Study of ALPN-101 in Steroid-resistant or Steroid-refractory Acute GVHD Versus Host Disease
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).
- Graft Vs Host Disease
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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:
7. Karnofsky performance score ≥ 40.
8. No evidence of an active, uncontrolled bacterial, viral, or fungal infection.
- 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.
- Phase 1
- Study Type
- Intervention Model
- Single Group Assignment
- Intervention 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.
- Primary Purpose
- None (Open Label)
|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.||
- Alpine Immune Sciences, Inc.
Study ContactJan Hillson, MD
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.