Clinical trial NCT05415410: Proof-of-concept Trial of Apraglutide in GVHD
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: GVHD
Keywords: Graft versus host disease
GVHD
GVHD, Acute
Steroid-refractory aGVHD
Gastrointestinal-GVHD
GI-GVHD
Lead sponsor: VectivBio AG
Sponsor class: INDUSTRY
First posted: 2022-06-13
Enrollment: 31
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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).

Eligibility criteria: 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

Primary outcomes:
measure: Adverse events (AE)
timeFrame: From baseline to week 104
measure: Occurrence of clinically relevant changes in vital signs
timeFrame: From baseline to week 104
measure: Occurrence of clinically relevant changes in vital signs
timeFrame: From baseline to week 104
measure: Occurrence of clinically relevant changes in electrocardiogram
timeFrame: From baseline to week 104
measure: Occurrence of clinically relevant changes in electrocardiogram
timeFrame: From baseline to week 104
measure: Occurrence of clinically relevant changes in electrocardiogram
timeFrame: From baseline to week 104
measure: Occurrence of clinically relevant changes in electrocardiogram
timeFrame: From baseline to week 104
measure: Occurrence and titer anti-drug antibodies (ADA)
timeFrame: From baseline to week 104
Secondary outcomes:
measure: Lower gastrointestinal-aGVHD response
timeFrame: At Days 14, 28, 56, 91, 119, 147, and 182
measure: Overall response
timeFrame: At days 14, 28, 56, 91, 119, 147, and 182
measure: Graft failure post-first dose of apraglutide
timeFrame: Baseline to 2 years
measure: Failure free survival post-first dose of apraglutide
timeFrame: Baseline to 2 years
measure: Overall survival post-first dose of apraglutide
timeFrame: Baseline to 2 years
measure: Malignancy relapse/progression post-first dose of apraglutide
timeFrame: Baseline to 2 years
measure: Lower Gastrointestinal-GVHD relapse following complete GI response
timeFrame: Baseline to 2 years
measure: Absorption rate constant (ka) of apraglutide through population PK data analysis
timeFrame: Day 7 to day 56
measure: Apparent clearance (CL/F) of apraglutide through population PK data analysis
timeFrame: Day 7 to day 56
measure: Apparent volume of distribution (Vz/F) of apraglutide through population PK data analysis
timeFrame: Day 7 to day 56
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Austin
country: United States
facility: South Austin Medical Center
state: Texas
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Halle
country: Germany
facility: Martin Luther Universität Halle-Wittenberg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Köln
country: Germany
facility: Universitätsklinikum Köln (AoeR)
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg - Universität Mainz
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: VectivBio AG
name: Holger Adelmann
role: STUDY_DIRECTOR
References: