A Phase 2A Study of ALXN1007 in Participants With Newly Diagnosed Acute Lower Gastrointestinal Graft-Versus-Host Disease
Condition: Acute Graft-Versus-Host Disease; GIGVHD
MeSH terms: Graft vs Host Disease
Intervention: ALXN1007 10 mg/kg once weekly; ALXN1007 20 mg/kg once weekly; ALXN1007 20 mg/kg twice weekly
Intervention description: ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.; ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.; ALXN1007 is a recombinant humanized monoclonal antibody that binds to complement component C5a and its metabolite C5a desArg.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GIGVHD

Summary:

      The objectives of this trial were to evaluate the safety, tolerability,
      pharmacokinetics/pharmacodynamics (PK/PD) and efficacy of intravenous (IV) ALXN1007 in
      participants with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (GI)
      tract.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must be males or females age 18 years or older.

          -  Participants with Stage 1 to 4 (per the Modified Keystone Grading Schema) acute GVHD
             of the lower GI tract, without signs of chronic GVHD, at the time of diagnosis, which
             developed in the first 180 days following allogeneic hematopoietic cell
             transplantation (HCT) using bone marrow, peripheral blood, or cord blood; or after
             preplanned donor lymphocyte infusion.

          -  Participants are willing to undergo or must have had an endoscopy of the upper and/or
             lower GI tract and biopsy to confirm GI GVHD.

          -  Participants must be receiving systemic corticosteroids.

          -  Participants with an absolute neutrophil count (ANC) >500/microliter (μL) at
             Screening.

          -  Participants and spouse/partner who are of childbearing potential must be using high
             effective contraception consisting of 2 forms of birth control (at least 1 of which
             much be barrier method) starting at Screening and continuing through the entire study
             (for at least 3 months after the last dose of ALXN1007 if study treatment is stopped
             early or participant withdraws consent).

          -  Male participants must not donate sperm during the Screening and Treatment periods,
             and for at least 3 months after the last dose of ALXN1007.

               -  Stage of acute GVHD of the lower GI tract will be determined using the Modified
                  Keystone Grading Schema.

        Exclusion Criteria:

          -  Participants with a body weight > 140 kg (for Cohorts dosing 20 mg/kg of ALXN1007 and
             higher only).

          -  Participants with signs and symptoms of chronic GVHD.

          -  Participants with an active uncontrolled infection.

          -  Participants who test positive for Clostridium difficile (C. difficile) at Screening.

          -  Participants with relapsed/persistent malignancy requiring rapid immune suppression
             withdrawal.

          -  Participants who received an unplanned (not part of the original transplant therapy
             plan) donor lymphocyte infusion.

          -  Participants who received previous systemic treatment for acute GVHD, except for a
             maximum of 3 days (72 hours) of 2 mg/kg corticosteroid therapy.

          -  Participants with unresolved veno-occlusive disease of the liver.

          -  Participants with creatinine clearance <40 milliliters (mL)/minute at Screening, as
             calculated by the Cockcroft-Gault formula.

          -  Participants known to be infected with human immunodeficiency virus (HIV), hepatitis
             B, or hepatitis C.

          -  Participants known to have an uncontrolled thyroid disorder.

          -  Participants who are pregnant, breast feeding, or sexually active and unwilling to use
             effective birth control for the duration of the study.

          -  Participants who participated in any other investigational drug trial or had exposure
             to any other investigational agent, device, or procedure <4 weeks prior to Screening
             and throughout the entire trial, with the exception of investigational drugs
             administered prophylactically for cytomegalovirus (CMV) post allogeneic HCT.