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Graft vs Host DiseasePhase 1/2NCT02027805

Safety and Efficacy Study of T-Guard to Treat Steroid-resistant Acute GVHD

A Phase 1/2 study testing T-Guard in people with Graft vs Host Disease, run by Xenikos at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In this study, a combination of two antibodies both conjugated to a cell-killing toxin (so-called immunotoxins) will be evaluated. The antibodies are directed against T-cell antigens 'cluster of differentiation 3 antigen' (CD3) and CD7. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft vs Host Disease
What is being tested?
T-Guard
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
2 sitesin 2 countries
Study dates
5 Mar 2014to 3 Nov 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Patients suffering from acute GVHD which is staged Grade II-IV according to the modified Glucksberg Criteria and progressing after 3 days, or not improving after 7 days, of methylprednisolone at a dose of 2 mg/kg per day.
  • Age ≥18 years.
  • Patients or an impartial witness (in case the patient is capable to provide verbal consent but not capable to sign the informed consent) should have given written informed consent.

Who cannot join

  • Patients receiving concomitant investigational therapeutics for acute GVHD, including investigational agents used for GVHD prophylaxis, at the time of enrollment.
  • Patients with signs or symptoms suggestive of chronic GVHD.
  • Patients requiring mechanical ventilation, requiring vasopressor support, requiring hemodialysis, having serum creatinine > 266 µmol/l (> 3 mg/dl), or having a serum albumin level of 15 g/l or less.
  • Patients having uncontrolled bacterial, viral or fungal infections, at the discretion of the investigator, at the start of therapy.
  • Patients with current signs or symptoms of active intrapulmonary disease.
  • Patients with known hypersensitivity to any of the components of the study drug.
Show all 10Show fewer
  • Female patients who are pregnant, breast feeding, or, if sexually active, unwilling to use effective birth control for the duration of the study.
  • Male patients who are, if sexually active, unwilling to use effective birth control for 30 days after the last infusion.
  • Patients participating in a clinical trial with another investigational product within 30 days prior to providing informed consent.
  • Patients whose decision to participate might be unduly influenced by perceived expectation of gain or harm by participation, such as patients in detention due to official or legal order.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Germany1 site

  • University Hospital Münster

    Münster, North Rhine-Westphalia, 48149

Other trials in Germany

Netherlands1 site

  • Radboudumc

    Nijmegen, Gelderland, 6525 GA

Other trials in Netherlands

About this study

Official title: A Phase I/II Multicentric Study to Determine the Safety and Efficacy of a Combination of Anti-CD3 & Anti-CD7 Ricin A Immunotoxins (T-Guard) for the Treatment of Steroid-resistant Acute Graft-versus-Host Disease.

In this study, a combination of two antibodies both conjugated to a cell-killing toxin (so-called immunotoxins) will be evaluated. The antibodies are directed against T-cell antigens 'cluster of differentiation 3 antigen' (CD3) and CD7. Previous in vitro studies have demonstrated that this particular immunotoxin-combination, named T-Guard, acts synergistically in eliminating T cells with a preference for killing activated T-cells. In a subsequent clinical pilot-study, T-Guard has generated encouraging results when applied as third-line therapy for patients suffering form steroid-resistant acute Graft-versus-Host Disease (GVHD). Extensive biological and clinical responses could be noted in the absence of severe acute toxicities. Building on these results, the current study aims at evaluating the safety and efficacy of T-Guard for treating steroid-resistant GVHD when administered in an earlier phase of the disease process, i.e. as second-line instead of as third-line therapy.

Read the detailed description

The experimental design is a bicentric non-controlled fixed-dose Phase I/II study. A total of 20 adult patients with acute steroid-resistant GVHD will be enrolled in a 12 months period. The treatment consists of a standard dose of 4 infusions T-Guard (4 mg/m2), given 48-hours apart over a 4-hour period. The intended follow-up period is 6 months.

The primary objective is to determine the efficacy of T-Guard, 4 weeks after the first infusion (Day 28), in inducing an objective clinical response in patients with acute GVHD refractory to standard first line corticosteroid therapy.

Secondary objectives are:

  • To evaluate the overall safety and efficacy of T-Guard during the first 6 months after imitation of therapy;
  • To determine the pharmacokinetic profile of T-Guard;
  • To determine the immunogenicity of T-Guard.

Exploratory objectives are:

  • To study the specificity and kinetics of the treatment-induced depletion and subsequent repopulation of lymphocyte subsets;
  • To evaluate diagnostic and predictive GVHD biomarkers relative to treatment outcomes.
Being tested
T-Guard
Keywords
Steroid-resistant, Graft vs Host Disease, Refractory acute Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Stem Cell Transplantation, Allogeneic Stem Cell Transplantation, Immune System Diseases, Antibodies, monoclonal, Immunotoxins, Immunosuppressive agents
Medical subject headings
Graft vs Host Disease, Immune System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • T-GuardBiological

    Also called Combination of SPV-T3a-RTA and WT1-RTA (equal parts, w/w)

Study groups in NCT02027805
Study groupRoleWhat they receive
T-GuardExperimentalFour doses of T-Guard (4 mg/m2), administered at 48-hour intervals as 4 hour infusions.
Receives: Biological: T-Guard

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Acute GVHD response rate

    The acute GVHD response rate at 4 weeks after the first injection of T-Guard (Day 28), being defined as as the fraction of patients showing a complete or partial response (CR or PR)

    Measured: Day 28

Secondary outcomes (8)

  1. Safety and tolerability of T-Guard

    The safety and tolerability of T-Guard as assessed by evaluating Dose Limiting Toxicities (DLT's), adverse and serious adverse events reported during 6 months after initiation of treatment.

    Measured: During 6 months after initiation of treatment

  2. Very good partial response rate

    The proportion of patients achieving a very good partial response rate (VGPR) of their acute GVHD at 4 weeks after the first infusion (Day 28).

    Measured: Day 28

  3. Acute GVHD relapse rate

    Measured: During 6 months after initiation of therapy

  4. Incidence of chronic GVHD

    Measured: During 6 months after initiation of therapy

  5. Overall survival and progression free survival

    Measured: During 6 months after initiation of treatment

  6. Pharmacokinetic profile of T-Guard

    • Areas under the time-concentration curves (AUC);
    • Peak concentration (Cmax);
    • Time to peak concentration (Tmax);
    • Terminal-phase elimination half-life (t1/2);
    • Apparent Clearance (CL/F);
    • Steady-state volume of distribution (Vss/F).

    Measured: Up to Day 9

  7. Anti-drug-antibodies

    The occurrence and extent of humoral responses against T-Guard (anti-drug-antibodies, ADA).

    Measured: Pre-treatment, Day 14, Day 28, Day 90, and Day 180

  8. The occurrence of treatment-induced cytokine release

    The occurrence of treatment-induced cytokine release, as determined by measurement of interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-a), and interferon-gamma (IFN-g) serum levels at t = 0 (pre-dose), 1 and 4 hours after starting of each infusion.

    Measured: Day 1, 3, 5, and 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2014 (estimated)
  2. Study start5 Mar 2014
  3. Primary completion7 Sep 2016
  4. Study completion3 Nov 2016

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02027805
Sponsor's protocol ID
XEN/TG-001
Other IDs
2013-000068-27
Status last verified
Jun 2017
First submitted
3 Jan 2014
Last updated
6 Jun 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing T-Guard in people with Graft vs Host Disease, run by Xenikos at 2 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 3 inclusion and 10 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 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany, Netherlands. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Acute GVHD response rate (time frame: Day 28). 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 NCT02027805.

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 Jun 2017.

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