Acute Graft vs Host DiseasePhase 1/2NCT02406651

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

A Phase 1/2 study testing Recombinant Human Interleukin-22 IgG2-Fc (F-652) and Systemic Corticosteroids in people with Acute Graft vs Host Disease, run by EVIVE Biotechnology at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Acute Graft vs Host Disease
What is being tested?: Recombinant Human Interleukin-22 IgG2-Fc (F-652) and Systemic Corticosteroids
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 3 sitesUnited States
Study dates: 12 May 2016to 8 Mar 2020
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 17Show fewer

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.
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.
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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

City of Hope
Duarte, California, 91010
MD Anderson Cancer Center
Houston, Texas, 77030
MSKCC
New York, New York, 10065

Other trials in United States

About this study

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)

Read the 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.

Conditions: Acute Graft vs Host Disease
Being tested: Recombinant Human Interleukin-22 IgG2-Fc (F-652), Systemic Corticosteroids

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Recombinant Human Interleukin-22 IgG2-Fc (F-652)Drug
Also called IL-22
IV infusion of reconstitution lyophilized F-652.
Systemic CorticosteroidsDrug
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 groups in NCT02406651
Study group	Role	What they receive
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. Receives: Drug: Recombinant Human Interleukin-22 IgG2-Fc (F-652); Drug: Systemic Corticosteroids

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
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
Measured: 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.
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.
Measured: 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.
The number of participants with discontinuation of immunosuppressive medication at day 180 and one year post initial dose.
Measured: 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.
The number of participants with overall survival at 1 year after first infusion of F-652.
Measured: Measured 1 year after first infusion.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 May 20168 Mar 2020

First posted2 Apr 2015 (estimated)
Study start12 May 2016
Primary completion9 Apr 2019
Study completion8 Mar 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Acute Graft vs Host DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02406651
Sponsor's protocol ID: GC-652-02
Status last verified: Jul 2021
First submitted: 19 Mar 2015
Last updated: 22 Jul 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 36399701

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 22 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT02406651
Acronym / sponsor ID: GC-652-02
Conditions: Acute Graft vs Host Disease
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: EVIVE BiotechnologyIndustry (pharma, biotech, devices)
Collaborators: Memorial Sloan Kettering Cancer Center
Study start: 12 May 2016 (actual)
Primary completion: 9 Apr 2019 (actual)
Study completion: 8 Mar 2020 (actual)
First posted: 2 Apr 2015 (estimated)
Results: Posted 22 Jul 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
F-652 and systemic coritcosteroids	Experimental	Drug: Recombinant Human Interleukin-22 IgG2-Fc (F-652), Drug: Systemic CorticosteroidsSubjects 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.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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.

Key exclusion criteria (17 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Recombinant Human Interleukin-22 IgG2-Fc (F-652)Also: IL-22IV infusion of reconstitution lyophilized F-652.	Drug	F-652 and systemic coritcosteroids
Systemic CorticosteroidsPrednisone (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.	Drug	F-652 and systemic coritcosteroids

Primary outcome

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.

4 secondary outcomes

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 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 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 Overall Survival at 1 Year After First Infusion of F-652.
Time frame: Measured 1 year after first infusion.

Results and safety

Results posted to the registry on 22 Jul 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
F-652 and Systemic Coritcosteroids	30	27

Primary outcome: 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. Count of participants. Unit: Participants

Measure	F-652 and Systemic Coritcosteroids n = 27
Treatment Response	19
No Treatment Response	8

Population analysed: 30 participants were dosed based on initial screening. Then 3 of the 30 participants were removed after receiving one dose because they failed inclusion/exclusion criteria leaving 27 participants to continue in the study. All participants were exposed to study drug.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs/SAEs were assessed from the time of screening until the end of Day 56 and all causality for mortality was assessed up to 1 year.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
F-652 and Systemic Coritcosteroids	10 of 30 (33.3%)	26 of 30 (86.7%)	4 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36399701Ponce 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Doris Ponce, M.D. principal investigator

MSKCC

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02406651, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2021.