INCA34176-254: A Phase 2, Open-Label, Randomized, Multicenter Study to Evaluate the Safety and Efficacy of Axatilimab in Combination With Ruxolitinib in Participants With Newly Diagnosed Chronic Graft-Versus-Host Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Corp.

Participant type

Pediatric, Patients

Age range

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

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

22 Oct 2024 → ongoing

Decision date (initial)

2024-09-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

INCYTE

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

The primary objective is to determine the preliminary efficacy of axatilimab in combination with ruxolitinib and to assess the contribution of axatilimab to the combination treatment effect in participants with cGVHD.

Secondary objectives 3

1. To determine the safety and tolerability of axatilimab in combination with ruxolitinib in participants with cGVHD.
2. To evaluate the clinical benefit of axatilimab in combination with ruxolitinib in participants with cGVHD with respect to secondary endpoints, assessed for each treatment group.
3. To assess the PK of axatilimab in combination with ruxolitinib in participants with cGVHD

Conditions and MedDRA coding

chronic graft-versus-host disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 1. At least 12 years of age at the time of informed consent. Note: Participants aged 12 to ˂ 18 years will not be enrolled in Germany, Italy, and the UK.
2. New-onset moderate or severe cGVHD, as defined by the 2014 NIH Consensus Criteria
3. History of 1 allo-SCT
4. Willingness to avoid pregnancy or fathering children

Exclusion criteria 8

1. Participants who received more than 1 prior allo-SCT. Prior autologous HCT is allowed.
2. 2. Has overlap cGVHD, defined as the presence of features or characteristics of aGVHD with simultaneous diagnostic and/or distinctive features of cGVHD.
3. Prior systemic treatment for cGVHD, including systemic corticosteroids and extracorporeal photopheresis.
4. Received systemic corticosteroids within 2 weeks prior to C1D1, regardless of indication, except for physiological replacement doses of corticosteroids (ie, < 10 mg/day prednisone equivalent) for adrenal insufficiency.
5. Initiated systemic treatment with CNIs or mTOR inhibitors within 2 weeks prior to C1D1.
6. Prior treatment with a JAK inhibitor within 8 weeks before randomization
7. Pregnant or breastfeeding
8. Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response (OR) at 6 months, defined for each treatment group as CR or PR at 6 months in the absence of new systemic therapy for cGVHD. Response assessment will be based on the 2014 NIH Criteria

Secondary endpoints 7

1. Safety and tolerability will be assessed by evaluating the frequency and severity of AEs (including SAEs) and changes in clinical and laboratory assessments.
2. DOR (in responders only)
3. Proportion of participants with ≥ 7-point improvement in mLSS total score.
4. Best overall response in the first 6 months and on study, based on the 2014 NIH Consensus Criteria
5. OR at 12 months, defined as CR or PR at 12 months
6. PK parameters for axatilimab and ruxolitinib
7. • EFS, defined as the time from the date of randomization to the date of addition or initiation of new systemic therapy for cGVHD, death due to any cause, or Day 1 in the case of treatment failure (ie, non-CR or non-PR by Month 6), whichever occurs first.

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Corp.

Sponsor organisation

Incyte Corp.

Address

1801 Augustine Cut Off

City

Wilmington

Postcode

19803-4404

Country

United States

Scientific contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Public contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Third parties 5

Locations

4 EU/EEA countries · 34 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 114 files

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

Application history

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