Proof-of-concept Trial of Apraglutide in GVHD

GVHD Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05415410
• Other study ID #: TA799-101
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 25, 2022
• Est. completion date: August 30, 2025

Study information

• Verified date: January 2024
• Source: VectivBio AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: August 30, 2025
• Est. primary completion date: August 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Graft vs Host Disease
• GVHD

Intervention

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.

Locations

Country	Name	City	State
Germany	Universitaetsklinikum Duesseldorf	Düsseldorf
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Martin Luther Universität Halle-Wittenberg	Halle
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Köln (AoeR)	Köln
Germany	Universitätsmedizin der Johannes Gutenberg - Universität Mainz	Mainz
Portugal	Instituto Portugues de Oncologia do Porto Francisco Gentil	Porto
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United States	South Austin Medical Center	Austin	Texas
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Ohio State University	Columbus	Ohio
United States	University of Iowa	Iowa City	Iowa
United States	Stanford Cancer Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
VectivBio AG

Countries where clinical trial is conducted

United States,  Germany,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events (AE)	System organ class, frequency and severity	From baseline to week 104
Primary	Occurrence of clinically relevant changes in vital signs	Systolic and diastolic blood pressure in mmHg	From baseline to week 104
Primary	Occurrence of clinically relevant changes in vital signs	Heart rate in Beats per Minute (BPM)	From baseline to week 104
Primary	Occurrence of clinically relevant changes in electrocardiogram	ECG QT Interval	From baseline to week 104
Primary	Occurrence of clinically relevant changes in electrocardiogram	ECG PR interval	From baseline to week 104
Primary	Occurrence of clinically relevant changes in electrocardiogram	ECG QRS interval	From baseline to week 104
Primary	Occurrence of clinically relevant changes in electrocardiogram	ECG rhythm	From baseline to week 104
Primary	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	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
Secondary	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
Secondary	Graft failure post-first dose of apraglutide	Incidence of graft failure	Baseline to 2 years
Secondary	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
Secondary	Overall survival post-first dose of apraglutide		Baseline to 2 years
Secondary	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
Secondary	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
Secondary	Absorption rate constant (ka) of apraglutide through population PK data analysis		Day 7 to day 56
Secondary	Apparent clearance (CL/F) of apraglutide through population PK data analysis		Day 7 to day 56
Secondary	Apparent volume of distribution (Vz/F) of apraglutide through population PK data analysis		Day 7 to day 56