A Phase 3 Study of Itolizumab in Combination with Corticosteroids for the Initial Treatment of Acute Graft Versus Host Disease (Complication of Bone Marrow Transplants).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Equillium Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

27 Sep 2022 → 12 May 2025

Decision date (initial)

2024-08-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Equillium, Inc.

External identifiers

EU CT number

2024-516064-28-00

EudraCT number

2021-004529-57

WHO UTN

U1111-1308-4015

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacodynamic, Pharmacokinetic, Safety

To assess the efficacy of itolizumab versus placebo as initial therapy for aGVHD in combination with corticosteroids in achieving early disease response.

Secondary objectives 4

1. 1. To evaluate the durability of response to itolizumab versus placebo as initial therapy for aGVHD in combination with corticosteroids.
2. 2. To evaluate systemic corticosteroid use in subjects treated with itolizumab versus placebo.
3. 3. To assess the impact of itolizumab versus placebo on other clinically relevant efficacy measures, including survival outcomes and cGVHD incidence.
4. 4. To evaluate the safety and tolerability of itolizumab versus placebo as initial therapy for aGVHD in combination with corticosteroids.

Conditions and MedDRA coding

Acute Graft Versus Host Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Age ≥12 years and >40 kg at informed consent/assent. Subjects <18 years may only enroll if locally permitted.
2. 2. Has had an initial allogeneic HSCT for any indication using any graft source, donor source, conditioning regimen intensity or prophylaxis. NOTE: 2 allogeneic HSCTs may be allowed if GVHD did not occur after the first HSCT.
3. 3. Has evidence of myeloid engraftment, defined as an absolute neutrophil count ≥500/mm3 (or ≥0.5 × 10exp9/L) achieved and sustained for 3 laboratory values obtained on different days. Laboratory values prior to Screening may be used.
4. 4. Has a clinical diagnosis of aGVHD Grades III-IV or Grade II with LGI involvement based on Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria - at Screening and randomization. Biopsies to confirm aGVHD should be obtained but are not required and should not delay entry into the study.
5. 5. Began initial systemic corticosteroid treatment with ≥ 1mg/kg/day methylprednisolone or equivalent for aGVHD ≤72 hours prior to the start of study drug dosing AND must receive 2 mg/kg/day methylprednisolone or equivalent on Day 1.

Exclusion criteria 8

1. 1. Has evidence of morphological relapsed, progressive, persistent, or untreated malignancy, with the exception of nonmelanoma skin cancer and in situ ductal carcinoma of the breast.
2. 2. Has an unplanned donor lymphocyte infusion for persistent or recurrent malignancy after HSCT.
3. 3. Has evidence of persistent molecular disease requiring treatment (eg, standard chemotherapy or tyrosine kinase inhibitors) that was not specified prior to HSCT.
4. 4. Has evidence of cGVHD or overlap syndrome, as defined by 2014 NIH Consensus Criteria.
5. 5. Is using immunosuppressants other than corticosteroids for the treatment of aGVHD. Continued use of immunosuppressants as GVHD prophylaxis agents is permitted.
6. 6. Has received any systemic corticosteroids of >0.5 mg/kg/day methylprednisolone or equivalent for any indication other than aGVHD within 7 days before the onset of aGVHD. Systemic corticosteroids administered as premedication before blood product transfusions or IV medications to prevent infusion-related reactions are allowed.
7. 7. Has a clinically active, uncontrolled bacterial, viral, or fungal infection, despite adequate treatment. No signs of progression of the infection can be present at randomization. Asymptomatic cytomegalovirus (CMV), Epstein–Barr virus (EBV), or human Herpesvirus 6 (HHV-6) viremia based on viral load or a viral load that is declining with treatment does not constitute a clinically active infection.
8. 8. Other Protocol-defined criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete Response rate at Day 29.

Secondary endpoints 2

1. 1. Overall response rate at Day 29.
2. 2. Durable complete response rate from Day 29 through Day 99.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Equillium Inc.

Sponsor organisation

Equillium Inc.

Address

2223 Avenida De La Playa Suite 108

City

La Jolla

Postcode

92037-3217

Country

United States

Scientific contact point

Organisation

Equillium Inc.

Contact name

Clinical Trials Information

Public contact point

Organisation

Equillium Inc.

Contact name

Clinical Trials Information

Third parties 9

Locations

6 EU/EEA countries · 61 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 87 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications