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Trial record 1 of 1 for:    tnt009
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Safety, Tolerability and Activity of TNT009 in Healthy Volunteers and Patients With Complement Mediated Disorders (TNT009-01)

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by True North Therapeutics
Sponsor:
Collaborators:
Assign Clinical Research GmbH
Assign Data Management and Biostatistics GmbH
Vela Laboratories
ABF Pharmaceutical Services GmbH
Quest Diagnostics
Information provided by (Responsible Party):
True North Therapeutics
ClinicalTrials.gov Identifier:
NCT02502903
First received: July 7, 2015
Last updated: April 24, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Bullous Pemphigoid (BP) Cold Agglutinin Disease Warm Autoimmune Hemolytic Anemia End-stage Renal Disease (ESRD) Drug: TNT009 Other: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by True North Therapeutics:

Primary Outcome Measures:
  • Drug-related Adverse Event profile of TNT009 [ Time Frame: 6 weeks ]
    Serious and Non-Serious adverse events probably or possibly attributable to TNT009


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 98
Study Start Date: June 2015
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: June 17, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Part A
SAD in NHVs, 7 cohorts, TNT009 by IV infusion (0.3,1, 3, 10, 30, 60, or 100 mg/kg) or placebo.
Drug: TNT009 Other: Placebo
Other Name: saline solution 0,9 %
Placebo Comparator: Part B
MAD in NHVs, 4 weekly IV doses of TNT009 (30 or 60mg/kg) or placebo
Drug: TNT009 Other: Placebo
Other Name: saline solution 0,9 %
Experimental: Part C
multiple dose in a single cohort of patients with various complement-mediated disorders. All patients in Part C will receive a single IV test dose of 10 mg/kg followed by 4 weekly doses of 60 mg/kg.
Drug: TNT009

Detailed Description:
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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Part A/B:

  • healthy male or female volunteers, age ≥ 18 years old
  • if female, must be post-menopausal, surgically sterilized, or willing/able to use dual, redundant methods of contraception (e.g., barrier plus oral contraceptives) throughout the study
  • previously vaccinated against encapsulated bacterial pathogens (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) or willing to undergo vaccination
  • able to comprehend and to give informed consent
  • able to co-operate with the investigator, to comply with the requirements of the study, and to complete the full sequence of protocol-related procedures

Part C:

  • male or female, age ≥ 18 years old
  • if female, must be post-menopausal, surgically sterilized, or willing/able to use dual, redundant methods of contraception (e.g., barrier plus oral contraceptives) throughout the study
  • previously vaccinated against encapsulated bacterial pathogens (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) or willing to undergo vaccination
  • able to comprehend and to give informed consent
  • able to co-operate with the investigator, to comply with the requirements of the study, and to complete the full sequence of protocol-related procedures
  • History of one of the following complement-mediated disorders:

    • bullous pemphigoid (BP)
    • cold agglutinin disease (CAD)
    • warm autoimmune hemolytic anemia (WAIHA)
    • active Antibody-Mediated Rejection (AMR) (acute or chronic) after kidney transplantation
  • If CAD, by medical history within the 3 months preceding enrollment, and again at the screening visit:

    o Has hemoglobin < 11.0 g/dL

  • If AMR:

    • is ≥ 180 days post-kidney transplantation with biopsy-proven late AMR
    • has a functioning kidney graft with eGFR ≥ 20ml/min/1.73m2
    • has evidence of late, active AMR (acute or chronic) present on renal allograft biopsy:
    • molecular signature indicating AMR (molecular AMR score > 0.2)
    • morphological and immunohistochemical findings consistent with AMR according to the criteria of the Banff 2013 classification
    • morphological findings consistent with an active rejection process: presence of glomerulitis (g score > 0) and / or peritubular capillaritis (ptc score > 0)
    • has IgG type DSA present in serum (at time of renal allograft biopsy) with MFI > 1000 in single antigen bead assays
    • is willing and able to take routine antibiotic prophylaxis with ciprofloxacin

Exclusion Criteria:

Part A/B:

  • clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the subject or compromise the quality of the data derived from his/her participation in this study
  • clinically relevant infection of any kind within the preceding month
  • clinically relevant abnormal findings on physical examination or clinically relevant laboratory abnormalities
  • history of infusion hypersensitivity, allergic or anaphylactic reactions to other therapeutic proteins
  • substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the Investigator for the subject to be able to comply fully with study procedures
  • use of medication during 2 weeks before the start of the study, which in the judgment of the investigator may adversely affect the subject's welfare or the integrity of the study's results (excluding hormonal contraception in female subjects)
  • females who are pregnant (positive pregnancy test at screening or during study phase), lactating, or, if having reproductive potential, are considered potentially unreliable with respect to contraceptive practice
  • concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to treatment start
  • body weight > 98 kg for all subjects in all dose cohorts other than the 100 mg/kg dose cohort of Part A, for which the body weight upper limit is 58 kg

Part C:

  • active acute or chronic viral, bacterial, fungal, or mycobacterial infection, or history of same within preceding month
  • autoimmune disorder other than the complement-mediated disorders listed in the Inclusion Criteria
  • known malignancy (other than locally limited, previously surgically removed basal cell carcinoma of the skin, lymphoproliferative disorders causally related to the complement-mediated diseases under study, etc.)
  • clinically significant hepatobiliary disorder
  • history of infusion hypersensitivity, allergic or anaphylactic reactions to other therapeutic proteins
  • substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the Investigator for the subject to be able to comply fully with study procedures
  • females who are pregnant (positive pregnancy test at screening or during study phase), lactating, or, if having reproductive potential, are considered potentially unreliable with respect to contraceptive practice
  • concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to treatment start
  • body weight >98 kg
  • Solely for kidney transplantation patients with AMR:

    • acute graft dysfunction within preceding 1 month
    • rejection treatment within preceding 1 month
    • morphological or molecular features of T cell-mediated rejection on renal allograft biopsy
    • contraindication to ciprofloxacin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02502903

Contacts
Contact: Sabine Schranz +4314040029810 sabine.schranz@meduniwien.ac.at

Locations
Austria
Medical University of Vienna Recruiting
Vienna, Austria, 1090
Contact: Sabine Schranz    +43 1 40400 29810    sabine.schranz@meduniwien.ac.at   
Contact: Bernd Jilma, Prof. Dr.    +43 1 40400 29810    bernd.jilma@meduniwien.ac.at   
Sponsors and Collaborators
True North Therapeutics
Assign Clinical Research GmbH
Assign Data Management and Biostatistics GmbH
Vela Laboratories
ABF Pharmaceutical Services GmbH
Quest Diagnostics
Investigators
Principal Investigator: Bernd Jilma, Prof. Dr. Medical University of Vienna
  More Information

Responsible Party: True North Therapeutics
ClinicalTrials.gov Identifier: NCT02502903     History of Changes
Other Study ID Numbers: TNT009-01
Study First Received: July 7, 2015
Last Updated: April 24, 2017

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Pemphigoid, Bullous
Anemia, Hemolytic
Anemia, Hemolytic, Autoimmune
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Anemia
Hematologic Diseases
Complement System Proteins
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 23, 2017