Proof-of-concept Trial of Apraglutide in GVHD

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 acute graft versus host disease (aGVHD).

Study Overview

• Status: Active, not recruiting
• Conditions: GVHD
• Intervention / Treatment: Drug: Apraglutide

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 Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eremeeva; Phone Number: +41615513030; Email: clinicaltrials@vectivbio.com

Study Locations

• Germany
  • Düsseldorf, Germany, 40225
    • Universitaetsklinikum Duesseldorf
  • Freiburg, Germany, 79106
    • Universitatsklinikum Freiburg
  • Halle, Germany, 06120
    • Martin Luther Universitat Halle-Wittenberg
  • Hamburg, Germany, 20249
    • Universitätsklinikum Hamburg-Eppendorf
  • Köln, Germany, 50937
    • Universitätsklinikum Köln (AoeR)
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg - Universität Mainz
• Portugal
  • Porto, Portugal, 4200-072
    • Instituto Portugues de Oncologia do Porto Francisco Gentil
• Spain
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocío
• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Texas
    • Austin, Texas, United States, 78704
      • South Austin Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apraglutide Low 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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AE)	System organ class, frequency and severity	From baseline to week 104
Occurrence of clinically relevant changes in vital signs	Systolic and diastolic blood pressure in mmHg	From baseline to week 104
Occurrence of clinically relevant changes in vital signs	Heart rate in Beats per Minute (BPM)	From baseline to week 104
Occurrence of clinically relevant changes in electrocardiogram	ECG QT Interval	From baseline to week 104
Occurrence of clinically relevant changes in electrocardiogram	ECG PR interval	From baseline to week 104
Occurrence of clinically relevant changes in electrocardiogram	ECG QRS interval	From baseline to week 104
Occurrence of clinically relevant changes in electrocardiogram	ECG rhythm	From baseline to week 104
Occurrence and titer anti-drug antibodies (ADA)	Number of subjects with anti-drug antibodies and their respective titers at specific time points.	From baseline to week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lower gastrointestinal-aGVHD response	Gastrointestinal-aGVHD response will be measured as a change of MAGIC stage for lower GI. Unit: Number of stools/day	At Days 14, 28, 56, 91, 119, 147, and 182
Overall response	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	At days 14, 28, 56, 91, 119, 147, and 182
Graft failure post-first dose of apraglutide	Incidence of graft failure	Baseline to 2 years
Failure free survival post-first dose of apraglutide	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	Baseline to 2 years
Overall survival post-first dose of apraglutide		Baseline to 2 years
Malignancy relapse/progression post-first dose of apraglutide	The time from date of randomization to hematologic disease relapse/progression. Unit:days	Baseline to 2 years
Lower Gastrointestinal-GVHD relapse following complete GI response	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.	Baseline to 2 years
Absorption rate constant (ka) of apraglutide through population PK data analysis		Day 7 to day 56
Apparent clearance (CL/F) of apraglutide through population PK data analysis		Day 7 to day 56
Apparent volume of distribution (Vz/F) of apraglutide through population PK data analysis		Day 7 to day 56

Collaborators and Investigators

• Sponsor: VectivBio AG
• Investigators: Study Director: Adelmann, VectivBio AG

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Estimated): August 30, 2025
• Study Completion (Estimated): August 30, 2025

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 13, 2022

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Graft versus host disease; GVHD; GVHD, Acute; Steroid-refractory aGVHD; Gastrointestinal-GVHD; GI-GVHD
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: TA799-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No