Acute graft versus host disease (GVHD) MedDRA version: 20.0 Level: PT Classification code 10075160 Term: Graft versus host disease in gastrointestinal tract System Organ Class: 10021428 - Immune system disorders MedDRA version: 20.0 Level: LLT Classification code 10075161 Term: Graft versus host disease in GI tract System Organ Class: 10021428 - Immune system disorders MedDRA version: 20.1 Level: PT Classification code 10066264 Term: Acute graft versus host disease in intestine System Organ C
Conditions
Interventions
Sponsors
VectivBio AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent for this trial prior to any trial specific assessment. A signed assent form will also be required for any subjects under the age of 18 years 2. Male or female subjects aged 12 years or above at the time of consent and who weigh a minimum of 40 kg 3. Have undergone alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible 4. Evident myeloid and platelet engraftment (confirmed prior to trial medication start): a) Absolute neutrophil count >1000/mm3 AND b) Platelets =20,000/mm3 Use of growth factor supplementation (granulocyte-colony stimulating factor and granulocyte-macrophage-colony stimulating factor) and transfusion support is allowed 5. Histologically diagnosed GI-aGVHD at screening (with clinically confirmed SR GI-aGVHD at RUX start and prior to apraglutide start) defined as subjects administered SS, given alone or combined with calcineurin inhibitors (CNI) and either: a) Disease progression based on organ assessment after 3 days OR b) Did not improve after 7 days of treatment with MP 2mg/kg/day equivalent, OR c) Progressed to a new organ after treatment with MP 2 mg/kg/day equivalent for skin and upper GI-aGVHD, OR d) Recurred during or after a steroid taper All subjects must have Stage 1–4 lower GI-aGVHD at enrollment 6. Treated with SS plus RUX (RUX at the recommended dose twice daily for 0–3 days). CNI are allowed as co-medication, if needed 7. Women of childbearing potential must agree to use a highly effective method of contraception during the trial and for 4 weeks after the EOT visit. Such methods include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomized partner. To be considered sterilized or infertile, females must have undergone surgical sterilization (bilateral tubectomy, hysterectomy, or bilateral ovariectomy) or be post-menopausal (defined as at least 12 months amenorrhea without an alternative medical cause, may be confirmed with follicle-stimulating hormone test in case of doubt). Women who do not engage in heterosexual intercourse will be allowed to join the trial without contraception following a thorough discussion with the Investigator to determine if this is feasible for the subject. The following methods are not considered acceptable methods of contraception: calendar, ovulation, symptothermal, post-ovulation methods, withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method 8. Male subjects with a female partner of childbearing potential must commit to practice methods of contraception and abstain from sperm donation during the trial and for 2 weeks after the EOT visit. Nevertheless, if their partners are women of childbearing potential, they must agree to practice contraception and use a highly effective method of contraception during the trial and for 4 weeks after the EOT visit. Such methods include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal
Exclusion criteria
Exclusion criteria: 1. Treatment with any systemic GVHD therapy other than SS and RUX including methotrexate and mycophenolate mofetil. For subjects on GVHD prophylaxis (ciclosporin A, tacrolimus, sirolimus, everolimus, or anti-thymocyte globulin) this medication can be continued 2. Concomitant treatment with Janus kinase inhibitor therapy for any other indication after initiation of current alloSCT conditioning 3. Presence of any systemic corticosteroid therapy for indications other than aGVHD within 7 days prior to screening. Low doses of prednisolone/hydrocortisone for adrenal suppression are allowed 4. Failed alloSCT within the past 6 months before randomization 5. Presence of SR GI-aGVHD occurring after non-scheduled donor lymphocyte infusion administered for pre-emptive treatment of malignancy recurrence 6. Previous administration of any investigational treatment agent within 30 days prior to screening or within five half-lives of the trial medication, whichever is greater. Subjects who have received placebo in a previous study during this period may be included. 7. Known or suspected hypersensitivity to GLP-1 or GLP-2 analogs or apraglutide excipients 8.Any use of enteral glutamine or growth factors such as native GLP-2, GLP-1 or GLP-2 and GLP-1 analogs within 6 months prior to randomization 9.Inability to understand or adhere to the trial visit schedules and other protocol requirements, including subjects not willing to comply due to drug/alcohol abuse or any condition that would interfere with full participation in the trial, including administration of trial medication and attending required trial visits; pose a significant risk to the subject; or interfere with interpretation of trial data 10. Less than 2 weeks anticipated survival at screening 11.Known significant respiratory disease including subjects who are on mechanical ventilation or who have known resting O2 saturation <90% by pulse-oximetry on room air 12.Presence of severely impaired renal function requiring dialysis, or has an estimated creatinine clearance <29 mL/min/1.73m2 measured or calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI; confirmed within 48 hours prior to randomization) 13.Presence of decompensated liver cirrhosis Child-Pugh Class B and C 14.Clinically significant or uncontrolled cardiac disease including acute myocardial infarction within 6 months prior to randomization, uncontrolled hypertension, New York Heart Association Class III or IV congestive heart failure, unstable angina within last 6 months prior to screening, or presence of severe arrhythmia 15.Requirement for vasopressor or inotropic support (within 30 days to randomization) 16.Presence of uncontrolled cholestatic disorders or unresolved sinusoidal obstructive syndrome/veno-occlusive disease of the liver 17.Presence of relapsed primary malignancy, or treatment for relapse after the alloSCT, or requirement for rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse 18.Presence of newly diagnosed malignancies (intestinal- or liver malignancies) or history of chronic gall bladder or bile duct inflammation or biliary obstruction unless cholecystectomy was performed prior to screening 19.Presence of GI tumors or colonic polyps that are not removed 20.Presence of an active uncontrolled infection such as active viral infection (confirmed by peripheral blood viral load) including Epstein Barr virus, SARS-COV-2 virus, human immunodeficiency vir
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): • Gastrointestinal-aGVHD response at Day 56 in subjects with GI-aGVHD treated with apraglutide, SS, and RUX compared with SS and RUX alone (BAT);Timepoint(s) of evaluation of this end point: After day 56 is completed for all subjects;Main Objective: Primary Objective: To assess safety and tolerability of apraglutide in subjects with SR GI-aGVHD of the mid-lower GI tract who are treated with SS and with RUX for 0–3 days Key Efficacy Objective: To evaluate the SR GI-aGVHD response rate at Day 56 in subjects with SR GI-aGVHD Grade II to IV (Mount Sinai aGVHD International Consortium [MAGIC]; Harris 2016) treated with apraglutide, SS, and RUX compared with SS and RUX alone (BAT);Secondary Objective: Key Secondary Objectives: •Evaluate the SR GI-aGVHD response rate at Days 14,28,90,120,150, & 180 in subjects with GI-aGVHD treated with apraglutide and BAT compared with BAT •Estimate overall GVHD response rate at Days 14,28,56,90,120,150, & 180 •Estimate duration of response from Day 56 Secondary Efficacy Objectives: •Assess durability of GI response: -Assess time to complete GI-GVHD response and FFS -Assess individual course of GI-GVHD response and overall GVHD response at Days 14, 28, 56, 90, 120, 150, and 180 -GI-GVHD response in subjects retreated due to GI-GVHD flare up to Day 180 post initial apraglutide dose •Incidence of GI-GVHD flare up to Day 180 following earlier cessation due to complete response •Assess duration of response from Day 29, non relapse mortality, overall survival, individual time courses, doses of BAT up to Day 90 post-initial apraglutide dose and nutrition status •Measure incidence of infections,sepsis,malignancy relapse, secondary malignancies | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Gastrointestinal-aGVHD response at Days 14, 28, 90, 120, 150, and 180 in subjects with GI-aGVHD treated with apraglutide, SS, and RUX compared with SS and RUX alone (BAT). • Overall response at Days 14, 28, 56, 90, 120, 150, and 180 • Duration of response from Day 56;Timepoint(s) of evaluation of this end point: When Days 14, 28, 56, 90, 120, 150, and 180 are completed by all subjects | — |
Countries
Belgium, Germany, Portugal, Spain, United States
Contacts
Public ContactClinical Trial Information Desk
VectivBio AG
Outcome results
None listed