Proof-of-concept Trial of Apraglutide in GVHD
- Registration Number
- NCT05415410
- Lead Sponsor
- VectivBio AG
- Brief Summary
The aim of this trial is to assess safety and efficacy of apraglutide in subjects with steroid refractory gastrointestinal acute graft versus host disease (aGVHD).
- Detailed Description
This is an international, multicenter, randomized proof-of-concept trial to evaluate safety, tolerability, efficacy, durability of response, and clinical outcomes of apraglutide administration to subjects with steroid-refractory (SR) aGVHD of the lower GI tract being treated with systemic steroids (SS) and ruxolitinib (RUX).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 31
- Able to give informed consent and agree to follow the details of participation as outlined in the protocol
- Male or female subjects aged 12 years or above at the time of consent and who weigh a minimum of 40 kg. Only subjects aged 18 years and above will be included in Germany.
- Clinically confirmed steroid refractory lower GI-aGVHD (MAGIC stage 1-4) prior to randomization
- Have undergone alloSCT from any donor source, any conditioning regimen
- Treated with SS plus RUX (RUX starts concomitantly to apraglutide or a maximum of 72 hours before apraglutide initiation)
- Women of childbearing potential (WOCBP): highly effective method of contraception and refrain from donating eggs during the trial and for 4 weeks after the End of Trial (EOT) visit
- Male subjects with partner WOCBP: contraception and abstention from sperm donation during the trial and for 2 weeks after the EOT visit
- Treatment with any systemic GVHD therapy other than SS and RUX including methotrexate and mycophenolate mofetil at the time of randomization / Day 0
- Concomitant treatment with Janus kinase inhibitor other than RUX at the time of randomization
- Failed alloSCT due to relapse of underlying malignant disease
- Presence of SR GI-aGVHD occurring after donor lymphocyte infusion for pre-emptive treatment of malignancy recurrence
- Any use of enteral glutamine or GLP analogs or known ADA, within 6 months prior to randomization / Day 0
- Significant organ system failures (respiratory renal hepatic and cardiac)
- Presence of relapsed primary malignancy or treatment for relapse after alloHSCT
- Presence or history of GI tumors (including the hepatobiliary system and pancreas) within the last five years before randomization
- Presence of colonic polyps not removed
- Active clinically uncontrolled infection or active tuberculosis
- Known chronic GVHD
- Known active GI inflammation not related to GI-aGVHD
- Major abdominal surgery in the last 6-months prior to randomization or history of clinically significant intestinal adhesions
- Abnormal liver function tests
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Apraglutide Standard Dose Apraglutide Apraglutide SC injections, once weekly, for subjects with body weight between 40.0 kg to 49.9 kg. Apraglutide Low Dose Apraglutide Apraglutide SC injections, once weekly, for subjects with body weight of more than 50.0 kg. Apraglutide High Dose Apraglutide Apraglutide SC injections, once weekly, for subjects with body weight of more than 50.0 kg.
- Primary Outcome Measures
Name Time Method Adverse events (AE) From baseline to week 104 System organ class, frequency and severity
Occurrence of clinically relevant changes in electrocardiogram From baseline to week 104 ECG rhythm
Occurrence of clinically relevant changes in vital signs From baseline to week 104 Heart rate in Beats per Minute (BPM)
Occurrence and titer anti-drug antibodies (ADA) From baseline to week 104 Number of subjects with anti-drug antibodies and their respective titers at specific time points.
- Secondary Outcome Measures
Name Time Method Graft failure post-first dose of apraglutide Baseline to 2 years Incidence of graft failure
Lower Gastrointestinal-GVHD relapse following complete GI response Baseline to 2 years Incidence of lower Gastrointestinal-aGVHD relapse following complete GI-response. Number of relapses Relapse is defined as GI flare: any increase in signs or symptoms of lower GI-aGVHD that is sustained for \>24 h after an initial response (complete response or initial response) and requires re-escalation of immunosuppressive therapy.
Overall response At days 14, 28, 56, 91, 119, 147, and 182 Overall response will be measured as a change of MAGIC stage in any of the 4 organ systems.
Measurement: MAGIC stage from 0 to 4Failure free survival post-first dose of apraglutide Baseline to 2 years The time from the date of randomization to the date of hematologic disease relapse/progression, non-relapse mortality, or addition of new systemic aGVHD treatment.
Unit: daysMalignancy relapse/progression post-first dose of apraglutide Baseline to 2 years The time from date of randomization to hematologic disease relapse/progression. Unit:days
Apparent volume of distribution (Vz/F) of apraglutide through population PK data analysis Day 7 to day 56 Absorption rate constant (ka) of apraglutide through population PK data analysis Day 7 to day 56 Overall survival post-first dose of apraglutide Baseline to 2 years Apparent clearance (CL/F) of apraglutide through population PK data analysis Day 7 to day 56 Lower gastrointestinal-aGVHD response At Days 14, 28, 56, 91, 119, 147, and 182 Gastrointestinal-aGVHD response will be measured as a change of MAGIC stage for lower GI.
Unit: Number of stools/day
Trial Locations
- Locations (13)
The Ohio State University
🇺🇸Columbus, Ohio, United States
Universitätsmedizin der Johannes Gutenberg - Universität Mainz
🇩🇪Mainz, Germany
Universitaetsklinikum Duesseldorf
🇩🇪Düsseldorf, Germany
South Austin Medical Center
🇺🇸Austin, Texas, United States
Instituto Portugues de Oncologia do Porto Francisco Gentil
🇵🇹Porto, Portugal
Universitätsklinikum Köln (AoeR)
🇩🇪Köln, Germany
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
University of Iowa
🇺🇸Iowa City, Iowa, United States
Martin Luther Universität Halle-Wittenberg
🇩🇪Halle, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany