SepsisPhase 1NCT01438853
Effects of TNX-832 (Sunol cH36) in Subjects With Acute Lung Injury/Acute Respiratory Distress Syndrome
A Phase 1 study testing TNX-832 in people with Sepsis and Acute Lung Injury, run by Altor BioScience at 7 sites in 2 countries.
Trial summary
This Phase I/IIa, multi-center, randomized, placebo-controlled, single-blinded dose-escalation study evaluated TNX-832 (also referred to as ALT-836 and Sunol cH36) in subjects with suspected or proven bacteria-induced ALI/ARDS. Up to five cohorts of at least six subjects each were originally planned. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Acute Lung Injury, Acute Respiratory Distress Syndrome
- What is being tested?
- TNX-832
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Dec 2004to Feb 2008
- Phase
- Phase 1
- 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
- ≥ 18 years
- Suspected or proven bacterial infection
- Receiving positive pressure ventilation through an endotracheal tube
- Have ALI/ARDS, defined as having all of the following:
- bilateral infiltrates consistent with pulmonary edema
- Hypoxemia
- no clinical evidence of left atrial hypertension
- Provide signed informed consent
Who cannot join
- Mechanically or chemically-induced ALI/ARDS (including burns, trauma, and near drowning)
- End-stage lung disease
- Decompensated congestive heart failure
- Authorization to withdraw life support
- Hemoglobin persistently <8.0 g/dL
- Subjects who have any one of the following:
Show all 48Show fewer
- platelet count <50,000/mm^3
- prolonged prothrombin time (PT)
- prolonged activated partial thromboplastin time (aPTT)
- having significant potential for disseminated intravascular coagulation (DIC)
- Subjects who have two or more of the following:
- prolonged aPTT
- fibrinogen level below the lower limit of normal
- presence of petechiae, ecchymoses, or other evidence of coagulopathy
- Subjects who have a history of one or more of the following:
- hematuria (microscopic or gross)
- urinary tract neoplasia
- nephrolithiasis
- glomerulonephritis
- active urinary tract infection (UTI)
- Bleeding disorders within the past 6 weeks or vasculitis with diffused alveolar hemorrhage
- Diagnosis of bleeding peptic ulcer disease within the previous 2 months
- Congenital bleeding diatheses such as hemophilia
- Treatment with anti-platelet, anti-coagulant agents, or non-steroidal anti-inflammatory drugs (NSAIDs)within 72 hours following infusion of study drug
- Therapeutic heparin:
- Unfractionated heparin within eight hours prior to study drug infusion
- Low molecular weight heparins within the 12 hours prior to study drug infusion
- Prophylactic heparin:
- Unfractionated heparin >15,000 units/day
- Low molecular weight heparins
- Warfarin if used within 7 days prior to study drug infusion
- Thrombolytic treatment within 3 days prior to study drug infusion
- 8Glycoprotein IIb/IIIa antagonists within 7 days prior to study drug infusion
- Aspirin or any aspirin containing compound within 3 days prior to study drug infusion
- APC infusion within 72 hours prior to study drug infusion
- Major trauma or trauma subjects at an increased risk of bleeding
- History of severe head trauma that required hospitalization, intracranial surgery, or stroke or any history of intracerebral arteriovenous malformation, cerebral aneurysm, or central nervous system mass lesion with an epidural catheter or who anticipate receiving an epidural catheter during study drug infusion
- Major surgery within the previous 3 days, any postoperative subject with evidence of active bleeding, or any subject with planned or anticipated surgery within 72 hours after study drug infusion. History of abnormal bleeding during surgical procedures
- Chronic renal failure, defined as a calculated glomerular filtration rate (GFR) ≤20 mL/min
- Subjects with baseline aspartate transaminase (AST) or alanine transaminase (ALT) level >5 times the upper limit of normal. Subjects with known esophageal varices, chronic jaundice, biopsy proven cirrhosis, or chronic ascites
- History of organ transplant (including bone marrow)
- Subjects with malignancy having a life expectancy <6 months
- Known human immunodeficiency virus (HIV) positive with CD4+ T Cell count <200/uL
- Women who are pregnant or nursing
- Participation in another clinical research study within 30 days before administration of study drug, with the exception of participation in studies involving noninvasive monitoring medical devices
- Any prior treatment with a murine or chimeric antibody
- Subjects who are moribund and where death is perceived to be imminent (within 72 hours after screening)
- Subjects who have persistent hypotension not responding to fluid or vasopressor administration; subjects who require more than two vasopressors 26. Any medical condition which in the opinion of the investigator would interfere with optimal participation in the study or that would produce a significant risk to a subject
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Akron General Medical Center
Akron, Ohio, 44307
Beth Israel Deconess Medical Center
Boston, Massachusetts, 02215
Baylor School of Medicine
Houston, Texas, 77030
University of Miami
Miami, Florida, 33125
Washington University
St Louis, Missouri, 63130
Wake Forest University
Winston-Salem, North Carolina, 27157
About this study
Official title: The Safety, Pharmacokinetics, and Pharmacodynamic Effects of TNX-832 (Sunol cH36) in Subjects With Acute Lung Injury/Acute Respiratory Distress Syndrome
This Phase I/IIa, multi-center, randomized, placebo-controlled, single-blinded dose-escalation study evaluated TNX-832 (also referred to as ALT-836 and Sunol cH36) in subjects with suspected or proven bacteria-induced ALI/ARDS. Up to five cohorts of at least six subjects each were originally planned. Subjects were to be randomized in a 5:1 ratio to receive TNX-832 or placebo,respectively, administered as a single bolus infusion over 15 minutes. Three cohorts of subjects were enrolled to the study and safety and pharmacokinetics of the study treatment were evaluated.
Read the detailed description
Tissue factor (TF) is a transmembrane glycoprotein that acts as the principal initiator of the extrinsic coagulation pathway. TF is a key mediator between the immune system and coagulation and is the principal activator of coagulation. The TF-FVIIa complex activates FX and FIX, resulting in the cleavage of prothrombin to thrombin. Normally, localized activation of the coagulation cascade associated with inflammatory responses plays a role in controlling the spread of infectious agents; however, aberrant TF expression often leads to serious thrombotic disorders. TF-dependent thrombosis has been associated with many diseases including septic shock, coronary artery disease (CAD), cancer, and many inflammatory and autoimmune disorders such as lupus, rheumatoid arthritis, psoriasis, and inflammatory bowel disease.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are forms of acute respiratory failure characterized by diffuse pulmonary infiltrates, pulmonary hypertension, refractory hypoxemia, loss of pulmonary compliance and normal hydrostatic pressures. ALI and ARDS commonly occur in patients with acute catastrophic events such as sepsis, trauma and severe pulmonary infections. The incidence of ALI and ARDS is extremely high in patients with sepsis. By blocking the initiating events of extrinsic coagulation activation, their effects on pro-inflammatory events in the lungs and disordered fibrin deposition may be corrected and the evolution of severe structural and functional injury may be averted during ALI/ARDS. TNX-832 (formerly known as Sunol-cH36), directed against human TF, which can block the pathological complications of TF-dependent thrombus formation. The blockage by TNX-832 of initiating events in the extrinsic coagulation pathway may attenuate the effects on pro-inflammatory events in ALI/ARDS patients, thereby averting or decreasing disordered fibrin deposition and averting the evolution of severe structural and functional injury.
- Being tested
- TNX-832, Placebo
- Keywords
- Sepsis, Acute Lung Injury, Acute Respiratory Distress Syndrome, ALI/ARDS, Lung Disease
- Medical subject headings
- Sepsis, Acute Lung Injury, Respiratory Distress Syndrome, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNX-832Biological
Also called ALT-836, Sunol cH36
Single intravenous dose of TNX-832 at 0.06, 0.08 or 0.10 mg/kg
PlaceboDrug
Single intravenous dose of saline control
| Study group | Role | What they receive |
|---|---|---|
| TNX-832 | Experimental | Anti-tissue factor antibody Receives: Biological: TNX-832 |
| Drug Placebo | Placebo comparator | Placebo control Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
To evaluate the safety of escalating dose levels of TNX-832 in subjects with suspected or proven bacteria-induced ALI/ARDS. Safety was assessed by number of treatment emergent adverse events, and changes in vital signs, ECGs, laboratory, coagulation and pulmonary function parameters from baseline. Immunogenicity (serum anti-TNX-832 antibody response) was evalutated.
Measured: Up to 4 weeks
Cmax
maximum observed concentration (Cmax)
Measured: predose; 15 and 30 min; 1, 4, 6, 12 and 24 hrs; 2, 3, 4, 5, 6, and 7 days, 2, 3, 4 weeks
AUCinf and AUClast
Area under the plasma concentration curve from time 0 extrapolated to infinite time (AUC0-inf).
AUClast (area under the serum concentration-time curve from the time of dosing to the time of the last observed concentration).
Measured: Up 163.3 hours
Terminal t1/2 and Tmax
t1/2 (terminal elimination phase half life). Tmax (time to maximum serum concentration).
Measured: predose; 15 and 30 min; 1, 4, 6, 12 and 24 hrs; 2, 3, 4, 5, 6, and 7 days, 2, 3, 4 weeks
Vd and Vss
Volume of distribution (Vd) based on the terminal elimination phase, also referred to as VZ; in mL/kg.
Volume of distribution at steady state (Vss), calculated as the Mean residence Time times Clearance; in mL/kg.
Measured: predose; 15 and 30 min; 1, 4, 6, 12 and 24 hrs; 2, 3, 4, 5, 6, and 7 days, 2, 3, 4 weeks
Cl
Total body clearance, CL=Dose/AUC; in mL/hr/kg
Measured: up to 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2011 (estimated)
- Study startDec 2004
- Primary completionJul 2006
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Altor BioScience
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc., Tanox
- Responsible party
- Sponsor
- Investigators
- Hing Wong, PhD, Study director, Altor BioScience
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01438853
- Sponsor's protocol ID
- TNX-832.201
- Status last verified
- Aug 2024
- First submitted
- 20 Sep 2011
- Last updated
- 6 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Morris PE, Steingrub JS, Huang BY, Tang S, Liu PM, Rhode PR, Wong HC. A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome. BMC Pulm Med. 2012 Feb 16;12:5. doi: 10.1186/1471-2466-12-5.
PubMed 22340260
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety, Pharmacokinetics, and Pharmacodynamic Effects of TNX-832 (Sunol cH36) in Subjects With Acute Lung Injury/Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT01438853
- Acronym / sponsor ID
- TNX-832.201
- Keywords
- Sepsis, Acute Lung Injury, Acute Respiratory Distress Syndrome, ALI/ARDS, Lung Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Altor BioScienceIndustry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc., Tanox
- Study start
- Dec 2004
- Primary completion
- Jul 2006 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 22 Sep 2011 (estimated)
- Results
- Posted 6 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase I/IIa, multi-center, randomized, placebo-controlled, single-blinded dose-escalation study evaluated TNX-832 (also referred to as ALT-836 and Sunol cH36) in subjects with suspected or proven bacteria-induced ALI/ARDS. Up to five cohorts of at least six subjects each were originally planned. Subjects were to be randomized in a 5:1 ratio to receive TNX-832 or placebo,respectively, administered as a single bolus infusion over 15 minutes. Three cohorts of subjects were enrolled to the study and safety and pharmacokinetics of the study treatment were evaluated.
Detailed description
Tissue factor (TF) is a transmembrane glycoprotein that acts as the principal initiator of the extrinsic coagulation pathway. TF is a key mediator between the immune system and coagulation and is the principal activator of coagulation. The TF-FVIIa complex activates FX and FIX, resulting in the cleavage of prothrombin to thrombin. Normally, localized activation of the coagulation cascade associated with inflammatory responses plays a role in controlling the spread of infectious agents; however, aberrant TF expression often leads to serious thrombotic disorders. TF-dependent thrombosis has been associated with many diseases including septic shock, coronary artery disease (CAD), cancer, and many inflammatory and autoimmune disorders such as lupus, rheumatoid arthritis, psoriasis, and inflammatory bowel disease.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are forms of acute respiratory failure characterized by diffuse pulmonary infiltrates, pulmonary hypertension, refractory hypoxemia, loss of pulmonary compliance and normal hydrostatic pressures. ALI and ARDS commonly occur in patients with acute catastrophic events such as sepsis, trauma and severe pulmonary infections. The incidence of ALI and ARDS is extremely high in patients with sepsis. By blocking the initiating events of extrinsic coagulation activation, their effects on pro-inflammatory events in the lungs and disordered fibrin deposition may be corrected and the evolution of severe structural and functional injury may be averted during ALI/ARDS. TNX-832 (formerly known as Sunol-cH36), directed against human TF, which can block the pathological complications of TF-dependent thrombus formation. The blockage by TNX-832 of initiating events in the extrinsic coagulation pathway may attenuate the effects on pro-inflammatory events in ALI/ARDS patients, thereby averting or decreasing disordered fibrin deposition and averting the evolution of severe structural and functional injury.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TNX-832 | Experimental | Biological: TNX-832Anti-tissue factor antibody |
| Drug Placebo | Placebo comparator | Drug: PlaceboPlacebo control |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- ≥ 18 years
- Suspected or proven bacterial infection
- Receiving positive pressure ventilation through an endotracheal tube
- Have ALI/ARDS, defined as having all of the following:
- Provide signed informed consent
Key exclusion criteria (48 listed)
- Mechanically or chemically-induced ALI/ARDS (including burns, trauma, and near drowning)
- End-stage lung disease
- Decompensated congestive heart failure
- Authorization to withdraw life support
- Hemoglobin persistently <8.0 g/dL
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TNX-832Also: ALT-836, Sunol cH36Single intravenous dose of TNX-832 at 0.06, 0.08 or 0.10 mg/kg | Biological | TNX-832 |
| PlaceboSingle intravenous dose of saline control | Drug | Drug Placebo |
Primary outcome
Number of Participants With Adverse Events
Time frame: Up to 4 weeks
To evaluate the safety of escalating dose levels of TNX-832 in subjects with suspected or proven bacteria-induced ALI/ARDS. Safety was assessed by number of treatment emergent adverse events, and changes in vital signs, ECGs, laboratory, coagulation and pulmonary function parameters from baseline. Immunogenicity (serum anti-TNX-832 antibody response) was evalutated.
Cmax
Time frame: predose; 15 and 30 min; 1, 4, 6, 12 and 24 hrs; 2, 3, 4, 5, 6, and 7 days, 2, 3, 4 weeks
maximum observed concentration (Cmax)
AUCinf and AUClast
Time frame: Up 163.3 hours
Area under the plasma concentration curve from time 0 extrapolated to infinite time (AUC0-inf). AUClast (area under the serum concentration-time curve from the time of dosing to the time of the last observed concentration).
Terminal t1/2 and Tmax
Time frame: predose; 15 and 30 min; 1, 4, 6, 12 and 24 hrs; 2, 3, 4, 5, 6, and 7 days, 2, 3, 4 weeks
t1/2 (terminal elimination phase half life). Tmax (time to maximum serum concentration).
Vd and Vss
Time frame: predose; 15 and 30 min; 1, 4, 6, 12 and 24 hrs; 2, 3, 4, 5, 6, and 7 days, 2, 3, 4 weeks
Volume of distribution (Vd) based on the terminal elimination phase, also referred to as VZ; in mL/kg. Volume of distribution at steady state (Vss), calculated as the Mean residence Time times Clearance; in mL/kg.
Cl
Time frame: up to 1 week
Total body clearance, CL=Dose/AUC; in mL/hr/kg
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22340260Morris PE, Steingrub JS, Huang BY, Tang S, Liu PM, Rhode PR, Wong HC. A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome. BMC Pulm Med. 2012 Feb 16;12:5. doi: 10.1186/1471-2466-12-5.
- Related InfoLink provided by the sponsor.
Related trials for Sepsis
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hing Wong, PhD study director
Altor BioScience
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TNX-832 in people with Sepsis and Acute Lung Injury, run by Altor BioScience at 7 sites in 2 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 8 inclusion and 48 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 6 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada. 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 phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 6 Jan 2025). 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?
Number of Participants With Adverse Events (time frame: Up to 4 weeks). The study lists 6 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 NCT01438853, which also lists 1 linked publication.
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 6 Jan 2025.