Graft Vs Host Disease
Conditions
Keywords
steroid-resistant acute graft versus host disease, steroid-refractory acute graft versus host disease
Brief summary
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
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.
Interventions
DRUGALPN-101
A single dose of ALPN-101 will be administered via intravenous infusion.
Sponsors
Alpine Immune Sciences, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years 2. Status post first allogeneic stem cell transplantation (allo-SCT) from any donor source using any conditioning regimen. 3. Grade Ⅱ-Ⅳ acute GVHD per Mount Sinai Acute GVHD international Consortium (MAGIC) criteria. 4. Corticosteroid resistant or refractory as defined as any of the following: 1. Progression of aGVHD within 5 days following initiation of treatment with ≥ 2 mg/kg/day of prednisone or equivalent; 2. Failure to improve within 7 days following initiation of treatment with ≥ 2 mg/kg/day of prednisone or equivalent; or 3. 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). 5. Must agree to use appropriate contraception. 6. 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.
Exclusion criteria
1. Current veno-occlusive disease, or current treatment with dialysis or mechanical ventilation associated with GVHD. 2. Prior donor lymphocyte infusion (DLI). 3. Receipt of any live vaccine within 4 weeks of ALPN-101 dosing. 4. Presence of any active malignant disease. 5. Corticosteroid therapy at doses \> 1 mg/kg/day prednisone or equivalent for indications other than GVHD ≤ 7 days p ALPN-101 dosing. 6. 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 7. 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. 8. 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. 9. Known allergies, hypersensitivity, or intolerance to study drug, excipients, or similar compounds. 10. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | From study Day 1 (dosing of ALPN-101) until Day 29 | The incidence, severity, and seriousness of AEs, including dose-limiting toxicities, assessed by CTCAE |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From study Day 1 (dosing of ALPN-101) until the date of best response, assessed up to 36 months | Assessed by MAGIC criteria |
| 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 | — |
| Duration of Response (DOR) | From the date of best response until disease progression, 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 | — |
| 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 | — |
Countries
United States
Outcome results
None listed