ALPN-101 in Steroid-resistant or Steroid-refractory Acute GVHD (Balance)

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

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).

Study Overview

• Status: Terminated
• Conditions: Graft Vs Host Disease
• Intervention / Treatment: Drug: ALPN-101

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Center for Blood Cancer
  • Texas
    • Austin, Texas, United States, 78704
      • St. David's South Austin Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alpine Immune Sciences, Inc.
• Investigators: Study Director: Jan Hillson, MD, Alpine Immune Sciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2020
• Primary Completion (Actual): May 21, 2020
• Study Completion (Actual): May 21, 2020

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 10, 2020
• First Posted (Actual): January 14, 2020

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: steroid-resistant acute graft versus host disease; steroid-refractory acute graft versus host disease
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; ALPN-101
• Other Study ID Numbers: AIS-A02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No