Study of IL-22 IgG2-Fc (F-652) for Subjects With Grade II-IV Lower GI aGVHD

NCT02406651 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GC-652-02
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

A Phase IIa single arm open-label study to investigate the safety, tolerability, and PK of F-652 in combination with systemic corticosteroids in subjects who have undergone Hematopoietic Stem Cell Transplantation (HSCT) and have newly diagnosed grade II-IV lower GI acute Graft Verses Host Disease (aGVHD). Treatment with F-652 will be once a week for 4 weeks, with post treatment follow up visits on days 28, 56, 180 and 365.

Conditions

Acute Graft vs Host Disease

Outcome Measures

Primary Outcomes (1)

• The Number of Participants With Lower Gastrointestinal Acute Graft-Versus-Host-Disease Treatment Response Rate on Day 28

  The number of participants with lower Gastrointestinal Acute Graft-Versus-Host-Disease treatment response rate on Day 28.

  28 days after first treatment of F-652

Secondary Outcomes (4)

• The Number of Participants With Lower GI aGVHD Treatment Response at Days 14 and 56.

  Measured at day 14 and 56 after initial dosing of F-652

• The Number of Participants With Overall aGVHD Treatment Response at Days 14, 28, and 56.

  Measured at day 14, 28 and 56 after initial dosing of F-652

• The Number of Participants With Discontinuation of Immunosuppressive Medication at Day 180 and 1 Year Post Initial Dosing of F-652.

  Measured at Day 180 and 1 year after initial dosing of F-652.

• The Number of Participants With Overall Survival at 1 Year After First Infusion of F-652.

  Measured 1 year after first infusion.

Study Arms (1)

F-652 and systemic coritcosteroids

EXPERIMENTAL

Subjects will be dosed once a week for four weeks with Recombinant Human Interleukin-22 IgG2-Fc (F-652). Dosing will be concurrent with systemic corticosteroids.

Drug: Recombinant Human Interleukin-22 IgG2-Fc (F-652); Drug: Systemic Corticosteroids

Interventions

Recombinant Human Interleukin-22 IgG2-Fc (F-652) DRUG

IV infusion of reconstitution lyophilized F-652.

Also known as: IL-22

F-652 and systemic coritcosteroids

Systemic Corticosteroids DRUG

Prednisone (or equivalent) at the time of the onset of clinical symptoms consistent with GI and/or liver aGVHD, as per the standard of care. Prednisone (or equivalent) will be given at a dose of 2 mg/kg/day and tapered as needed.

F-652 and systemic coritcosteroids

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years and ≤80.
• Newly diagnosed lower GI grade II-IV aGVHD with clinical diagnosis based on modified Keystone criteria1 following allogeneic HSCT using bone marrow, peripheral blood stem cells, or cord blood. Grading of aGVHD will be based on International Bone Marrow Transplant Registry (IBMTR) criteria.
• Subjects are willing to undergo a biopsy to confirm lower GI aGVHD. Biopsy results are not needed to initiate treatment. However, if aGVHD is not confirmed histologically, treatment with F-652 will be discontinued.
• Female subjects of childbearing potential who agree to practice 2 effective methods of contraception.
• Male subjects, even if surgically sterilized (i.e. Status post-vasectomy) must agree to agree to practice contraception.
• Have adequate renal function (Serum creatinine \<3 mg/dL).
• ANC \>500/mm3.
• Show evidence of a personally signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial.

You may not qualify if:

• Subjects who met any of the following criteria were excluded from the study:
• Evidence of relapse or progression of hematologic malignancy at the time of study enrollment.
• Active uncontrolled infection. Subjects with a controlled infection receiving definitive therapy for 48 hours prior to enrollment were eligible.
• Subjects requiring vasopressors or mechanical ventilation.
• Subjects who had received previous systemic corticosteroids for the treatment of acute GI GVHD for longer than 5 days. Subjects who were treated with systemic corticosteroids for aGVHD for a prior allogeneic HSCT \>12 months ago were eligible.
• Subjects who received any corticosteroid therapy (for non-GVHD) at doses \>0.5 mg/kg/day prednisone (or IV equivalent) within 7 days prior to the onset of GVHD therapy.
• Subjects who developed aGVHD after unplanned donor lymphocyte infusion.
• Subjects with chronic GVHD features (i.e., acute/chronic GVHD overlap syndrome or classical chronic GVHD).
• History of psoriasis.
• History of epithelial malignancies including melanoma or any carcinomas.
• History or diagnosis of mantle cell lymphoma or anaplastic large cell lymphoma.
• Subject was pregnant or breast-feeding.
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
• The subject or guardian was unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and research tests.
• The subject had tested positive for the Clostridium difficile (C. difficile) toxin within 7 days of study entry.

Sponsors & Collaborators

• EVIVE Biotechnology: lead
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

Location

MSKCC

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Ponce DM, Alousi AM, Nakamura R, Slingerland J, Calafiore M, Sandhu KS, Barker JN, Devlin S, Shia J, Giralt S, Perales MA, Moore G, Fatmi S, Soto C, Gomes A, Giardina P, Marcello L, Yan X, Tang T, Dreyer K, Chen J, Daley WL, Peled JU, van den Brink MRM, Hanash AM. A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract. Blood. 2023 Mar 23;141(12):1389-1401. doi: 10.1182/blood.2021015111.

  PMID: 36399701 DERIVED

MeSH Terms

Interventions

eflepedocokin alfa; Interleukin-22

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Christina Tay
• Organization: Generon/Evive Biotech

christina.tay@evivebiotech.com

1-908-540-0816

Study Officials

• Doris Ponce, M.D.

  MSKCC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: March 19, 2015
• First Posted: April 2, 2015
• Study Start: May 12, 2016
• Primary Completion: April 9, 2019
• Study Completion: March 8, 2020
• Last Updated: July 22, 2021
• Results First Posted: July 22, 2021

Record last verified: 2021-07

Locations

US (3)