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

• ClinicalTrials.gov Identifier: NCT02406651
• Recruitment Status: Unknown
• First Posted: April 2, 2015
• Last Update Posted: February 5, 2020
• Sponsor: Generon (Shanghai) Corporation Ltd.
• Collaborator: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): Generon (Shanghai) Corporation Ltd.

Tracking Information

• First Submitted Date: March 19, 2015
• First Posted Date: April 2, 2015
• Last Update Posted Date: February 5, 2020
• Actual Study Start Date: May 12, 2016
• Actual Primary Completion Date: April 9, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 1, 2017)

• Number of Adverse events of F-652 in lower GI aGVHD subjects [ Time Frame: 28 days after first treatment of F-652 ]
  Determined by the number of AEs reported
• Number of subjects in treatment response for subjects with lower GI aGVHD [ Time Frame: Day 28 after first treatment of F-652 ]
  assessment of lower GI GVHD response rate to treatment of subjects with F-652

Original Primary Outcome Measures (submitted: March 30, 2015)

• Number of Adverse events of F-652 in lower GI aGVHD subjects [ Time Frame: 28 days after first treatment of F-652 ]
  Determined by the number of AEs reported
• Number of subjects in treatment response for subjects with lower GI aGVHD [ Time Frame: Day 28 after first treatment of F-652 ]
  assessment of lower GI GVHD response rate to treatment of subjects with F-652
• AUC measurements of F-652 in subjects with lower GI aGVHD [ Time Frame: On Dosing day 21. ]
  AUC evaluation in this subject population
• Cmax measurements of F-652 in subjects with lower GI aGVHD [ Time Frame: On Dosing day 2. ]
  Cmax evaluation in this subject population

Current Secondary Outcome Measures (submitted: May 1, 2017)

• Lower GI aGVHD response [ Time Frame: Measured at day 14 and 56 after initial dosing of F-652 ]
  Categorized by complete response (CR), partial response (PR), no response (NR), and progression.
• Overall GVHD response [ Time Frame: Measured at day 14, 28 and 56 after initial dosing of F-652 ]
  Categorized by complete response (CR), partial response (PR), no response (NR), and progression.
• Discontinuation of immunosuppressive medication [ Time Frame: Measured at Day 180 and 1 year after initial dosing of F-652. ]
  Number of days and subject with discontinuation of immunosuppressive medication
• Overall survival of subjects [ Time Frame: Measured 1 year after first infusion. ]
  Number of subjects with survival after 365 days of initial treatment dosing.

Original Secondary Outcome Measures (submitted: March 30, 2015)

• Lower GI aGVHD response [ Time Frame: Measured at day 28 ]
  Categorized by complete response (CR), partial response (PR), no response (NR), and progression.
• Overall GVHD response [ Time Frame: Measured at day 28 ]
  Categorized by complete response (CR), partial response (PR), no response (NR), and progression.
• Discontinuation of immunosuppressive medication [ Time Frame: Measured at Day 180 after initial dosing of F-652. ]
• Overall survival of subjects [ Time Frame: Measured 1 year after first infusion. ]
  Number of subjects with survival after 365 days of initial treatment dosing.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Graft vs Host Disease

Intervention

• 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.

Study Arms

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.

Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: March 30, 2015): 27
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 8, 2020
• Actual Primary Completion Date: April 9, 2019 (Final data collection date for primary outcome measure)

Eligibility 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:

1. Evidence of relapse or progression of hematologic malignancy at the time of study enrollment.
2. Active uncontrolled infection.
3. Subjects requiring vasopressor or mechanical ventilation.
4. Subjects, who have received previous systemic corticosteroids treatment or poorly absorbable corticosteroids for the treatment of aGVHD, for longer than 3 days (72 hours).
5. Subjects who received any corticosteroid therapy (for non-GVHD) at doses >0.5 mg/kg/day prednisone (or equivalent) within 7 days prior to the onset of GVHD therapy.
6. Subjects who developed aGVHD after unplanned donor lymphocyte infusion.
7. Subject with chronic GVHD features (acute/chronic GVHD overlap syndrome or classical chronic GVHD).
8. History of personal psoriasis.
9. History or diagnosis of mantle cell lymphoma or anaplastic large cell lymphoma.
10. Subject is pregnant or breast-feeding.
11. 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.
12. The subject or guardian is unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests.
13. The subject has tested positive for the Clostridium difficile toxin within 7 days of study entry.
14. Receiving other investigational drugs or biologics within 1 month or five half-lives. Cytotoxic or biologic are not permitted throughout the study.
15. ALT (alanine aminotransferase; SGPT), AST (aspartate aminotransferase; SGPT), alkaline phosphatase (ALP) >2.5 upper limit of normal (ULN), unless attributed to GVHD.
16. Chronic active Hepatitis B or C.
17. Subjects with a history of tuberculosis or a history of a chest X-ray suspicious for tuberculosis, unless confirmed to be purified protein derivative (PPD) negative or latent tuberculosis that has been previously treated.
18. Any serious medical or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02406651
• Other Study ID Numbers: GC-652-02
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: Generon (Shanghai) Corporation Ltd.
• Study Sponsor: Generon (Shanghai) Corporation Ltd.
• Collaborators: Memorial Sloan Kettering Cancer Center

Investigators

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

• PRS Account: Generon (Shanghai) Corporation Ltd.
• Verification Date: February 2019