Phase II Trial of Efprezimod Alfa (CD24Fc, MK-7110) for the Prevention of Acute Graft-Versus-Host Disease (GVHD) Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-002)

NCT02663622 | Completed Phase 2 Results DMC FDA Drug

• 9 other identifiers: 7110-002HUM0010780515-4789R44CA221513R44CA246991UMCC 2015.181MK-7110-002NCI-2017-00017CD24Fc-002
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multicenter prospective phase IIa dose escalation and phase IIa expansion cohort clinical trial designed to evaluate the safety and tolerability of efprezimod alfa for acute GVHD prophylaxis.

Conditions

Graft Versus Host Disease; Hematopoietic Stem Cell Transplantation; Leukemia

Outcome Measures

Primary Outcomes (4)

• Number of Participants Who Experienced an Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented. As described in the protocol, AEs reported after the protocol-specified timeframe were not analyzed in this outcome measure: 1 day prior to hematopoietic stem cell transplantation (HCT) through either 30 or 60 days post-HCT, depending on arm as defined in the Time Frame section.

  Up to approximately 32 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to approximately 62 days for the CD24Fc 960 mg arm.

• Number of Participants Who Discontinued Study Treatment Due to an AE

  An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.

  1 day for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to approximately 30 days for the CD24Fc 960 mg arm.

• Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)

  A DLT was defined as: any Grade III or higher non-hematologic toxicity not clearly related to the underlying malignancy, intercurrent infection, or the hematopoietic stem cell transplantation conditioning regimen; any death not related to relapse or intercurrent infection; and failure to engraft by day 30. Event grading was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 criteria. Hypersensitivity reactions and other infusion-related reactions were not considered DLTs.

  Up to 32 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to 62 days for the CD24Fc 960 mg arm.

• Open Label Expansion Arm Only: Grade III-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS)

  AGFS was defined as the time from the date of hematopoietic stem cell transplantation (HCT) to the earliest of Grade III-IV acute GVHD or death due to any cause, whichever occurred first. Event grading was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 criteria. Participants were censored at 181 days.

  Up to 181 days

Secondary Outcomes (9)

• Grade II-IV Acute Graft-Versus-Host Disease (GVHD) Free Survival (AGFS)

  Up to 195 days for the Placebo, CD24Fc 240 mg, and CD24Fc 480 mg arms. Up to 181 days for the CD24Fc 960 mg arm.

• Percentage of Participants Experiencing Grade II to IV Acute GVHD Following HCT

  Up to approximately 108 days

• Percentage of Participants Experiencing Chronic GVHD Following HCT

  Up to 380 days

• Percentage of Participants Experiencing Relapse Following HCT

  Up to 380 days

• Percentage of Participants Experiencing Non-Relapse Mortality (NRM) Following HCT

  Up to 380 days

Study Arms (4)

Efprezimod alfa 240 mg

EXPERIMENTAL

Efprezimod alfa in 240 mg as intravenous (IV) infusion at Day -1 + Tacrolimus (begin on day -3. IV \[0.03 mg/kg/day\] or PO \[0.045 mg/kg/dose\] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/square meter/dose once daily on Day 1 after HCT, and at a dose of 10 mg/square meter/dose on days 3, 6, and 11 after HCT)

Drug: Efprezimod alfa; Drug: Methotrexate; Drug: Tacrolimus

Efprezimod alfa 480 mg

EXPERIMENTAL

Efprezimod alfa in 480 mg as intravenous (IV) infusion at Day -1 + Tacrolimus (begin on day -3. IV \[0.03 mg/kg/day\] or PO \[0.045 mg/kg/dose\] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/square meter/dose once daily on Day 1 after HCT, and at a dose of 10 mg/square meter/dose on days 3, 6, and 11 after HCT)

Drug: Efprezimod alfa; Drug: Methotrexate; Drug: Tacrolimus

Efprezimod alfa 960 mg

EXPERIMENTAL

Efprezimod alfa (480 mg (day -1), 240 mg (day +14) and 240 mg (day +28)) + Tacrolimus (begin on day -3. IV \[0.03 mg/kg/day\] or PO \[0.045 mg/kg/dose\] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/square meter/dose once daily on Day 1 after HCT, and at a dose of 10 mg/square meter/dose on days 3, 6, and 11 after HCT)

Drug: Efprezimod alfa; Drug: Methotrexate; Drug: Tacrolimus

Placebo

PLACEBO COMPARATOR

Placebo to efprezimod alfa (saline IV injection solution) on day -1 or days -1, 14, and 28 + Tacrolimus (begin on day -3. IV \[0.03 mg/kg/day\] or PO \[0.045 mg/kg/dose\] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/square meter/dose once daily on Day 1 after HCT, and at a dose of 10 mg/square meter/dose on days 3, 6, and 11 after HCT)

Drug: Methotrexate; Drug: Tacrolimus; Drug: Placebo

Interventions

Efprezimod alfa DRUG

Acute GVHD prophylaxis

Also known as: CD24 Fusion Protein, MK-7110

Efprezimod alfa 240 mg; Efprezimod alfa 480 mg; Efprezimod alfa 960 mg

Methotrexate DRUG

Acute GVHD prophylaxis

Also known as: Trexall

Efprezimod alfa 240 mg; Efprezimod alfa 480 mg; Efprezimod alfa 960 mg; Placebo

Tacrolimus DRUG

Acute GVHD prophylaxis

Also known as: FK506, Prograf

Efprezimod alfa 240 mg; Efprezimod alfa 480 mg; Efprezimod alfa 960 mg; Placebo

Placebo DRUG

100 ml saline IV infusion.

Also known as: Saline Solution

Placebo

Eligibility Criteria

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

You may qualify if:

• A prospective participant for allogeneic hematopoietic stem cell transplantation (HCT) for a malignant hematologic disorder.
• The donor and recipient must have a human leukocyte antigen (HLA)-8/8 allelic match at the HLA-A, -B, -C, and - DRB1 loci. High-resolution typing is required for all alleles for unmatched donors. Only matched unrelated donors are acceptable for this trial.
• The following diagnoses are to be included:
• Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) in first or second remission. Remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment, \< 5% blasts in the bone marrow and absence of extramedullary disease including central nervous system (CNS) involvement.
• Chronic Myelogenous Leukemia (CML) in first or subsequent chronic phase failing to respond (or intolerant) to at least two different tyrosine kinase inhibitors. CML in accelerated or blast phase (CML-AP/BP) are eligible without requirement to fail tyrosine kinase inhibitor therapy, but must be in remission at time of enrollment. Remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment, \< 5% blasts in the bone marrow and absence of extramedullary disease including CNS involvement.
• Myelodysplastic syndrome (MDS) with intermediate or high-risk International Prognostic Scoring System (IPSS) or equivalent Revised IPSS (IPSS-R) score with \< 10% blasts in the bone marrow.
• Chronic Myelomonocytic Leukemia (CMML) with \< 10% blasts in the bone marrow.
• Males or non-pregnant, non-lactating females, ≥ 18 years of age. Note there is no defined upper age limited, so long as deemed appropriate candidate for myeloablative conditioning.
• Karnofsky Performance Status \>70%.
• Participants must have normal or near normal organ function as defined by their treating institutions bone marrow transplantation (BMT) program clinical practice guidelines. In addition, for purposes of this protocol minimum organ function criteria within 21 days of beginning conditioning include:
• TABLE 1: Eligibility According to Pre HCT Organ Function Total bilirubin ≤2.5 mg% (unless from Gilbert's disease or disease-related) Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase) (AST\[SGOT\])/ alanine aminotransferase (serum glutamic-pyruvic transaminase) (ALT\[SGPT\]) \<3.0 X institutional upper limit of normal Estimated or actual glomerular filtration rate (GFR) \>50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (GFR should be corrected for body surface area \[BSA\]) Pulmonary Function Tests\* diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) \> 50% DLCO should be corrected for hemoglobin Ejection Fraction\* \>50% Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) ≤ 5
• \*May be assessed up to 6 weeks prior to the start of conditioning therapy
• Ability to understand and the willingness to sign a written informed consent document.
• Women of child bearing potential and men must agree to use contraception prior to study entry and through day 100 post HCT (hormonal or barrier method of birth control; abstinence). Should a woman become pregnant or suspect she is pregnant while she or her partner is on treatment in this study, she should inform her study physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study until day 100 post HCT.

You may not qualify if:

• Participants may not have presence of active CNS disease or extramedullary disease.
• Prior cytotoxic chemotherapy within 21 days from the initiation of HCT conditioning (i.e. intensive induction / consolidation for AML). Note, certain low intensity treatments not intended to induce remission but rather stabilize disease are acceptable up to 24 hrs prior to initiation of HCT conditioning (i.e. Tyrosine Kinase Inhibitor, sorafenib).
• Cord blood and haploidentical donors are not eligible.
• HLA-mismatch at the HLA-A, -B, -C, and - DRB1 loci. Note, HLA-DQ mismatches are permissible.
• Pregnant and nursing mothers are excluded from this study. This is because the risk to the fetus is unknown.
• Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the participant or raise concern that the participant would not comply with protocol procedures.
• Uncontrolled infections. Participants still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiologic, clinical and/or culture) that the infection is well controlled.
• Participants seropositive or polymerase chain reaction (PCR) positive for the human immunodeficiency virus (HIV). Participants with evidence of Hepatitis B or Hepatitis C PCR positivity.
• Prior HCT (allograft or prior autograft).
• Use of T cell depletion either ex vivo or in vivo (i.e. anti-thymocyte globulin \[ATG\], alemtuzumab) is prohibited.
• Current or prior diagnosis of antecedent Myelofibrosis is excluded.

Sponsors & Collaborators

• Oncoimmune, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead
• Ohio State University: collaborator
• University of Michigan Rogel Cancer Center: collaborator
• Indiana University School of Medicine: collaborator
• Barbara Ann Karmanos Cancer Institute: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

The University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (4)

• Toubai T, Rossi C, Oravecz-Wilson K, Zajac C, Liu C, Braun T, Fujiwara H, Wu J, Sun Y, Brabbs S, Tamaki H, Magenau J, Zheng P, Liu Y, Reddy P. Siglec-G represses DAMP-mediated effects on T cells. JCI Insight. 2017 Jul 20;2(14):e92293. doi: 10.1172/jci.insight.92293. eCollection 2017 Jul 20.

  PMID: 28724800 BACKGROUND

• Toubai T, Hou G, Mathewson N, Liu C, Wang Y, Oravecz-Wilson K, Cummings E, Rossi C, Evers R, Sun Y, Wu J, Choi SW, Fang D, Zheng P, Liu Y, Reddy P. Siglec-G-CD24 axis controls the severity of graft-versus-host disease in mice. Blood. 2014 May 29;123(22):3512-23. doi: 10.1182/blood-2013-12-545335. Epub 2014 Apr 2.

  PMID: 24695850 BACKGROUND

• Toubai T, Mathewson ND, Magenau J, Reddy P. Danger Signals and Graft-versus-host Disease: Current Understanding and Future Perspectives. Front Immunol. 2016 Nov 29;7:539. doi: 10.3389/fimmu.2016.00539. eCollection 2016.

  PMID: 27965667 BACKGROUND

• Magenau J, Jaglowski S, Uberti J, Farag SS, Riwes MM, Pawarode A, Anand S, Ghosh M, Maciejewski J, Braun T, Devenport M, Lu S, Banerjee B, DaSilva C, Devine S, Zhang MJ, Burns LJ, Liu Y, Zheng P, Reddy P. A phase 2 trial of CD24Fc for prevention of graft-versus-host disease. Blood. 2024 Jan 4;143(1):21-31. doi: 10.1182/blood.2023020250.

  PMID: 37647633 RESULT

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Graft vs Host Disease; Leukemia

Interventions

Methotrexate; Tacrolimus; Saline Solution

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study was double blind for the first 6 participants in each arm. At that point, the recommended phase II dose (RP2D) was determined, and the selected arm enrolled additional participants in an open label fashion.

Study Record Dates

• First Submitted: January 21, 2016
• First Posted: January 26, 2016
• Study Start: September 19, 2016
• Primary Completion: June 8, 2020
• Study Completion: May 18, 2021
• Last Updated: January 23, 2024
• Results First Posted: June 18, 2021

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

US (4)