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).

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).

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

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.

Gastrointestinal-aGVHD response will be measured as a change of MAGIC stage for lower GI. Unit: Number of stools/day

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

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

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.

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