Phase 2 Study of CAL02 plus Standard of Care in Severe Community-Acquired Bacterial Pneumonia (SCABP)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eagle Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

26 Sep 2023 → ongoing

Decision date (initial)

2023-10-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Eagle Pharmaceuticals, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy

- To evaluate the effect of CAL02 administration on clinical recovery compared to placebo
- To evaluate the safety and tolerability of CAL02 versus placebo

Secondary objectives 4

1. To evaluate the effect of CAL02 administration on the duration of critical care management compared to placebo
2. To evaluate the effect of CAL02 administration on the duration of overall hospital stay compared to placebo
3. To evaluate the effect of CAL02 administration on early clinical recovery (by Day 5) compared to placebo
4. To evaluate the effects of CAL02 administration on SOFA scores compared to placebo

Conditions and MedDRA coding

SEVERE COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA (SCABP)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Males or females ≥18 years old
2. Body weight 40 to 140 kg (88 to 308 lb), inclusive
3. Clinical diagnosis of CABP (diagnosed ≤48 hours after hospital admission)
4. Presence of at least one of the following severity criteria, based on protocol defined SCABP: a. Respiratory failure requiring invasive mechanical ventilation support b. Respiratory failure requiring non-invasive positive pressure ventilation support (eg, continuous positive airway pressure [C-PAP], bi-level positive airway pressure [Bi-PAP]) and partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) ≤250 mm Hg, excluding home setting non-invasive positive pressure ventilation support c. Respiratory failure requiring high-flow oxygen defined as >40 L/min and PaO2/FiO2 ratio ≤250 mm Hg d. Septic shock requiring treatment with vasopressors at therapeutic doses (defined as >0.07 μg/kg/min norepinephrine equivalent [Appendix 2]) for at least 2 hours to maintain or attempt to maintain mean arterial pressure ≥65 mm Hg after adequate fluid resuscitation
5. Onset of severity criteria <48 hours from diagnosis of CABP or upon discussion with medical monitor
6. Requires critical care for management of SCABP
7. Written informed consent obtained from subject or legally acceptable representative, as per the local guidelines, before any study-specific assessment is performed; assessments performed as standard of care may be accepted for study purposes

Exclusion criteria 14

1. Subjects with ventilator-associated pneumonia, aspiration pneumonia, hospital-acquired pneumonia, healthcare-associated pneumonia (HCAP), suspected or confirmed fungal pneumonia, or viral pneumonia (viral coinfection may be exempted subject to medical monitor discussion) (HCAP definition: hospitalization for 2 days or more within the preceding 90 days, residence in a nursing home or extended care facility, the use of home infusion therapy [including antibiotics], receipt of chronic dialysis within 30 days, home wound care and a history of infection with a multidrug-resistant pathogen in a family member)
2. More than 12 hours from the diagnosis of SCABP
3. SOFA score >12 points and cumulative points from central nervous system + liver function+coagulation ≥4 points at diagnosis of SCABP
4. Subject received IV antibiotics for CABP/SCABP for >48 hours at the time of randomization if sensitivity supports appropriate empiric therapy chosen and administered
5. Severe renal impairment as determined by estimated serum creatinine clearance of <30 mL/min according to the Cockcroft-Gault equation renal replacement therapy (eg, hemofiltration, hemodialysis, cytokine filters, etc.), or extracorporeal membrane oxygenation (ECMO) at the time of screening or the first IMP infusion
6. Known hypersensitivity to egg, egg components, or to liposomal formulations
7. End-stage neuromuscular disorders, tracheostomy, known bronchial obstruction (except for chronic obstructive pulmonary disease, asthma, emphysema, and non-cystic fibrosis bronchiectasis), post-obstructive aspiration pneumonia, cystic fibrosis, known or suspected Pneumocystis jirovecii or tuberculosis pneumonia, post organ transplant, or primary or metastatic malignancy in the lungs
8. Current or recent participation in an investigational study (within 30 days of screening, or 5 half-lives of the investigational compound, whichever is longer)
9. Known liver dysfunction, chronic liver disease with Child Pugh C or esophageal varices
10. Moribund clinical conditions at the time of screening or time of the first IMP infusion
11. Refractory septic shock at the time of the randomization, as defined by the inability to maintain mean arterial pressure ≥65 mm Hg despite IV fluids and use of any of the following: • Any vasopressor at >0.4 μg/kg/min norepinephrine equivalent (Appendix 2) (Jentzer 2018) or • 2 vasopressors at >0.1 μg/kg/min norepinephrine equivalent (Appendix 2) or • >2 vasopressors at any dose
12. Subject has any medical disease (acute, subacute, intermittent, or chronic) or condition (eg, severely immune compromised) that, in the opinion of the investigator, compromises the subject’s safety or compromises the interpretation of the results
13. Nursing and pregnant women (defined as the state after conception until the termination of gestation, screened in all women of childbearing potential with a urine dipstick test and, if positive, confirmed by a human chorionic gonadotropin [hCG] blood test)
14. Women of childbearing potential and non-surgically sterile male subjects who are sexually active and not willing to use an effective contraception from the time of consent until 30 days after the last dose of IMP unless local regulations require otherwise. Postmenopausal women are allowed to participate

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Time (days) to clinical recovery, the day all severity criteria which met the SCABP definition per protocol at randomization, and any new severity criteria which occurred after randomization, are resolved, and no repeat or additional severity criteria are met within 24 hours after recovery
2. Incidence and severity of TEAEs including infusion-related reactions
3. Incidence of IMP IV infusion interruptions and discontinuations

Secondary endpoints 4

1. Time to critical care management discharge (days)
2. Time to hospital discharge (days)
3. Proportion of subjects who achieve clinical recovery by Day 5
4. Relative change from baseline in whole SOFA score at Day 7

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eagle Pharmaceuticals Inc.

Sponsor organisation

Eagle Pharmaceuticals Inc.

Address

50 Tice Boulevard Suite 315

City

Woodcliff Lake

Postcode

07677-7637

Country

United States

Scientific contact point

Organisation

Eagle Pharmaceuticals Inc.

Contact name

Head of Clinical Drug Development

Public contact point

Organisation

Eagle Pharmaceuticals Inc.

Contact name

Head of Clinical Drug Development

Third parties 9

Locations

9 EU/EEA countries · 49 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

Temporary halts 9 · Art. 38 CTR

Results and documents

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

Documents 28 files

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

Application history

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