Clinical trial NCT03763318: A Study to Evaluate the Safety, Tolerability, PK, PD, and Clinical Activity of EQ001 in Subjects With aGVHD
Official title: A Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of EQ001 in Subjects With Newly Diagnosed Acute Graft Versus Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute-graft-versus-host Disease
aGVHD
GVHD
GVHD, Acute
Lead sponsor: Equillium
Sponsor class: INDUSTRY
Collaborators: name: Biocon Limited
First posted: 2018-12-04
Enrollment: 30
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A is an open label 3+3 dose escalation Part B is blinded and randomized 2:1
Primary purpose: TREATMENT

Brief summary: This is a multi-center study to evaluate the safety, tolerability, PK, PD, and clinical activity of EQ001 in subjects with Acute Graft Versus Host Disease (aGVHD).

Detailed description: The study will enroll approximately 100 subjects in two (2) parts:

Part A is an open label study and will enroll approximately 40 evaluable subjects with aGVHD across 4 cohorts. The total number of patients will depend on the number of dose escalations necessary to enable a decision to be made on the recommended dose to take forward into Part B of the study. The planned dose escalation will start with cohort 1, where subjects will receive EQ001 administered intravenously every two weeks for a total of 5 doses.

Part B is a randomized, double-blind, placebo-controlled study and will enroll approximately 60 additional subjects, randomized in a 2:1 ratio to either active treatment EQ001 (40) or placebo (20). Subjects will receive either EQ001 or placebo administered intravenously every two weeks for a total of 5 doses.

Eligibility criteria: Inclusion Criteria:

1. Male or female subject at least 18 years of age for Part A, and at least 12 years of age for Part B.
2. Recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT) using myeloablative or non myeloablative conditioning regimens.
3. Have a clinical diagnosis of acute GVHD requiring systemic immune suppressive therapy.
4. Deemed by the investigator to be likely to comply with the planned procedure as required by the protocol for the duration of the study

Exclusion Criteria:

1. Presence of morphologic relapsed primary malignancy, treatment for relapse after alloHSCT was performed, or requirement for rapid immunosuppressive treatment withdrawal for early malignancy relapse.
2. Evidence of graft failure based on cytopenia(s), and as determined by the investigator.
3. Evidence of post-transplant lymphoproliferative disease.
4. Any prior therapy for acute GVHD, except for alloHSCT prophylaxis regimens or systemically administered corticosteroids.
5. As determined by the investigator, any medical, psychiatric, or other condition or circumstance that is likely to negatively affect: the subject's participation in this clinical study, the subject's safety, or the reliability of the study data.

Primary outcomes:
measure: Number of Treatment Emergent Adverse Events
timeFrame: Study Day 85
measure: Overall Response Rate
timeFrame: Study Day 29
Secondary outcomes:
measure: Time to Maximum EQ001serum Concentration, Tmax
timeFrame: Day 337
measure: Maximum EQ001 Serum Drug Concentration, Cmax
timeFrame: Study Day 337
measure: Minimum EQ001 Serum Drug Concentration, Cmin
timeFrame: Study Day 337
measure: Total EQ001 Exposure Across Time, AUC (From Zero to Infinity)
timeFrame: Study Day 337
measure: Half Life of EQ001, t1/2
timeFrame: Study Day 337
measure: Volume of Distribution of EQ001, Vd
timeFrame: Study Day 337
measure: Clearance, Cl
timeFrame: Study Day 337
measure: Inflammatory Markers
timeFrame: Study Day 337
measure: CD6 Receptor Expression Levels
timeFrame: Study Day 85
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Gainesville
country: United States
facility: University of Florida Health Shands Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami - Miller School of Medicine
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan - C.S. Mott Children's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University and Barnes Jewish Heart & Vascular Center
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Lineberger Comprehensive Cancer Center
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania, Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Nashville
country: United States
facility: TriStar Centennial Medical Center (SCRI)
state: Tennessee
city: Salt Lake City
country: United States
facility: Intermountain Healthcare
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Equillium
name: Joel Rothman
role: STUDY_DIRECTOR
References:
citation: Rambaldi B, Kim HT, Arihara Y, Asano T, Reynolds C, Manter M, Halpern M, Weber A, Koreth J, Cutler C, Gooptu M, Nikiforow S, Ho VT, Antin JH, Romee R, Ampudia J, Ng C, Connelly S, Soiffer RJ, Ritz J. Phenotypic and functional characterization of the CD6-ALCAM T-cell co-stimulatory pathway after allogeneic cell transplantation. Haematologica. 2022 Nov 1;107(11):2617-2629. doi: 10.3324/haematol.2021.280444.