ALPN-101 in Steroid-resistant or Steroid-refractory Acute GVHD

NCT04227938 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: AIS-A02
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 4

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).

Conditions

Graft Vs Host Disease

Keywords

steroid-resistant acute graft versus host disease; steroid-refractory acute graft versus host disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Objective Response Rate (ORR)

  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

Study Arms (1)

ALPN-101

EXPERIMENTAL

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

Interventions

ALPN-101 DRUG

A single dose of ALPN-101 will be administered via intravenous infusion.

ALPN-101

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alpine Immune Sciences, Inc.: lead

Study Sites (4)

University of Miami

Miami, Florida, 33136, United States

Location

University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

Sarah Cannon Center for Blood Cancer

Nashville, Tennessee, 37203, United States

Location

St. David's South Austin medical Center

Austin, Texas, 78704, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

ALPN-101

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Jan Hillson, MD

  Alpine Immune Sciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 6, 2020
• First Posted: January 14, 2020
• Study Start: May 11, 2020
• Primary Completion: May 21, 2020
• Study Completion: May 21, 2020
• Last Updated: August 28, 2023

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)