GVHDPhase 2NCT05415410
Proof-of-concept Trial of Apraglutide in Acute Graft Versus Host Disease (aGVHD)
A Phase 2 study testing Apraglutide in people with GVHD, run by VectivBio AG at 13 sites in 4 countries.
Trial summary
The aim of this trial is to assess safety and efficacy of apraglutide in subjects with steroid refractory gastrointestinal aGVHD. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- GVHD
- What is being tested?
- Apraglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 13 sitesin 4 countries
- Study dates
- 25 May 2022to 17 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 14Show fewer
- 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
Trial locations and contacts
13 sites in 4 countries.
13 sites in 4 countries
Germany6 sites
Universitätsklinikum Köln (AoeR)
Cologne, 50937
Universitaetsklinikum Duesseldorf
Düsseldorf, 40225
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
Martin Luther Universität Halle-Wittenberg
Halle, 06120
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20249
Universitätsmedizin der Johannes Gutenberg - Universität Mainz
Mainz, 55131
United States5 sites
South Austin Medical Center
Austin, Texas, 78704
Massachusetts General Hospital
Boston, Massachusetts, 02114
The Ohio State University
Columbus, Ohio, 43210
University of Iowa
Iowa City, Iowa, 52242
Stanford Cancer Center
Stanford, California, 94305
Portugal1 site
Instituto Portugues de Oncologia do Porto Francisco Gentil
Porto, 4200-072
About this study
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
The aim of this trial is to assess safety and efficacy of apraglutide in subjects with steroid refractory gastrointestinal aGVHD.
Read the 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).
- Conditions
- GVHD
- Being tested
- Apraglutide
- Keywords
- Graft versus host disease, GVHD, GVHD, Acute, Steroid-refractory aGVHD, Gastrointestinal-GVHD, GI-GVHD
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApraglutideDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Apraglutide Low Dose | Experimental | Low-dose, weight-based apraglutide subcutaneous (SC) injections (1.4 to 3.5 mg) once weekly for up to 13 weeks (with optional treatment up to an additional 13 weeks), for participants with body weight of more than 50.0 kg. Receives: Drug: Apraglutide |
| Apraglutide High Dose | Experimental | High-dose, weight-based apraglutide SC injections (3.5 to 7.6 mg) once weekly for up to 13 weeks (with optional treatment up to an additional 13 weeks), for participants with body weight of more than 50.0 kg. Receives: Drug: Apraglutide |
| Apraglutide Standard Dose | Experimental | Standard-dose apraglutide SC injections (1.4 mg) once weekly for up to 13 weeks (with optional treatment up to an additional 13 weeks), for participants with body weight between 40.0 kg to 49.9 kg. Receives: Drug: Apraglutide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs)
AE=any untoward medical occurrence which does not necessarily have a causal relationship with study drug. Serious AE (SAE)=any AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in a neonate/infant born to a mother or father exposed to study drug; is a clinically significant event in the Investigator's judgment. Treatment-emergent AE (TEAE)=AE with a start on or after the first administration of apraglutide (or present prior to the first dose of apraglutide but worsening in severity after starting treatment relative to the pre-treatment state) up to 28 days after the last dose of apraglutide. Pre-treatment AE=occurs after informed consent and before first dose; post-treatment AE=occurs after 28 days from last dose. AE are graded as follows: mild (1), moderate (2), severe (3), life-threatening (4), death (5).
Measured: Screening (up to 12 weeks) through End of Trial (up to 2 years/104 weeks) for a total of up to 116 weeks
Number of Participants With Treatment-Emergent Adverse Events of Special Interest (AESIs)
An AESI (serious or non-serious) is an AE of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring, additional information, and rapid communication by the Investigator to the Sponsor is appropriate. AESIs include:
- Injection site reactions
- Gastrointestinal obstructions
- Gallbladder, biliary, and pancreatic disease
- Fluid overload
- Colorectal polyps
- Newly diagnosed malignancies
- Systemic hypersensitivity
Measured: From first dose of study drug through End of Trial (up to 2 years/104 weeks) for a total of up to 116 weeks
Number of Participants With Clinically Significant Changes From Baseline Over Time in Vital Signs
Systolic Blood Pressure:
- High is defined as >= 160 mmHg AND >=20 mmHg increase from baseline
- Low is defined as <= 90 mmHg AND >=20 mmHg decrease from baseline
Diastolic Blood Pressure:
- High is defined as >= 100 mmHg AND >=15 mmHg increase from baseline
- Low is defined as <= 50 mmHg AND >=15 mmHg decrease from baseline
Heart Rate:
- High is defined as >= 120 bpm AND >= 15 bpm increase from baseline
- Low is defined as <= 50 bpm AND >= 15 bpm decrease from baseline
Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.
Measured: Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial
Number of Participants With Clinically Significant Changes From Baseline Over Time in QT Corrected for Heart Rate Using Fridericia's Formula (QTcF)
Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.
Measured: Baseline, Weeks 26, 52, 104/End of Trial
Number of Participants With Potentially Clinically Significant Values Over Time in Liver Function Tests: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)
Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.
Measured: Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial
Number of Participants With Potentially Clinically Significant Values Over Time in Liver Function Tests: Total Bilirubin
Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.
Measured: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial
Number of Participants With Potentially Clinically Significant Values Over Time in Liver Function Tests: Potential Hy's Law Cases
Potential Hy's Law cases were defined as ALT or AST >= 3 x ULN AND total bilirubin >= 2 x ULN AND alkaline phosphatase (ALP) <= 2 x ULN at the same visit.
Baseline is defined as the last measurement prior to the first dose of apraglutide.
Measured: Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial
Number of Participants With Anti-drug Antibodies (ADAs) Over Time
Measured: Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial
Shift Table From Baseline to Worst Post-Treatment (WPT) Physical Examinations
Measured: Baseline (BL), up to Week 104/End of Treatment
Secondary outcomes (18)
Overall Response Rate at Day 56 on the Lower Gastrointestinal (GI) Tract Mount Sinai aGVHD International Consortium (MAGIC) Stage
Overall response rate at Day 56 on the lower GI tract MAGIC stage is defined as the percentage of participants with complete response (CR) or partial response (PR) on the lower GI tract MAGIC stage at Day 56. Lower GI (Stool Output/Day) MAGIC Stages are 0: <500 mL/day or <3/episodes/day; 1: 500-999 mL/day or 3-4/episodes/day; 2: 1000-1500 mL/day or 5-7/episodes/day; 3: >1500 mL/day or >7/episodes/day; 4: Severe abdominal pain with or without ileus or grossly bloody stool (regardless of volume).
CR: Score of 0 in lower GI tract MAGIC stage that indicates complete resolution of all signs and symptoms of aGVHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGVHD. PR: Improvement of one stage in lower GI tract MAGIC stage without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response, or non-response of aGVHD.
Measured: Day 56
Overall Response Rate Over Time on the Lower GI Tract MAGIC Stage
Overall response rate on the lower GI tract MAGIC stage is defined as the percentage of participants with CR or PR on the lower GI tract MAGIC stage at given time points. Lower GI (Stool Output/Day) MAGIC Stages are 0: <500 mL/day or <3/episodes/day; 1: 500-999 mL/day or 3-4/episodes/day; 2: 1000-1500 mL/day or 5-7/episodes/day; 3: >1500 mL/day or >7/episodes/day; 4: Severe abdominal pain with or without ileus or grossly bloody stool (regardless of volume).
CR: Score of 0 in lower GI tract MAGIC stage that indicates complete resolution of all signs and symptoms of aGVHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGVHD. PR: Improvement of one stage in lower GI tract MAGIC stage without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response, or non-response of aGVHD.
Measured: Days 14, 28, 56, 91, 119, 147, and 182
Overall Response Rate Over Time on the Total MAGIC Stage
Overall response rate on Total MAGIC staging for each of the 4 evaluable organs of skin, lower and upper GI tract, and liver is defined as the percentage of participants with CR or PR on the total MAGIC stage. Staging values range from 0 to 4, with higher number indicating a worse state of disease. (For complete staging criteria, see: Harris AC, et al. Biol Blood Marrow Transplant. 2016;22(1):4-10.)
CR: A score of 0 for the aGVHD grading in all evaluable organs that indicates complete resolution of all signs and symptoms of aGVHD in all 4 evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGVHD. PR: An improvement of one stage in one or more evaluable organs involved with aGVHD signs or symptoms without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response, or non-response of aGVHD.
Measured: Days 14, 28, 56, 91, 119, 147, and 182
Durable Overall Response Rates on the Lower GI and Total MAGIC Score From Day 28 to Day 56
Durable overall response rate on the Lower GI MAGIC Score from Day 28 to Day 56 is defined as the percentage of participants who had a response (either CR responder or PR responder, see Outcome Measure 10 description for details) on the lower GI at Day 28 and remain a CR responder or PR responder on the lower GI at Day 56.
Durable overall response rate from Day 28 to Day 56 on the Total MAGIC Score is defined as the percentage of participants who had a response (either CR responder or PR responder, see Outcome Measure 12 description for details) on the total MAGIC score at Day 28 and remain a CR responder or PR responder on the total MAGIC score at Day 56.
Total MAGIC staging for each of the 4 evaluable organs of skin, lower and upper GI tract, and liver ranges from 0 to 4, with higher number indicating a worse state of disease. (For complete staging criteria, see: Harris AC, et al. Biol Blood Marrow Transplant. 2016;22(1):4-10.)
Measured: Day 28 to Day 56
Duration of Response From Day 56 on the Total MAGIC Score
Duration of response from Day 56 on the total MAGIC score: defined as the interval from the Day 56 response (PR and CR; see definitions descriptions in Outcome Measure 12) to death or new systemic therapy for aGVHD (including an increase in steroids >2 mg/kg/day methylprednisolone [MP] equivalent), whichever occurs first, with at least 182 days of follow-up.
Total MAGIC staging for each of the 4 evaluable organs of skin, lower and upper GI tract, and liver range from 0 to 4, with higher number indicating a worse state of disease. (For complete staging criteria, see: Harris AC, et al. Biol Blood Marrow Transplant. 2016;22(1):4-10.)
Full range dates are censored. Censored = participants alive and without missing overall response assessment, initiation of additional systemic therapy for aGVHD or increase of >2 mg/kg/day MP equivalent in steroids. Subjects are right censored at their last follow-up visit.
Measured: From Day 56 up to 2 years of follow up after the first dose
Duration of Response From Day 28 on the Total MAGIC Score
Duration of response from Day 28 on the total MAGIC score: defined as the interval from the Day 28 response (PR and CR; see definitions descriptions in Outcome Measure 12) to death or new systemic therapy for aGVHD (including an increase in steroids >2 mg/kg/day methylprednisolone [MP] equivalent), whichever occurs first, with at least 182 days of follow-up.
Total MAGIC staging for each of the 4 evaluable organs of skin, lower and upper GI tract, and liver range from 0 to 4, with higher number indicating a worse state of disease. (For complete staging criteria, see: Harris AC, et al. Biol Blood Marrow Transplant. 2016;22(1):4-10.) Full range dates are censored. Censored = participants alive and without missing overall response assessment, initiation of additional systemic therapy for aGVHD or increase of >2 mg/kg/day MP equivalent in steroids. Subjects are right censored at their last follow-up visit.
Measured: From Day 28 up to 2 years of follow up after the first dose
Duration of Lower GI Response Per MAGIC Score
Individual duration of lower GI response (either CR responder or PR responder, see Outcome Measure 10 description for details) counted from the first response to return to baseline or worse.
Duration of lower GI response is defined as the duration from the first date a participant is identified as a Lower GI MAGIC Score CR or PR responder until the next date a subject is Lower GI MAGIC Score stable disease/progressed disease (SD/PD; i.e., return to baseline or worsening), experiences treatment failure, or dies, whichever occurs first.
Measured: Up to Day 147
Duration of Lower GI Response Per MAGIC Score In Retreated Participants
Individual duration of lower GI response (either CR responder or PR responder, see Outcome Measure 10 description for details) counted from the first response to return to baseline or worse in participants that were re-treated with apraglutide because of a lower GI-aGVHD flare, counted from the first response after apraglutide restart to return to baseline or worse.
Duration of lower GI response is defined as the duration from the first date a participant is identified as a Lower GI MAGIC Score CR or PR responder until the next date a subject is Lower GI MAGIC Score stable disease/progressed disease (SD/PD; i.e., return to baseline or worsening), experiences treatment failure, or dies, whichever occurs first.
Measured: Up to Day 147
Time to Partial or Complete Lower GI Response (PR or CR) Per MAGIC Score
Lower GI (Stool Output/Day) MAGIC Stages are 0: <500 mL/day or <3/episodes/day; 1: 500-999 mL/day or 3-4/episodes/day; 2: 1000-1500 mL/day or 5-7/episodes/day; 3: >1500 mL/day or >7/episodes/day; 4: Severe abdominal pain with or without ileus or grossly bloody stool (regardless of volume).
CR: Score of 0 in lower GI tract MAGIC stage that indicates complete resolution of all signs and symptoms of aGVHD in all evaluable organs without administration of additional systemic therapies for any earlier progression, mixed response or non-response of aGVHD. PR: Improvement of one stage in lower GI tract MAGIC stage without progression in other organs or sites without administration of additional systemic therapies for an earlier progression, mixed response, or non-response of aGVHD.
Measured: From first injection of apraglutide up to Day 57
Best Overall Lower GI Response and Total Response at Any Time Point Up to and Including Day 91
Overall response rate on the Lower GI MAGIC Score is defined as the percentage of participants who had a response (either CR responder or PR responder, see Outcome Measure 10 description for details) on the lower GI score. Overall response rate on the Total MAGIC Score is defined as the percentage of participants who had a response (either CR responder or PR responder, see Outcome Measure 12 description for details) on the total MAGIC score. Best overall lower GI response and total response is defined as overall response (PR or CR) at any time point up to and including Day 91 and before the start of additional systemic therapy for lower GI aGVHD.
MAGIC staging for each of the 4 evaluable organs of skin, lower and upper GI tract, and liver ranges from 0 to 4, with higher number indicating a worse state of disease. (For complete staging criteria, see: Harris AC, et al. Biol Blood Marrow Transplant. 2016;22(1):4-10.)
Measured: From first injection of apraglutide up to Day 91
Failure-Free Survival Post-First Dose of Apraglutide
Failure free survival is defined as time from first dose until death, hematologic malignancy relapse/progression, or treatment failure, whichever comes first. Treatment failure is reported when additional systemic therapies are used for any earlier progression, mixed response or stable aGVHD.
Measured: Baseline up to 2 years
Time to Non-Relapse Mortality up to 2 Years Post Treatment Start
Non-relapse mortality is defined as time from first dose until death without preceding hematologic relapse.
Measured: From first dose of apraglutide up to 2 years
Overall Survival
Overall survival is calculated as the time from first dose of apgraglutide to death.
Measured: Baseline up to 2 years post-first dose of apraglutide
Percentage of Participants With Hematologic Malignancy Relapse/Progression
Measured: Baseline to 2 years
Percentage of Participants With Graft Failure Up to 2 Years Post-first Dose of Apraglutide
Primary graft failure:
Absolute neutrophil count < 0.5 × 10^9/L by Day 28 Hemoglobin <80 g/L and platelets < 20 × 10^9/L Reduced intensity conditioning: Confirmation of donor cell origin is required Cord blood transplant: Up to Day +42
Secondary graft failure:
Absolute neutrophil count < 0.5 × 10^9/L after initial engraftment not related to relapse, infection, or drug toxicity Reduced intensity conditioning: Loss of donor hematopoiesis to < 5%
Measured: From first dose of apraglutide up to 2 years post-first dose
Percentage of Participants Who Experienced Lower-GI Flare by Day 182 After Earlier Cessation of Treatment Due to CR
Incidence of lower GI-aGVHD flare up to Day 182 after the first apraglutide dose following earlier cessation due to complete lower GI-aGVHD response. A lower GI-aGVHD flare is defined as any increase in signs or symptoms of lower GI-aGVHD that is sustained for >24 hours after apraglutide treatment completion following a CR or PR in the lower GI (see Outcome Measure 10 description for details) and requires re-escalation of immunosuppressive therapy (e.g., corticosteroid, calcineurin inhibitors and/or ruxolitinib dosing).
Measured: From first apraglutide dose up to Day 182
Cumulative Ruxolitinib (RUX) and Systemic Steroid (SS) Doses From Start of the RUX Treatment up to Day 91 After the First Dose of Apraglutide
Concomitant treatment with any systemic GVHD therapy other than SS and RUX was prohibited. The exact dose of SS and RUX taken throughout the trial was recorded in the case report form, including any dose adjustments. Systemic steroid dose was computed using the converted systemic methylprednisolone equivalent dose.
Measured: From start of the RUX treatment up to Day 91 after the first dose of apraglutide
Number of Participants With Treatment-Emergent Infections and Sepsis
Measured: From baseline to Day 91 and overall (up to 2 years after the first dose of apraglutide)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2022
- Study start25 May 2022
- Primary completion17 Dec 2024
- Study completion17 Dec 2024
Why it stopped: Company decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GVHDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- VectivBio AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tomasz Masior, Study director, VectivBio AG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05415410
- Sponsor's protocol ID
- TA799-101
- Status last verified
- Oct 2025
- First submitted
- 8 Feb 2022
- Last updated
- 20 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05415410
- Acronym / sponsor ID
- TA799-101
- Conditions
- GVHD
- Keywords
- Graft versus host disease, GVHD, GVHD, Acute, Steroid-refractory aGVHD, Gastrointestinal-GVHD, GI-GVHD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company decision
- Enrolment
- 31 participants (actual)
- Lead sponsor
- VectivBio AGIndustry (pharma, biotech, devices)
- Study start
- 25 May 2022 (actual)
- Primary completion
- 17 Dec 2024 (actual)
- Study completion
- 17 Dec 2024 (actual)
- First posted
- 13 Jun 2022 (actual)
- Results
- Posted 20 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this trial is to assess safety and efficacy of apraglutide in subjects with steroid refractory gastrointestinal 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Apraglutide Low Dose | Experimental | Drug: ApraglutideLow-dose, weight-based apraglutide subcutaneous (SC) injections (1.4 to 3.5 mg) once weekly for up to 13 weeks (with optional treatment up to an additional 13 weeks), for participants with body weight of more than 50.0 kg. |
| Apraglutide High Dose | Experimental | Drug: ApraglutideHigh-dose, weight-based apraglutide SC injections (3.5 to 7.6 mg) once weekly for up to 13 weeks (with optional treatment up to an additional 13 weeks), for participants with body weight of more than 50.0 kg. |
| Apraglutide Standard Dose | Experimental | Drug: ApraglutideStandard-dose apraglutide SC injections (1.4 mg) once weekly for up to 13 weeks (with optional treatment up to an additional 13 weeks), for participants with body weight between 40.0 kg to 49.9 kg. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApraglutideApraglutide 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. | Drug | Apraglutide High Dose, Apraglutide Low Dose, Apraglutide Standard Dose |
Primary outcome
Number of Participants With Adverse Events (AEs)
Time frame: Screening (up to 12 weeks) through End of Trial (up to 2 years/104 weeks) for a total of up to 116 weeks
AE=any untoward medical occurrence which does not necessarily have a causal relationship with study drug. Serious AE (SAE)=any AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in a neonate/infant born to a mother or father exposed to study drug; is a clinically significant event in the Investigator's judgment. Treatment-emergent AE (TEAE)=AE with a start on or after the first administration of apraglutide (or present prior to the first dose of apraglutide but worsening in severity after starting treatment relative to the pre-treatment state) up to 28 days after the last dose of apraglutide. Pre-treatment AE=occurs after informed consent and before first dose; post-treatment AE=occurs after 28 days from last dose. AE are graded as follows: mild (1), moderate (2), severe (3), life-threatening (4), death (5).
Number of Participants With Treatment-Emergent Adverse Events of Special Interest (AESIs)
Time frame: From first dose of study drug through End of Trial (up to 2 years/104 weeks) for a total of up to 116 weeks
An AESI (serious or non-serious) is an AE of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring, additional information, and rapid communication by the Investigator to the Sponsor is appropriate. AESIs include: * Injection site reactions * Gastrointestinal obstructions * Gallbladder, biliary, and pancreatic disease * Fluid overload * Colorectal polyps * Newly diagnosed malignancies * Systemic hypersensitivity
Number of Participants With Clinically Significant Changes From Baseline Over Time in Vital Signs
Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial
Systolic Blood Pressure: * High is defined as >= 160 mmHg AND >=20 mmHg increase from baseline * Low is defined as <= 90 mmHg AND >=20 mmHg decrease from baseline Diastolic Blood Pressure: * High is defined as >= 100 mmHg AND >=15 mmHg increase from baseline * Low is defined as <= 50 mmHg AND >=15 mmHg decrease from baseline Heart Rate: * High is defined as >= 120 bpm AND >= 15 bpm increase from baseline * Low is defined as <= 50 bpm AND >= 15 bpm decrease from baseline Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.
Number of Participants With Clinically Significant Changes From Baseline Over Time in QT Corrected for Heart Rate Using Fridericia's Formula (QTcF)
Time frame: Baseline, Weeks 26, 52, 104/End of Trial
Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.
Number of Participants With Potentially Clinically Significant Values Over Time in Liver Function Tests: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)
Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial
Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.
Number of Participants With Potentially Clinically Significant Values Over Time in Liver Function Tests: Total Bilirubin
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial
Baseline is defined as the last measurement prior to the first dose of apraglutide. Minimum post-baseline is defined as the minimum measurement after the first dose of apraglutide. Maximum post-baseline is defined as the maximum measurement after the first dose of apraglutide.
Number of Participants With Potentially Clinically Significant Values Over Time in Liver Function Tests: Potential Hy's Law Cases
Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial
Potential Hy's Law cases were defined as ALT or AST >= 3 x ULN AND total bilirubin >= 2 x ULN AND alkaline phosphatase (ALP) <= 2 x ULN at the same visit. Baseline is defined as the last measurement prior to the first dose of apraglutide.
Number of Participants With Anti-drug Antibodies (ADAs) Over Time
Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 8, 13, 17, 21, 26, 52, End of Treatment (up to Week 25), Week 104/End of Trial
Shift Table From Baseline to Worst Post-Treatment (WPT) Physical Examinations
Time frame: Baseline (BL), up to Week 104/End of Treatment
18 secondary outcomes
Overall Response Rate at Day 56 on the Lower Gastrointestinal (GI) Tract Mount Sinai aGVHD International Consortium (MAGIC) Stage
Time frame: Day 56
Overall Response Rate Over Time on the Lower GI Tract MAGIC Stage
Time frame: Days 14, 28, 56, 91, 119, 147, and 182
Overall Response Rate Over Time on the Total MAGIC Stage
Time frame: Days 14, 28, 56, 91, 119, 147, and 182
Durable Overall Response Rates on the Lower GI and Total MAGIC Score From Day 28 to Day 56
Time frame: Day 28 to Day 56
Duration of Response From Day 56 on the Total MAGIC Score
Time frame: From Day 56 up to 2 years of follow up after the first dose
Duration of Response From Day 28 on the Total MAGIC Score
Time frame: From Day 28 up to 2 years of follow up after the first dose
Duration of Lower GI Response Per MAGIC Score
Time frame: Up to Day 147
Duration of Lower GI Response Per MAGIC Score In Retreated Participants
Time frame: Up to Day 147
Time to Partial or Complete Lower GI Response (PR or CR) Per MAGIC Score
Time frame: From first injection of apraglutide up to Day 57
Best Overall Lower GI Response and Total Response at Any Time Point Up to and Including Day 91
Time frame: From first injection of apraglutide up to Day 91
Failure-Free Survival Post-First Dose of Apraglutide
Time frame: Baseline up to 2 years
Time to Non-Relapse Mortality up to 2 Years Post Treatment Start
Time frame: From first dose of apraglutide up to 2 years
Overall Survival
Time frame: Baseline up to 2 years post-first dose of apraglutide
Percentage of Participants With Hematologic Malignancy Relapse/Progression
Time frame: Baseline to 2 years
Percentage of Participants With Graft Failure Up to 2 Years Post-first Dose of Apraglutide
Time frame: From first dose of apraglutide up to 2 years post-first dose
Percentage of Participants Who Experienced Lower-GI Flare by Day 182 After Earlier Cessation of Treatment Due to CR
Time frame: From first apraglutide dose up to Day 182
Cumulative Ruxolitinib (RUX) and Systemic Steroid (SS) Doses From Start of the RUX Treatment up to Day 91 After the First Dose of Apraglutide
Time frame: From start of the RUX treatment up to Day 91 after the first dose of apraglutide
Number of Participants With Treatment-Emergent Infections and Sepsis
Time frame: From baseline to Day 91 and overall (up to 2 years after the first dose of apraglutide)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tomasz Masior study director
VectivBio AG
13 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apraglutide in people with GVHD, run by VectivBio AG at 13 sites in 4 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 7 inclusion and 14 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: stopped early, as of the sponsor's last update on 20 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Germany, United States, Portugal, Spain. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 20 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Adverse Events (AEs) (time frame: Screening (up to 12 weeks) through End of Trial (up to 2 years/104 weeks) for a total of up to 116 weeks). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Oct 2025.