Balance: Study of ALPN-101 in Steroid-resistant or Steroid-refractory Acute GVHD Versus Host Disease
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ALPN-101 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
A single dose of ALPN-101 will be administered via intravenous infusion.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Miami | Miami | Florida | United States | 33136 |
| 2 | University of Kansas Hospital | Kansas City | Kansas | United States | 66160 |
| 3 | Sarah Cannon Center for Blood Cancer | Nashville | Tennessee | United States | 37203 |
| 4 | St. David's South Austin medical Center | Austin | Texas | United States | 78704 |
Sponsors and Collaborators
- Alpine Immune Sciences, Inc.
Investigators
- Study Director: Jan Hillson, MD, Alpine Immune Sciences, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AIS-A02