Apraglutide for Graft-versus-Host Disease

Recruiting at 22 trial locations

Overseen By Eremeeva

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: VectivBio AG

Must be taking: SS, RUX

Must not be taking: Methotrexate, Mycophenolate, others

Disqualifiers: Organ failures, GI tumors, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests apraglutide, a medication administered as a subcutaneous injection, to evaluate its safety and effectiveness for individuals with steroid refractory gastrointestinal aGVHD. This condition occurs in some patients after a stem cell transplant and does not improve with standard steroid treatments. The trial includes three dosing groups to identify the most effective dose. Participants must have persistent gut problems despite usual steroid treatments and weigh at least 40 kg. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that apraglutide is well-tolerated in patients with a specific gut condition unresponsive to steroids. A recent study found apraglutide safe for use up to 91 days, which was the study's main focus. This suggests the treatment is fairly safe for people, based on current information.

In this trial, researchers are testing apraglutide in different doses: low, standard, and high. Evidence so far does not indicate major safety differences between these doses. However, like any medical treatment, some side effects might occur, but they are usually manageable. Apraglutide has not yet received approval from any health authorities, meaning it is still under testing to ensure its safety and efficacy for this condition. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about apraglutide for treating graft-versus-host disease (GVHD) because it offers a unique approach compared to current options, which often include immunosuppressive therapies like corticosteroids. Unlike these treatments, apraglutide is a GLP-2 receptor agonist, which means it works by stimulating the gut to improve its function and integrity, potentially reducing the inflammation and damage associated with GVHD. Additionally, apraglutide is administered as a convenient once-weekly subcutaneous injection, which could enhance patient adherence and quality of life. This innovative mechanism and delivery method have the potential to offer a more targeted and less immunosuppressive approach to managing GVHD.

What evidence suggests that apraglutide might be an effective treatment for gastrointestinal aGVHD?

Research has shown that apraglutide may help treat steroid-refractory gastrointestinal acute graft-versus-host disease (GI aGVHD). In one study, participants tolerated apraglutide well, and it proved safe to use, which is encouraging for those considering this treatment. This trial will evaluate different doses of apraglutide—low, standard, and high—to determine its effectiveness and safety. Another study found that combining apraglutide with ruxolitinib improved response rates compared to using ruxolitinib alone. This suggests apraglutide might benefit patients who don't respond to steroids. Overall, these findings offer hope that apraglutide could be an effective treatment for this challenging condition. ^{2 4 5 6 7}

Who Is on the Research Team?

Tomasz Masior

Principal Investigator

VectivBio AG

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 and above, weighing at least 40 kg, who have steroid refractory gastrointestinal acute graft versus host disease after a stem cell transplant. Participants must use effective contraception if of childbearing potential and can't be on certain other GVHD therapies or have significant organ failures.

Inclusion Criteria

I am 12 years or older and weigh at least 40 kg.

My lower GI acute graft-versus-host disease hasn't improved with steroids.

I am being treated with SS and RUX, starting them at the same time or RUX up to 72 hours before apraglutide.

Exclusion Criteria

I have GI issues after a treatment to prevent cancer return.

I do not have an active, uncontrolled infection or tuberculosis.

I am not taking any Janus kinase inhibitors except for RUX currently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive apraglutide SC injections once weekly, with doses adjusted based on body weight

26 weeks

Weekly visits for injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

104 weeks

Long-term monitoring

Participants are monitored for graft failure, malignancy relapse, and other outcomes

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Apraglutide

Trial Overview The trial tests the safety and effectiveness of Apraglutide in treating lower GI-aGVHD that hasn’t responded to steroids. Patients will also receive standard treatment with SS plus RUX starting up to five days before or within 72 hours of beginning Apraglutide.

How Is the Trial Designed?

Group I: Apraglutide Standard Dose Experimental Treatment 1 Intervention

Standard-dose apraglutide SC injections (1.4 mg) once weekly for up to 13 weeks (with optional treatment up to an additional 13 weeks), for participants with body weight between 40.0 kg to 49.9 kg.

Group II: Apraglutide Low Dose Experimental Treatment 1 Intervention

Low-dose, weight-based apraglutide subcutaneous (SC) injections (1.4 to 3.5 mg) once weekly for up to 13 weeks (with optional treatment up to an additional 13 weeks), for participants with body weight of more than 50.0 kg.

Group III: Apraglutide High Dose Experimental Treatment 1 Intervention

High-dose, weight-based apraglutide SC injections (3.5 to 7.6 mg) once weekly for up to 13 weeks (with optional treatment up to an additional 13 weeks), for participants with body weight of more than 50.0 kg.

Who Is Running the Clinical Trial?

VectivBio AG

Lead Sponsor

Trials

11

Recruited

490+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/100/530736/Safety-and-Efficacy-of-the-Glucagon-like-Peptide-2

Safety and Efficacy of the Glucagon-like Peptide 2 (GLP-2 ... Twenty-seven (87.1%) pts had grade III-IV aGvHD and 20 (64.5%) pts had lower-GI stage 3-4 aGvHD.

2. investor.ironwoodpharma.com investor.ironwoodpharma.com/press-releases/press-release-details/2024/Ironwood-Pharmaceuticals-Announces-Positive-Results-from-its-Phase-II-Exploratory-STARGAZE-Trial-of-Apraglutide-in-Patients-with-Steroid-Refractory-Gastrointestinal-Acute-Graft-versus-Host-Disease-SR-GI-aGVHD/default.aspx

Press Release Details Results up to Day 91 show that apraglutide in SR GI aGVHD was well-tolerated with an acceptable safety profile, the study's primary objective.

3. onclive.com onclive.com/view/apraglutide-ruxolitinib-provides-efficacy-benefit-vs-ruxolitinib-alone-in-refractory-gi-agvhd

Apraglutide/Ruxolitinib Provides Efficacy Benefit vs ... A comparative analysis showed that apraglutide plus ruxolitinib improved response rates vs ruxolitinib monotherapy in steroid-refractory GI aGVHD.

4. gvhdhub.com gvhdhub.com/medical-information/apraglutide-for-sr-agvhd-results-from-the-phase-ii-stargaze-trial

Results from the phase II STARGAZE trial Learning objective: After reading this article, learners will be able to cite a new clinical development in acute graft-versus-host disease.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12151853/

Teduglutide for treatment-refractory severe intestinal acute ... Figure 1f shows estimated OS rates after one year of 57.1% (95% confidence interval, CI 27.7–78.3%), after two years 47.6% (95% CI 19.5–71.4%).

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124028477

Safety and Efficacy of the Glucagon-like Peptide 2 (GLP-2) ... Apraglutide is an investigational product and has not been approved by any regulatory authority. Introduction:Acute graft-versus-host disease (aGvHD) is a ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05415410

NCT05415410 | Proof-of-concept Trial of Apraglutide in ... The aim of this trial is to assess safety and efficacy of apraglutide in subjects with steroid refractory gastrointestinal acute graft versus host disease ( ...