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Study of ALPN-101 in Steroid-resistant or Steroid-refractory Acute GVHD Versus Host Disease (Balance)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04227938
Recruitment Status : Recruiting
First Posted : January 14, 2020
Last Update Posted : May 18, 2020
Sponsor:
Information provided by (Responsible Party):
Alpine Immune Sciences, Inc.

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
Graft Vs Host Disease Drug: ALPN-101 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 97 participants
Allocation: N/A
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Study of ALPN-101 in Steroid-resistant or Steroid-refractory Acute Graft Versus Host Disease (aGVHD)
Actual Study Start Date : May 11, 2020
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : July 2022


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.




Primary Outcome Measures :
  1. Adverse events [ Time Frame: 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 :
  1. Objective Response Rate (ORR) [ Time Frame: From study Day 1 (dosing of ALPN-101) until the date of best response, assessed up to 36 months ]
    Assessed by MAGIC criteria

  2. Duration of Response (DOR) [ Time Frame: From the date of best response until disease progression, assessed up to 36 months ]
  3. Failure-free survival (FFS) [ Time Frame: From study Day 1 (dosing of ALPN-101) until relapse, initiation of new systemic therapy, or non-relapse mortality; assessed up to 36 months ]
  4. Event-free survival (EFS) [ Time Frame: From study Day 1 (dosing of ALPN-101) until disease (aGVHD)-related event or death due to any cause, assessed up to 36 months ]
  5. Non-relapse mortality (NRM) [ Time Frame: From study Day 1 (dosing of ALPN-101) until progression or death due to any cause without prior progression, assessed up to 36 months ]
  6. Malignancy relapse/progression (MR) [ Time Frame: From study Day 1 (dosing of ALPN-101) until the date of relapse/progression of the primary malignancy, assessed up to 36 months ]
  7. Overall survival (OS) [ Time Frame: From study Day 1 (dosing of ALPN-101) until death due to any cause, assessed up to 36 months ]
  8. Time to maximum observed concentration (tmax) of ALPN-101 [ Time Frame: From study Day 1 (dosing of ALPN-101) until Day 29 ]
  9. Maximum observed concentration (Cmax) of ALPN-101 [ Time Frame: From study Day 1 (dosing of ALPN-101) until Day 29 ]
  10. Area under the concentration-time curve (AUC) of ALPN-101 [ Time Frame: From study Day 1 (dosing of ALPN-101) until Day 29 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04227938


Contacts
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Contact: Jan Hillson, MD 206-788-4545 jan.hillson@alpineimmunesciences.com

Locations
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United States, California
City of Hope Medical Center Not yet recruiting
Duarte, California, United States, 91010
Contact: Kay Chanea    626-218-2340    kchanea@coh.org   
Principal Investigator: Amandeep Salhotra, MD         
United States, Colorado
Colorado Blood Cancer Institute Not yet recruiting
Denver, Colorado, United States, 80218
Contact: Alireza Eghtedar, M.D.    720-754-4800    asksarah@sarahcannon.com   
Principal Investigator: Alireza Eghtedar, M.D.         
United States, Florida
University of Miami - Sylvester Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Kirenia Correa    305-243-9590    k.correa@med.miami.edu   
Principal Investigator: Trent Wang, DO         
United States, Kansas
The University of Kansas Hospital Recruiting
Kansas City, Kansas, United States, 66160
Contact: Marc Morrison    913-558-7585    mmorrison3@kumc.edu   
Principal Investigator: Sunil Abhyankar, MD         
United States, Tennessee
Sarah Cannon Center for Blood Cancer Recruiting
Nashville, Tennessee, United States, 37203
Contact: Heather Johnson    615-329-7662    heather.johnson@sarahcannon.com   
Principal Investigator: Jeremy Pantin, MD, FACP         
United States, Texas
St. David's South Austin Medical Center Recruiting
Austin, Texas, United States, 78704
Contact: Rob Gordon    512-816-7399    rob.gordon@sarahcannon.com   
Contact: Renee Stajanovic    512 816 6423    renne.stajanovic@sarahcannon.com   
Principal Investigator: Aravind Ramakrishnan, MD         
Sponsors and Collaborators
Alpine Immune Sciences, Inc.
Investigators
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Study Director: Jan Hillson, MD Alpine Immune Sciences, Inc.

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Responsible Party: Alpine Immune Sciences, Inc.
ClinicalTrials.gov Identifier: NCT04227938    
Other Study ID Numbers: AIS-A02
First Posted: January 14, 2020    Key Record Dates
Last Update Posted: May 18, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alpine Immune Sciences, Inc.:
steroid-resistant acute graft versus host disease
steroid-refractory acute graft versus host disease
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases