarion Biotech AG

Contact name

Functional contact point

Third parties 9

Locations

4 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications