A Phase 1b/2a Study of the Safety and Pharmacokinetics of Rhu-plasma Gelsolin in Hospitalized Subjects With CAP

NCT03466073 | Completed Phase 1 Results DMC

• 1 other identifier: BTI-201
• Study Type: interventional
• Target: 33
• Locations: 2 countries
• Sites: 8

Brief Summary

A Phase 1b/2a, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Plasma gelsolin (rhu-pGSN) Added to Standard of Care in Subjects Hospitalized for Acute Community-acquired Pneumonia (CAP)

Conditions

Community-acquired Pneumonia

Keywords

Recombinant human plasma gelsolin (rhu-pGSN); Severe community-acquired pneumonia (sCAP); Adjunctive therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Treatment emergent adverse events were all adverse events (AEs) that occurred subsequent to enrollment. The seriousness of adverse events was judged by the site investigator.

  0-28 days

Secondary Outcomes (2)

• Pharmacokinetics (PK) (Area Under the Rhu-pGSN Concentration - Time Curve)

  On Days 0-3, specimens were obtained just prior and immediately post dose and 2, 8,12 and/or 16 , and 24 hours post completion of IV administration. In the single-dose arm, only 1 dose was given and thus no data from later days were obtained.

• Pharmacokinetics (PK) (Maximum Observed Rhu-pGSN Plasma Concentration (Cmax))

  On Days 0-3, specimens were obtained just prior and immediately post dose and 2, 8, 12 and/or 16, and 24 hours post completion of IV administration. In the single-dose arm, only 1 dose was given and thus no data from later days were obtained.

Other Outcomes (2)

• Number of Participants With Anti-pGSN Antibodies (Immunogenicity) at the End of Study (Day 28)

  Day 28

• Baseline and Sequential Severity Scores

  Days 0-28

Study Arms (4)

Single Dose 6 mg/kg

EXPERIMENTAL

Intravenous administration of recombinant human plasma gelsolin at 6 mg/kg v. placebo (NSS) in addition to standard of care

Drug: Recombinant Human Plasma Gelsolin; Other: Normal Saline Placebo

Multiple Dose 6 mg/kg

EXPERIMENTAL

Intravenous administration of recombinant human plasma gelsolin at 6 mg/kg once per day for 3 days v. placebo (NSS) in addition to standard of care

Drug: Recombinant Human Plasma Gelsolin; Other: Normal Saline Placebo

Multiple Dose 12 mg/kg

EXPERIMENTAL

Intravenous administration of recombinant human plasma gelsolin at 12 mg/kg once per day for 3 days v. placebo (NSS) in addition to standard of care

Drug: Recombinant Human Plasma Gelsolin; Other: Normal Saline Placebo

Multiple Dose 24 mg/kg

EXPERIMENTAL

Intravenous administration of recombinant human plasma gelsolin at 24 mg/kg once per day for 3 days v. placebo (NSS) in addition to standard of care

Drug: Recombinant Human Plasma Gelsolin; Other: Normal Saline Placebo

Interventions

Recombinant Human Plasma Gelsolin DRUG

Recombinant human plasma gelsolin lyophilized for reconstitution, reconstituted in sterile water

Also known as: rhu-pGSN

Multiple Dose 12 mg/kg; Multiple Dose 24 mg/kg; Multiple Dose 6 mg/kg; Single Dose 6 mg/kg

Normal Saline Placebo OTHER

Normal saline in volume equivalent to drug

Also known as: NSS (0.9% normal saline)

Multiple Dose 12 mg/kg; Multiple Dose 24 mg/kg; Multiple Dose 6 mg/kg; Single Dose 6 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent obtained from subject
• Domicile: home, assisted living, rehabilitation facility, or nursing home (as long as the prospective participant is capable of providing written informed consent)
• Duration of infection precipitating hospitalization by history \<14 days
• Planned or actual admission to hospital with a primary diagnosis of CAP within 24 hours of presentation to the hospital
• Primary admitting diagnosis of pneumonia supported by a compatible clinical presentation with a documented infiltrate consistent with pneumonia on chest radiograph or CT, as assessed by the admitting emergency-department (ED), clinic, or ward physician or equivalent caregiver
• Recommended (not mandatory) guidance/discretionary criteria defining patients with CAP:
• At least 2 symptoms: difficulty breathing, cough, production of purulent sputum, chest pain
• At least 2 vital sign abnormalities: fever, tachycardia, tachypnea
• At least one finding of other clinical signs and laboratory abnormalities: hypoxemia, clinical evidence of pulmonary consolidation, an elevated total white blood cell (WBC) count or leukopenia
• Chest imaging showing new (or presumed new or worsening) infiltrates
• Receipt of antibiotic treatment prior to presentation does not exclude the patient

You may not qualify if:

• Pregnant or lactating women
• Use of any investigational drug in the past 30 days
• Hospitalization during the last 30 days
• Residence within the last 30 days in long-term care facility where the patient remains persistently unable to participate in the routine activities of daily living
• Active underlying cancer treated with systemic chemotherapy or radiation therapy during the last 30 days
• Known or suspected immunosuppressive disease or therapy (including steroid use equivalent to prednisone ≥20 mg/day for \>7 days or known advanced human immunodeficiency virus (HIV) infection with CD4 count ≤200/mm3; specific testing for HIV status or CD4 count is not required but can be done at the discretion of the caregivers)
• Active congestive heart failure, myocardial infarction, or pulmonary embolism; cardiopulmonary arrest in last 30 days
• Weight \>100 kg
• Otherwise unsuitable for study participation in the opinion of the investigator

Sponsors & Collaborators

• BioAegis Therapeutics Inc.: lead

Study Sites (8)

Cairns Hospital

Cairns, Queensland, 4870, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Footscray Hospital

Footscray, Victoria, 3011, Australia

Location

LTD Geo Hospitals, Mtskheta Multiprofile Medical Center

Mtskheta, 3300, Georgia

Location

JSC Rustavi Central Hospital

Rustavi, 3700, Georgia

Location

LTD Central University Clinic After Academic N. Kipshidze

Tbilisi, 0160, Georgia

Location

LTD S. Khechinashvili University Hospital

Tbilisi, 0179, Georgia

Location

LTD 5th Clinical Hospital

Tbilisi, 0191, Georgia

Location

Related Publications (1)

• Tannous A, Levinson SL, Bolognese J, Opal SM, DiNubile MJ. Safety and Pharmacokinetics of Recombinant Human Plasma Gelsolin in Patients Hospitalized for Nonsevere Community-Acquired Pneumonia. Antimicrob Agents Chemother. 2020 Sep 21;64(10):e00579-20. doi: 10.1128/AAC.00579-20. Print 2020 Sep 21.

  PMID: 32690640 DERIVED

MeSH Terms

Conditions

Community-Acquired Pneumonia

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Mark DiNubile MD
• Organization: BioAegis Therapeutics Inc.

mdinubile@bioaegistx.com

609-706-5866

Study Officials

• Mark J DiNubile, MD

  BioAegis Therapeutics Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: visibly indistinguishable therapy
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential dose escalation

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: March 15, 2018
• Study Start: August 28, 2018
• Primary Completion: April 2, 2019
• Study Completion: April 2, 2019
• Last Updated: January 27, 2020
• Results First Posted: January 27, 2020

Record last verified: 2020-01

Locations

AU (3); GE (5)