Proof-of-concept Trial of Apraglutide in GVHD

• ClinicalTrials.gov Identifier: NCT05415410
• Recruitment Status: Active, not recruiting
• First Posted: June 13, 2022
• Last Update Posted: January 9, 2024
• Sponsor: VectivBio AG
• Information provided by (Responsible Party): VectivBio AG

Tracking Information

• First Submitted Date: February 8, 2022
• First Posted Date: June 13, 2022
• Last Update Posted Date: January 9, 2024
• Actual Study Start Date: May 25, 2022
• Estimated Primary Completion Date: August 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 8, 2022)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 8, 2022)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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).
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: 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.

Study Arms

• Experimental: Apraglutide Low Dose
  Apraglutide SC injections, once weekly, for subjects with body weight of more than 50.0 kg.
  Intervention: Drug: Apraglutide
• Experimental: Apraglutide High Dose
  Apraglutide SC injections, once weekly, for subjects with body weight of more than 50.0 kg.
  Intervention: Drug: Apraglutide
• Experimental: Apraglutide Standard Dose
  Apraglutide SC injections, once weekly, for subjects with body weight between 40.0 kg to 49.9 kg.
  Intervention: Drug: Apraglutide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 8, 2024): 31
• Original Estimated Enrollment (submitted: June 8, 2022): 34
• Estimated Study Completion Date: August 30, 2025
• Estimated Primary Completion Date: August 30, 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Portugal, Spain, United States
• Removed Location Countries: Italy

Administrative Information

• NCT Number: NCT05415410
• Other Study ID Numbers: TA799-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: VectivBio AG
• Original Responsible Party: Same as current
• Current Study Sponsor: VectivBio AG
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Adelmann; VectivBio AG

• PRS Account: VectivBio AG
• Verification Date: January 2024