Activity, Safety and Pharmacokinetics in Pediatric Subjects With Moderate and Severe Chronic Graft vs. Host Disease After Allogeneic Stem Cell Transplant

NCT03774082 | Completed Phase 2 Results DMC

• 2 other identifiers: CINC424G122012018-003296-35
• Study Type: interventional
• Target: 46
• Locations: 14 countries
• Sites: 21

Brief Summary

This open-label, single-arm, Phase II multi-center study enrolled 46 participants and investigated the activity, pharmacokinetics and safety of ruxolitinib added to the subject's immunosuppressive regimen among infants, children, and adolescents aged ≥28 days to \<18 years old with either moderate to severe treatment-naive cGvHD or SR-cGvHD. Although 46 participants were enrolled,1 participant (enrolled in the ≥6y to \<12y age group) received study treatment beyond protocol requirements and was excluded from analyses.

Conditions

Graft vs Host Disease

Keywords

GvHD; INC424; pediatric; Chronic Graft versus Host Disease; moderate and severe chronic graft vs. host disease; allogeneic stem cell transplant; ruxolitinib; corticosteroids

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) at Cycle 7 Day 1

  ORR is defined as the percentage of participants demonstrating a complete response (CR) or partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. The response is assessed per National Institute of Health (NIH) consensus criteria and scoring of response was relative to the organ stage at the start of study treatment.

  At Cycle 7 Day 1 (Day 168); Cycle = 28 Days

Secondary Outcomes (11)

• Ruxolitinib Concentrations by Timepoint

  Cycle 1 Day 1: 0.5, 2 and 6 hours post-dose; Pre-dose on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 3 Day 1, Cycle 5 Day 1 and Cycle 7 Day 1; Cycle = 28 Days

• Duration of Response (DOR)

  From baseline up to 39 cycles; Cycle = 28 Days

• Overall Response Rate (ORR) at Cycle 4 Day 1

  At Cycle 4 Day 1 (Day 84); Cycle = 28 Days

• Best Overall Response (BOR)

  Until Cycle 7 Day 1 (Day 168) or the start of additional systemic therapy for cGvHD; Cycle = 28 Days

• Failure Free Survival (FFS)

  From baseline up to 39 cycles; Cycle = 28 Days

Study Arms (1)

INC424 (ruxolitinib)

EXPERIMENTAL

All pediatric participants received ruxolitinib twice a day (BID) in either tablet or oral solution (liquid), depending on the group they were in.

Drug: INC424

Interventions

INC424 DRUG

Ruxolitinib was taken orally based on age groups as follows: Group 1 (\>=12y to \<18y): 10mg bid as tablet Group 2 (\>=6y to \<12y): 5mg bid as tablet or liquid Group 3 (\>=2y to \<6y): 4mg/m2 bid as liquid

Also known as: Ruxolitinib

INC424 (ruxolitinib)

Eligibility Criteria

• Age: 28 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female subjects age ≥28 days and \<18 years at the time of informed consent.
• Subjects who have undergone a successful alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of myeloablative or reduced intensity conditioning are eligible.
• Subjects with diagnosed moderate to severe cGvHD according to NIH 2014 Consensus Criteria prior to Cycle 1 Day 1. Other possible diagnoses for clinical symptoms supporting cGvHD diagnoses must be excluded (e.g., infection, drug side effects, malignancy). Subjects must be either:
• Treatment-naive cGvHD subjects that have not received any prior systemic treatment for cGvHD except for a maximum 72h of prior systemic corticosteroid therapy of methylprednisolone or equivalent after the onset of chronic GvHD. Subjects are allowed to have received prior systemic treatment for cGvHD prophylaxis (as long as the prophylaxis was started prior to the diagnosis of cGvHD).
• OR o Steroid-refractory moderate to severe cGvHD as per institutional criteria, or per physician decision in case institutional criteria are not available, and still receiving systemic corticosteroids for the treatment of cGvHD for a duration of \<18 months prior to Cycle 1 Day 1. In case the corticosteroids were previously interrupted due to response, the duration of \< 18 months applies to the last period of corticosteroid use.

You may not qualify if:

• SR-cGvHD subjects with a prior cGvHD treatment with a JAK1- or a JAK2- or a JAK1/2-inhibitor, except when the subject achieved complete or partial response and has been off JAK inhibitor treatment for at least 4 weeks prior to Cycle Day 1 or up to 5 times the half-life of the prior JAK inhibitor, whichever is longer.
• \* Subjects who initiated systemic calcineurin inhibitors (CNI; cyclosporine or tacrolimus) within 3 weeks prior to start of ruxolitinib on Cycle 1 Day 1. Note: systemic CNI are allowed when initiated \> 3 weeks from start of ruxolitinib.
• Failed prior alloSCT within the past 6 months
• Significant respiratory disease including subjects who are on mechanical ventilation or who have a resting oxygen saturation \< 90% by pulse-oximetry on room-air.
• Impairment of gastrointestinal (GI) function (unrelated to GvHD) or GI disease (unrelated to GvHD) that may significantly alter the absorption of oral ruxolitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection),
• Cholestatic disorders, or unresolved sinusoidal obstructive syndrome/veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to cGvHD and ongoing organ dysfunction)
• Presence of clinically active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
• Known human immunodeficiency virus (HIV) infection.
• Evidence of uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV) based on assessment done by Investigator or delegate.
• Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
• History of bone disorders such as osteogenesis imperfecta, rickets, renal osteodystrophy, osteomyelitis, osteopenia, fibrous dysplasia, osteomalacia etc. prior to the underlying diagnosis which resulted in the alloSCT.
• History of endocrine or kidney related growth retardation prior to the underlying diagnosis which resulted in the alloSCT.
• Evidence of clinically active tuberculosis (clinical diagnosis per local practice)
• Any corticosteroid therapy for indications other than cGvHD at doses \> 1 mg/kg/daymethylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of the screening visit.
• History of progressive multifocal leuko-encephalopathy (PML).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (21)

Novartis Investigative Site

São Paulo, 04039 001, Brazil

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1X8, Canada

Location

Novartis Investigative Site

Prague, 150 06, Czechia

Location

Novartis Investigative Site

Tamil Nadu, Chennai, 600035, India

Location

Novartis Investigative Site

Pune, Maharashtra, 411004, India

Location

Novartis Investigative Site

Bangalore, 560099, India

Location

Novartis Investigative Site

Delhi, 110 085, India

Location

Novartis Investigative Site

Roma, RM, 00165, Italy

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 466 8560, Japan

Location

Novartis Investigative Site

Saitama, 330 8777, Japan

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Bratislava, 833 40, Slovakia

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Zurich, CH - 8032, Switzerland

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Novartis Investigative Site

Bangkok, 10400, Thailand

Location

Novartis Investigative Site

Adana, 1330, Turkey (Türkiye)

Location

Novartis Investigative Site

Antalya, 07000, Turkey (Türkiye)

Location

Novartis Investigative Site

Antalya, 07070, Turkey (Türkiye)

Location

Related Publications (1)

• Locatelli F, Antmen B, Kang HJ, Koh K, Takahashi Y, Kupesiz A, Dias Matos MGA, Chopra Y, Bhat S, Im HJ, Gungor T, Lu MY, Stefanelli T, Rosko C, St Pierre A, Burock K, Smith Y, Sinclair K, Diaz-de-Heredia C. Ruxolitinib in treatment-naive or corticosteroid-refractory paediatric patients with chronic graft-versus-host disease (REACH5): interim analysis of a single-arm, multicentre, phase 2 study. Lancet Haematol. 2024 Aug;11(8):e580-e592. doi: 10.1016/S2352-3026(24)00174-1. Epub 2024 Jul 10.

  PMID: 39002551 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Lymphoma, Follicular

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

novatis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: December 12, 2018
• Study Start: May 20, 2020
• Primary Completion: February 25, 2022
• Study Completion: August 26, 2024
• Last Updated: December 11, 2025
• Results First Posted: April 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); IN (4); RU (1); JP (2); ES (1); IT (1); KR (2); CZ (1); SL (1); BR (1); CH (1); TW (1); TU (3); TH (1)