Clinical Trial: Safety, Tolerability and Activity of TNT009 in Healthy Volunteers and Patients With Complement Mediated Disorders

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Safety, Tolerability and Activity of TNT009 in Healthy Volunteers and Patients With Complement-mediated Disorders. A Single/Multiple Ascending Dose Phase 1 Study

Brief Summary: Prospective, double-blind, randomized, placebo-controlled First-In-Human study with three sub-parts: Part A, a single ascending dose study (SAD) in normal human volunteers (NHVs), Part B, a multiple ascending dose study (MAD) in NHVs, Part C, a multiple dose (MD) study in patients with a complement-mediated disorder.

Detailed Summary: Study TNT009-01 is a First in Human (FIH) study that uses an Integrated Protocol Design. This Phase 1 study protocol will comprise three sub-parts: a Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) study in normal male and female human volunteers (NHVs), and a Multiple Dose (MD) study in patients with various complement-mediated disorders not confined to a single disease or therapeutic area. Although these patients represent a population with a diverse set of clinical diagnoses they are united by a common mechanism of disease matched to the mechanism of action of TNT009. Several key safety measures have been incorporated into the design of this study, including use of Sentinel Dosing Groups and an independent Data Safety Monitoring Board (DSMB), as well as an appropriate program of prophylactic vaccinations and clinical biomarker surveillance related to the risks potentially associated with inhibition of the complement system.
Sponsor: True North Therapeutics

Current Primary Outcome: Drug-related Adverse Event profile of TNT009 [ Time Frame: 6 weeks ]

Serious and Non-Serious adverse events probably or possibly attributable to TNT009


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Pharmacokinetic profile of TNT009 [ Time Frame: 6 weeks ]
    Tmax, Cmax, AUC and T1/2
  • Classical pathway complement system activity [ Time Frame: 6 weeks ]
    inhibition by TNT009 of the complement system classical pathway measured by the WIESLAB® assay
  • Complement System-Related biomarkers [ Time Frame: 6 weeks ]
    e.g. CH50
  • Coagulation System-Related biomarkers [ Time Frame: 6 weeks ]
    e.g. Fibrin D-dimer
  • Disease-Related Biomarkers [ Time Frame: 6 weeks ]
    e.g. Haptoglobin


Original Secondary Outcome:

  • Pharmacokinetic profile of TNT009 [ Time Frame: 6 weeks ]
    Tmax, Cmax, AUC and T1/2
  • Classical pathway complement system activity [ Time Frame: 6 weeks ]
    inhibition by TNT009 of the complement system classical pathway measured by the WIESLAB® assay
  • Complement System-Related biomarkers [ Time Frame: 6 weeks ]
    various measures of Complement System activity (including Complement System Alternative Pathway WIESLAB, CH50, C4, etc.)
  • Coagulation System-Related biomarkers [ Time Frame: 6 weeks ]
    Fibrin D-dimer, Prothrombin Fragment F1.2, Fibrinopeptide A
  • Disease-Related Biomarkers [ Time Frame: 6 weeks ]
    Cold Agglutinin titer in sera from CAD patients, Haptoglobin (plus routine clinical lab parameters of hemolysis, e.g. hemoglobin, hematocrit, reticulocyte count, LDH, bilirubin) in blood samples from WAIHA and CAD patients, Ex vivo C3b deposition on normal donor RBCs exposed to sera from CAD and WAIHA patients, Anti-BP-180 titer in sera from BP patients, Anti-BP-230 titer in sera from BP patients, Ex vivo C3d deposition on normal donor skin patches exposed to sera from BP patients, Anti-HLA antibody titer in sera from ESRD patients


Information By: True North Therapeutics

Dates:
Date Received: July 7, 2015
Date Started: June 2015
Date Completion: October 2018
Last Updated: April 24, 2017
Last Verified: April 2017