Proof-of-concept Trial of Apraglutide in GVHD
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ClinicalTrials.gov Identifier: NCT05415410 |
Recruitment Status :
Active, not recruiting
First Posted : June 13, 2022
Last Update Posted : January 9, 2024
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Condition or disease | Intervention/treatment | Phase |
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GVHD | Drug: Apraglutide | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 31 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Single (Participant) |
Primary Purpose: | Treatment |
Official Title: | A Randomized, Single-blind Trial to Evaluate the Safety and Efficacy of Apraglutide in Subjects With Grade II to IV (MAGIC) Steroid Refractory Gastrointestinal (GI) Acute Graft Versus Host Disease on Best Available Therapy |
Actual Study Start Date : | May 25, 2022 |
Estimated Primary Completion Date : | August 30, 2025 |
Estimated Study Completion Date : | August 30, 2025 |
Arm | Intervention/treatment |
---|---|
Experimental: Apraglutide Low Dose
Apraglutide SC injections, once weekly, for subjects with body weight of more than 50.0 kg.
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Drug: Apraglutide
Apraglutide is a new, synthetic glucagon-like peptide 2 (GLP-2) receptor agonist which acts as a gut targeted regenerative approach that is intestinotrophic with a mode of action that improves absorption and enhances gut barrier function. |
Experimental: Apraglutide High Dose
Apraglutide SC injections, once weekly, for subjects with body weight of more than 50.0 kg.
|
Drug: Apraglutide
Apraglutide is a new, synthetic glucagon-like peptide 2 (GLP-2) receptor agonist which acts as a gut targeted regenerative approach that is intestinotrophic with a mode of action that improves absorption and enhances gut barrier function. |
Experimental: Apraglutide Standard Dose
Apraglutide SC injections, once weekly, for subjects with body weight between 40.0 kg to 49.9 kg.
|
Drug: Apraglutide
Apraglutide is a new, synthetic glucagon-like peptide 2 (GLP-2) receptor agonist which acts as a gut targeted regenerative approach that is intestinotrophic with a mode of action that improves absorption and enhances gut barrier function. |
- Adverse events (AE) [ Time Frame: From baseline to week 104 ]System organ class, frequency and severity
- Occurrence of clinically relevant changes in vital signs [ Time Frame: From baseline to week 104 ]Systolic and diastolic blood pressure in mmHg
- Occurrence of clinically relevant changes in vital signs [ Time Frame: From baseline to week 104 ]Heart rate in Beats per Minute (BPM)
- Occurrence of clinically relevant changes in electrocardiogram [ Time Frame: From baseline to week 104 ]ECG QT Interval
- Occurrence of clinically relevant changes in electrocardiogram [ Time Frame: From baseline to week 104 ]ECG PR interval
- Occurrence of clinically relevant changes in electrocardiogram [ Time Frame: From baseline to week 104 ]ECG QRS interval
- Occurrence of clinically relevant changes in electrocardiogram [ Time Frame: From baseline to week 104 ]ECG rhythm
- Occurrence and titer anti-drug antibodies (ADA) [ Time Frame: From baseline to week 104 ]Number of subjects with anti-drug antibodies and their respective titers at specific time points.
- Lower gastrointestinal-aGVHD response [ Time Frame: 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
- Overall response [ Time Frame: 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 4
- Graft failure post-first dose of apraglutide [ Time Frame: Baseline to 2 years ]Incidence of graft failure
- Failure free survival post-first dose of apraglutide [ Time Frame: 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: days
- Overall survival post-first dose of apraglutide [ Time Frame: Baseline to 2 years ]
- Malignancy relapse/progression post-first dose of apraglutide [ Time Frame: Baseline to 2 years ]The time from date of randomization to hematologic disease relapse/progression. Unit:days
- Lower Gastrointestinal-GVHD relapse following complete GI response [ Time Frame: 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.
- Absorption rate constant (ka) of apraglutide through population PK data analysis [ Time Frame: Day 7 to day 56 ]
- Apparent clearance (CL/F) of apraglutide through population PK data analysis [ Time Frame: Day 7 to day 56 ]
- Apparent volume of distribution (Vz/F) of apraglutide through population PK data analysis [ Time Frame: Day 7 to day 56 ]
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Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05415410
United States, California | |
Stanford Cancer Center | |
Stanford, California, United States, 94305 | |
United States, Iowa | |
University of Iowa | |
Iowa City, Iowa, United States, 52242 | |
United States, Massachusetts | |
Massachusetts General Hospital | |
Boston, Massachusetts, United States, 02114 | |
United States, Ohio | |
The Ohio State University | |
Columbus, Ohio, United States, 43210 | |
United States, Texas | |
South Austin Medical Center | |
Austin, Texas, United States, 78704 | |
Germany | |
Universitaetsklinikum Duesseldorf | |
Düsseldorf, Germany, 40225 | |
Universitätsklinikum Freiburg | |
Freiburg, Germany, 79106 | |
Martin Luther Universität Halle-Wittenberg | |
Halle, Germany, 06120 | |
Universitätsklinikum Hamburg-Eppendorf | |
Hamburg, Germany, 20249 | |
Universitätsklinikum Köln (AoeR) | |
Köln, Germany, 50937 | |
Universitätsmedizin der Johannes Gutenberg - Universität Mainz | |
Mainz, Germany, 55131 | |
Portugal | |
Instituto Portugues de Oncologia do Porto Francisco Gentil | |
Porto, Portugal, 4200-072 | |
Spain | |
Hospital Universitario Virgen del Rocio | |
Sevilla, Spain, 41013 |
Study Director: | Adelmann | VectivBio AG |
Responsible Party: | VectivBio AG |
ClinicalTrials.gov Identifier: | NCT05415410 |
Other Study ID Numbers: |
TA799-101 |
First Posted: | June 13, 2022 Key Record Dates |
Last Update Posted: | January 9, 2024 |
Last Verified: | January 2024 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Graft versus host disease GVHD GVHD, Acute |
Steroid-refractory aGVHD Gastrointestinal-GVHD GI-GVHD |
Graft vs Host Disease Immune System Diseases |