ALPN-101 in Steroid-resistant or Steroid-refractory Acute GVHD

Study Overview
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Brief Summary
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The Balance study will assess the safety, tolerability, and efficacy of an investigational drug called ALPN-101 in adults with steroid-resistant or steroid-refractory acute graft versus host disease (aGVHD).

Detailed Description
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AIS-A02 is a Phase 1b open-label study of ALPN-101 administered to adult subjects with steroid-resistant or steroid-refractory acute graft versus host disease (aGVHD). It will be conducted at approximately 10 US sites. Up to 72 subjects will be enrolled in Part A (dose escalation) and up to 25 subjects will be enrolled in Part B (dose expansion). In each Part, safety and efficacy assessments will be performed throughout the dosing and follow-up periods, and multiple PK and PD samples will be collected.

Official Title
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An Open-label Study of ALPN-101 in Steroid-resistant or Steroid-refractory Acute Graft Versus Host Disease (aGVHD)

Conditions
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Graft Vs Host Disease

Intervention / Treatment
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* Drug: ALPN-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Status post first allogeneic stem cell transplantation (allo-SCT) from any donor source using any conditioning regimen. Grade Ⅱ-Ⅳ acute GVHD per Mount Sinai Acute GVHD international Consortium (MAGIC) criteria. Corticosteroid resistant or refractory as defined as any of the following: Progression of aGVHD within 5 days following initiation of treatment with ≥ 2 mg/kg/day of prednisone or equivalent; Failure to improve within 7 days following initiation of treatment with ≥ 2 mg/kg/day of prednisone or equivalent; or Incomplete response (failure to achieve Complete Response) after 28 days of immunosuppressive treatment including steroids (treatment with ≥ 2 mg/kg/day of prednisone or equivalent). Must agree to use appropriate contraception. Female subjects must not be pregnant or breastfeeding. In addition, the following criteria must be met prior to dosing with ALPN-101 on Day 1: Karnofsky performance score ≥ 40. No evidence of an active, uncontrolled bacterial, viral, or fungal infection. Exclusion Criteria: Current veno-occlusive disease, or current treatment with dialysis or mechanical ventilation associated with GVHD. Prior donor lymphocyte infusion (DLI). Receipt of any live vaccine within 4 weeks of ALPN-101 dosing. Presence of any active malignant disease. Corticosteroid therapy at doses > 1 mg/kg/day prednisone or equivalent for indications other than GVHD ≤ 7 days p ALPN-101 dosing. Treatment with any of the following ≤ 2 weeks prior to ALPN-101 dosing: targeted inhibitors of the CD28/CD80/86 pathway (e.g. abatacept, belatacept), targeted inhibitors of the ICOS/ICOSL pathway Initiation of treatment with salvage therapy < 2 days prior to ALPN-101 dosing. Concurrent salvage therapy that is intended to be continued must be at a stable dose for ≥ 2 days prior to ALPN-101 dosing. Treatment for aGVHD with adoptive cell therapy, investigational agents, devices, or procedures ≤ 2 weeks or 5 half-lives-whichever is greater-prior to ALPN-101 dosing, unless approved by the medical monitor and sponsor; prior treatment with mesenchymal stem cells is permitted. Known allergies, hypersensitivity, or intolerance to study drug, excipients, or similar compounds. Any medical complications or conditions that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A single dose of ALPN-101 will be administered via intravenous (IV) infusion. Multiple, ascending dose levels will be evaluated in cohorts of 3-6 subjects in Part A. In Part B, a single dose level-as identified in Part A-is planned.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALPN-101<br>All subjects will receive a single dose of ALPN-101. In Part A, ascending dose levels of ALPN-101 will be evaluated. In Part B, a single dose level of ALPN-101-as identified in Part A-will be evaluated. | Drug: ALPN-101<br>* A single dose of ALPN-101 will be administered via intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | The incidence, severity, and seriousness of AEs, including dose-limiting toxicities, assessed by CTCAE | From study Day 1 (dosing of ALPN-101) until Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Assessed by MAGIC criteria | From study Day 1 (dosing of ALPN-101) until the date of best response, assessed up to 36 months | 
| Duration of Response (DOR) |  | From the date of best response until disease progression, assessed up to 36 months | 
| Failure-free survival (FFS) |  | From study Day 1 (dosing of ALPN-101) until relapse, initiation of new systemic therapy, or non-relapse mortality; assessed up to 36 months | 
| Event-free survival (EFS) |  | From study Day 1 (dosing of ALPN-101) until disease (aGVHD)-related event or death due to any cause, assessed up to 36 months | 
| Non-relapse mortality (NRM) |  | From study Day 1 (dosing of ALPN-101) until progression or death due to any cause without prior progression, assessed up to 36 months | 
| Malignancy relapse/progression (MR) |  | From study Day 1 (dosing of ALPN-101) until the date of relapse/progression of the primary malignancy, assessed up to 36 months | 
| Overall survival (OS) |  | From study Day 1 (dosing of ALPN-101) until death due to any cause, assessed up to 36 months | 
| Time to maximum observed concentration (tmax) of ALPN-101 |  | From study Day 1 (dosing of ALPN-101) until Day 29 | 
| Maximum observed concentration (Cmax) of ALPN-101 |  | From study Day 1 (dosing of ALPN-101) until Day 29 | 
| Area under the concentration-time curve (AUC) of ALPN-101 |  | From study Day 1 (dosing of ALPN-101) until Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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steroid-resistant acute graft versus host disease, steroid-refractory acute graft versus host disease