Proof-of-concept Trial of Apraglutide in Acute Graft Versus Host Disease (aGVHD)

NCT05415410 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: TA799-101
• Study Type: interventional
• Target: 31
• Locations: 4 countries
• Sites: 13

Brief Summary

The aim of this trial is to assess safety and efficacy of apraglutide in subjects with steroid refractory gastrointestinal aGVHD.

Conditions

GVHD

Keywords

Graft versus host disease; GVHD; GVHD, Acute; Steroid-refractory aGVHD; Gastrointestinal-GVHD; GI-GVHD

Outcome Measures

Primary Outcomes (9)

• 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).

  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

  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.

  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.

  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.

  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.

  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.

  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

  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

  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

  Day 56

• Overall Response Rate Over Time on the Lower GI Tract MAGIC Stage

  Days 14, 28, 56, 91, 119, 147, and 182

• Overall Response Rate Over Time on the Total MAGIC Stage

  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

  Day 28 to Day 56

• Duration of Response From Day 56 on the Total MAGIC Score

  From Day 56 up to 2 years of follow up after the first dose

Study Arms (3)

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.

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.

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.

Drug: Apraglutide

Interventions

Apraglutide DRUG

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.

Apraglutide High Dose; Apraglutide Low Dose; Apraglutide Standard Dose

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• VectivBio AG: lead

Study Sites (13)

Stanford Cancer Center

Stanford, California, 94305, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

South Austin Medical Center

Austin, Texas, 78704, United States

Location

Universitätsklinikum Köln (AoeR)

Cologne, 50937, Germany

Location

Universitaetsklinikum Duesseldorf

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Martin Luther Universität Halle-Wittenberg

Halle, 06120, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20249, Germany

Location

Universitätsmedizin der Johannes Gutenberg - Universität Mainz

Mainz, 55131, Germany

Location

Instituto Portugues de Oncologia do Porto Francisco Gentil

Porto, 4200-072, Portugal

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

apraglutide

Condition Hierarchy (Ancestors)

Immune System Diseases

Limitations and Caveats

The administered doses during the study were lower than protocol specified doses. This difference was due to dilution effects and injection-related volume loss during injection preparation, and were applied consistently across all injections and participants.

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: VectivBio AG

ClinicalTrialEnquiries@ironwoodpharma.com

617.621.7722

Study Officials

• Tomasz Masior

  VectivBio AG

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: June 13, 2022
• Study Start: May 25, 2022
• Primary Completion: December 17, 2024
• Study Completion: December 17, 2024
• Last Updated: October 20, 2025
• Results First Posted: October 20, 2025

Record last verified: 2025-10

Locations

DE (6); ES (1); PT (1); US (5)