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

• ClinicalTrials.gov Identifier: NCT02406651
• Recruitment Status: Completed
• First Posted: April 2, 2015
• Results First Posted: July 22, 2021
• Last Update Posted: July 22, 2021
• Sponsor: EVIVE Biotechnology
• Collaborator: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): EVIVE Biotechnology

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Graft vs Host Disease	Drug: Recombinant Human Interleukin-22 IgG2-Fc (F-652); Drug: Systemic Corticosteroids	Phase 1; Phase 2

Detailed Description:

This is 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 HSCT and have newly diagnosed grade II-IV lower GI aGVHD. The HSCT may be derived from bone marrow, peripheral blood stem cells, or cord blood. The PK of F-652 in this subject population will be investigated. Subjects may be replaced if subject withdrawal is not related to safety or treatment response.

F-652 will be administered in conjunction with prednisone (or equivalent) at the time of the onset of clinical symptoms consistent with GI and/or liver aGVHD. Prednisone (or equivalent) will be given at a dose of 2 mg/kg/day and tapered as per protocol.

F-652 will be administered intravenously at a rate of 100 mL/hour for one hour once per week for four weeks. A total of 4 doses will be administered at a dose of 45 μg/kg each. Subjects will be followed for safety and efficacy through Day 180, and subject survival status will be collected at Day 365.

In the first stage of the trial, a total of 16 subjects will be enrolled. If six or fewer have a Day 28 treatment response, the trial will close due to a lack of efficacy. If seven or more have a response, an additional 11 subjects will be enrolled into study for a total sample size of 27. During the course of a subject's therapy, dose reduction may occur on an individual basis as per protocol.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IIa Study of Recombinant Human Interleukin-22 IgG2-Fc (F 652) in Combination With Systemic Corticosteroids for the Treatment of Newly Diagnosed Grade II-IV Lower Gastrointestinal Acute Graft-versus-Host Disease (aGVHD) in Hematopoietic Stem Cell Transplantation Recipients (HSCT)
• Actual Study Start Date: May 12, 2016
• Actual Primary Completion Date: April 9, 2019
• Actual Study Completion Date: March 8, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: F-652 and systemic coritcosteroids; 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); IV infusion of reconstitution lyophilized F-652.; Other Name: IL-22; Drug: Systemic Corticosteroids; 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.

Outcome Measures

Primary Outcome Measures :

1. The Number of Participants With Lower Gastrointestinal Acute Graft-Versus-Host-Disease Treatment Response Rate on Day 28 [ Time Frame: 28 days after first treatment of F-652 ]
   The number of participants with lower Gastrointestinal Acute Graft-Versus-Host-Disease treatment response rate on Day 28.

Secondary Outcome Measures :

1. The Number of Participants With Lower GI aGVHD Treatment Response at Days 14 and 56. [ Time Frame: Measured at day 14 and 56 after initial dosing of F-652 ]
   The number of participants with Lower GI aGVHD treatment response at days 14 and 56 categorized by complete response (CR), very good partial response (VGPR), partial response (PR), no response (NR)/stable, and progression
2. The Number of Participants With Overall aGVHD Treatment Response at Days 14, 28, and 56. [ Time Frame: Measured at day 14, 28 and 56 after initial dosing of F-652 ]
   The number of participants with overall aGVHD treatment response at Days 14, 28, and 56 categorized by complete response (CR), partial response (PR), no response (NR), and progression.
3. The Number of Participants With Discontinuation of Immunosuppressive Medication at Day 180 and 1 Year Post Initial Dosing of F-652. [ Time Frame: Measured at Day 180 and 1 year after initial dosing of F-652. ]
   The number of participants with discontinuation of immunosuppressive medication at day 180 and one year post initial dose.
4. The Number of Participants With Overall Survival at 1 Year After First Infusion of F-652. [ Time Frame: Measured 1 year after first infusion. ]
   The number of participants with overall survival at 1 year after first infusion of F-652.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥18 years and ≤80.
2. 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.
3. 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.
4. Female subjects of childbearing potential who agree to practice 2 effective methods of contraception.
5. Male subjects, even if surgically sterilized (i.e. Status post-vasectomy) must agree to agree to practice contraception.
6. Have adequate renal function (Serum creatinine <3 mg/dL).
7. ANC >500/mm3.
8. 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.

Exclusion Criteria:

Subjects who met any of the following criteria were excluded from the study:

1. Evidence of relapse or progression of hematologic malignancy at the time of study enrollment.
2. Active uncontrolled infection. Subjects with a controlled infection receiving definitive therapy for 48 hours prior to enrollment were eligible.
3. Subjects requiring vasopressors or mechanical ventilation.
4. 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.
5. 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.
6. Subjects who developed aGVHD after unplanned donor lymphocyte infusion.
7. Subjects with chronic GVHD features (i.e., acute/chronic GVHD overlap syndrome or classical chronic GVHD).
8. History of psoriasis.
9. History of epithelial malignancies including melanoma or any carcinomas.
10. History or diagnosis of mantle cell lymphoma or anaplastic large cell lymphoma.
11. Subject was pregnant or breast-feeding.
12. 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.
13. 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.
14. The subject had tested positive for the Clostridium difficile (C. difficile) toxin within 7 days of study entry.
15. Cytotoxic, biologic, or investigational agents were not permitted throughout the study. These included, but were not limited to, ATG, alemtuzumab, rituximab, photopheresis, and thalidomide. Subjects who participated in any other investigational drug trial or had exposure to any other investigational agent, device, or procedure, within 4 weeks prior to screening and throughout the entire trial, except for trials of investigational drugs administered prophylactically for GVHD or CMV post-allogeneic HSCT. In this exception, the other investigational drug must have been discontinued upon enrolling (i.e., screening/sign ICF) into this study.
16. Any serious medical or psychiatric illness that could, in the Investigator's opinion, potentially have interfered with the completion of treatment according to this protocol.

Contacts and Locations

Locations

United States, California

City of Hope

Duarte, California, United States, 91010

United States, New York

MSKCC

New York, New York, United States, 10065

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

EVIVE Biotechnology

Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Doris Ponce, M.D.; MSKCC

  Study Documents (Full-Text)

Documents provided by EVIVE Biotechnology:

Study Protocol  [PDF] May 30, 2017

Statistical Analysis Plan  [PDF] March 19, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: EVIVE Biotechnology
• ClinicalTrials.gov Identifier: NCT02406651
• Other Study ID Numbers: GC-652-02
• First Posted: April 2, 2015
• Results First Posted: July 22, 2021
• Last Update Posted: July 22, 2021
• Last Verified: July 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Graft vs Host Disease; Immune System Diseases