Clinical trial NCT04227938: ALPN-101 in Steroid-resistant or Steroid-refractory Acute GVHD
Official title: An Open-label Study of ALPN-101 in Steroid-resistant or Steroid-refractory Acute Graft Versus Host Disease (aGVHD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Graft Vs Host Disease
Keywords: steroid-resistant acute graft versus host disease
steroid-refractory acute graft versus host disease
Lead sponsor: Alpine Immune Sciences, Inc.
Sponsor class: INDUSTRY
First posted: 2020-01-14
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: From study Day 1 (dosing of ALPN-101) until Day 29
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From study Day 1 (dosing of ALPN-101) until the date of best response, assessed up to 36 months
measure: Duration of Response (DOR)
timeFrame: From the date of best response until disease progression, assessed up to 36 months
measure: Failure-free survival (FFS)
timeFrame: From study Day 1 (dosing of ALPN-101) until relapse, initiation of new systemic therapy, or non-relapse mortality; assessed up to 36 months
measure: Event-free survival (EFS)
timeFrame: From study Day 1 (dosing of ALPN-101) until disease (aGVHD)-related event or death due to any cause, assessed up to 36 months
measure: Non-relapse mortality (NRM)
timeFrame: From study Day 1 (dosing of ALPN-101) until progression or death due to any cause without prior progression, assessed up to 36 months
measure: Malignancy relapse/progression (MR)
timeFrame: From study Day 1 (dosing of ALPN-101) until the date of relapse/progression of the primary malignancy, assessed up to 36 months
measure: Overall survival (OS)
timeFrame: From study Day 1 (dosing of ALPN-101) until death due to any cause, assessed up to 36 months
measure: Time to maximum observed concentration (tmax) of ALPN-101
timeFrame: From study Day 1 (dosing of ALPN-101) until Day 29
measure: Maximum observed concentration (Cmax) of ALPN-101
timeFrame: From study Day 1 (dosing of ALPN-101) until Day 29
measure: Area under the concentration-time curve (AUC) of ALPN-101
timeFrame: From study Day 1 (dosing of ALPN-101) until Day 29
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Nashville
country: United States
facility: Sarah Cannon Center for Blood Cancer
state: Tennessee
city: Austin
country: United States
facility: St. David's South Austin medical Center
state: Texas
Study officials:
affiliation: Alpine Immune Sciences, Inc.
name: Jan Hillson, MD
role: STUDY_DIRECTOR
References: