Phase 1/2 Dose Finding, Safety and Efficacy Study of Ibrutinib in Pediatric Subjects with Chronic Graft Versus Host Disease (cGVHD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

7 Feb 2019 → 9 Oct 2025

Decision date (initial)

2024-04-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-507330-24-00

EudraCT number

2017-004558-41

ClinicalTrials.gov

NCT03790332

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic

Part A - Dose Finding Study
Primary Objective: To determine the recommended pediatric equivalent dose (RPED) (based on PK and, if applicable, pharmacodynamic data) for use in pediatric subjects (age ≥1 to <12 years) with cGVHD as defined by the 2014 NIH Consensus Development Project Criteria.
Part B - Pharmacokinetics and Safety Study
Primary Objective: To assess the PK and safety of ibrutinib in pediatric subjects (age ≥ 1 to < 22 years) with cGVHD.

Secondary objectives 2

1. Part A - Dose Finding Study 1/ To determine the safety of ibrutinib in pediatric subjects with cGVHD 2/ To assess pharmacodynamics (BTK occupancy) of ibrutinib in pediatric subjects with cGVHD 3/ For those subjects continuing therapy after dose escalation (Part A Continuation Cohort), secondary endpoints will be the same as those outlined under
2. Part B below and will include safety and efficacy B/Part B - Pharmacokinetics, Safety, and Efficacy Study 1/ To evaluate the efficacy of ibrutinib treatment at 24 weeks in pediatric subjects with cGVHD using the 2014 NIH Consensus Development Project Criteria 2/ To evaluate the duration of response to ibrutinib treatment in pediatric subjects with cGVHD 3/ To evaluate the overall survival rate in pediatric subjects with cGVHD treated with ibrutinib 4/ To evaluate safety by assessing the potential impact of ibrutinib on late effects (including effects on growth and development and immune reconstitution) in pediatric subjects with GVHD

Conditions and MedDRA coding

Chronic Graft Versus Host Disease (cGVHD)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001397-PIP04-17

Plan to share IPD

Yes

IPD plan description

“Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at the following link http://yoda.yale.edu”

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Part A: Subjects with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy
2. Part B: Subjects with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy, or subjects with new onset moderate or severe cGVHD and in need of systemic immunosuppression. a. Subjects with new onset moderate or severe cGVHD must not have received previous systemic therapy for cGVHD with the exception of corticosteroids received within 72 hours prior to signing the informed consent form. b. Subjects with newly diagnosed cGVHD may be receiving other immunosuppressants for the prophylaxis or treatment of acute GVHD, but if the subject is receiving prednisone for prophylaxis or treatment of acute GVHD it must be at or below 0.5 mg/kg/d at the time of enrollment.
3. History of allogeneic stem cell transplantation
4. Age • Part A: ≥1 to <12 years of age at the time of enrollment • Part B: ≥1 to <22 years of age at the time of enrollment
5. Written informed consent or parental or guardian permission and assent of children capable of understanding the nature of the study, per country specific or site-specific standards.
6. Ability of subject or, if a minor, parent/guardian to understand the purpose and risks of the study and to provide a signed and dated parental permission and authorization to use protected health information (in accordance with national and local subject privacy regulations); willingness of child to provide an assent, if developmentally able to do so.

Exclusion criteria 10

1. Presence of single organ genito-urinary involvement as the only manifestation of cGVHD. Concurrent Conditions
2. Received an investigational agent within 28 days before enrollment.
3. Received donor lymphocyte infusion (DLI) within 56 days before enrollment.
4. Progressive underlying malignant disease or active post-transplant lymphoproliferative disease.
5. Ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonist.
6. History of other malignancy (not including the underlying malignancy that was the indication for transplant), with the following exceptions: • Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to enrollment and felt to be at low risk for recurrence by treating physician • Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease • Adequately treated cervical carcinoma in situ without current evidence of disease
7. History of major surgery within 28 days before enrollment or lack of full recovery from surgery.
8. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
9. Female subject who is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 3 months of the last dose of study drug. Male subject who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug.
10. Unwilling or unable to participate in all required study evaluations and procedures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part A: The primary endpoint is the PK (AUC) to determine the RPED of ibrutinib for use in pediatric subjects (age ≥ 1 to < 12 years) with cGVHD.
2. Part B: The primary endpoint is the PK (AUC) and safety (treatment-emergent AEs and laboratory abnormalities) of ibrutinib in pediatric subjects (age ≥ 1 to < 22 years) with cGVHD.

Secondary endpoints 2

1. Part A: The secondary endpoints are safety, including treatment-emergent AEs, laboratory abnormalities, and other safety endpoints; pharmacodynamics and for those subjects continuing therapy after dose escalation (Part A Continuation Cohort), secondary endpoints will be the same as outlined under Part B below. B/ Part B: The secondary endpoints include cGVHD response rate at 24 weeks; duration of response; overall survival rate; growth and development in pediatric subjects
2. Part B: The secondary endpoints include cGVHD response rate at 24 weeks; duration of response; overall survival rate; growth and development in pediatric subjects

Investigational products

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

Test 4

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 5

Locations

5 EU/EEA countries · 7 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 28 files

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

Application history

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