Phase 2 Study of Axatilimab at 3 Different Doses in Patients with Chronic Graft Versus Host Disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Syndax Pharmaceuticals 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

19 Jul 2021 → ongoing

Decision date (initial)

2024-07-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Syndax Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-512978-99-00

EudraCT number

2020-005107-40

WHO UTN

U1111-1305-8459

ClinicalTrials.gov

NCT04710576

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacokinetic, Safety, Pharmacodynamic

To evaluate the overall response rate (ORR) of axatilimab at 0.3 mg/kg IV Q2W, 1 mg/kg IV Q2W, and 3 mg/kg IV Q4W in patients with cGVHD after failure of least 2 prior lines of therapy.

Secondary objectives 7

1. 1. To evaluate key secondary measures of clinical benefit.
2. 2. To evaluate secondary measures of clinical benefit.
3. 3. To evaluate the safety and tolerability of axatilimab in patients with cGVHD.
4. 4. To assess the plasma population PK profile of axatilimab in patients with cGVHD.
5. 5. To assess pharmacodynamic profile of axatilimab.
6. 6. To determine or assess the changes in monocyte level with response.
7. 7. To determine or assess the baseline in monocyte level with response.

Conditions and MedDRA coding

Chronic graft versus host disease (cGVHD)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Patient must be 18 years of age or older, at the time of signing the informed consent.
2. 2. Patients who are allogeneic HSCT recipients with active cGVHD requiring systemic immune suppression. Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD
3. 3. Patients with refractory or recurrent active cGVHD despite at least 2 lines of systemic therapy. - Refractory disease is defined as meeting any of the following criteria: -- The development of 1 or more new sites of disease while being treated for cGVHD. -- Progression of existing sites of disease despite at least 1 month of standard or investigation therapy for cGVHD. -- Patients who have not achieved a response within 3 months on their prior therapy for cGVHD and for whom the treating physician believes a new systemic therapy is required. - Recurrent cGVHD is active, symptomatic disease (after an initial response to prior therapy) as defined, based on the NIH 2014 consensus criteria, by organ-specific or global assessment or for which the physician believes that a new line of systemic therapy is required.
4. 4. Patients may have persistent, active acute and cGVHD manifestations (overlap syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
5. 5. Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance Score of ≥60 (if aged <16 years)
6. 6. Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization.
7. 7. Creatinine clearance (CrCl) ≥30 milliliter/minute based on the Cockcroft-Gault formula in adult patients and Schwartz formula in pediatric participants.
8. 8. Male and/or female participants. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
9. 9. Concomitant use a of systemic corticosteroid is allowed but not required. Topical and inhaled corticosteroid agents are allowed. If a patient is taking corticosteroids at study randomization, they must be on a stable dose of corticosteroids for at least 2 weeks prior to Cycle 1 Day 1.
10. 10. Concomitant use of calcineurin inhibitor (CNI) or mammalian target of repamycin (mTOR) inhibitors (sirolimus or everolimus) is allowed but not required.
11. 11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol. A parent/guardian should provide consent for pediatric participants unable to provide consent themselves; in addition, where applicable pediatric participants should sign their own assent form.

Exclusion criteria 15

1. 1. Has acute GVHD without manifestations of cGVHD.
2. 2. Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
3. 3. History of acute or chronic pancreatitis.
4. 4. History of myositis.
5. 5. History or other evidence of severe illness, uncontrolled infection or any other conditions that would make the patient, in the opinion of the Investigator, unsuitable for the study.
6. 6. Participants with acquired immune deficiency syndrome (AIDS).
7. 7. Patients with a of history of latent or active tuberculosis (TB) before screening; signs or symptoms suggestive of active TB upon medical history and/or physical examination; recent close contact with a person with active TB; positive QuantiFeron TB test at screening.
8. 8. Hepatitis B (defined as hepatitis B virus [HBV] surface antigen positive and HBV core antibody positive, with positive HBV deoxyribonucleic acid [DNA], or HBV positive core antibody alone with positive HBV DNA. Hepatitis C (defined as positive hepatitis C [HCV] antibody with positive HCV ribonucleic acid [RNA]).
9. 9. Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of randomization, unless previously treated with curative intent and approved by Sponsor's Medical Monitor (for example, completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection).
10. 10. Female patient who is pregnant or breastfeeding.
11. 11. Previous exposure to CSF-1R–targeted therapies.
12. 12. Taking agents for treatment of cGVHD other than corticosteroids or either a CNI or mTOR inhibitor is prohibited.
13. 13. For approved or commonly used agents, other than corticosteroids, CNI and mTOR inhibitor, a washout of 2 weeks or 5 half-lives, whichever is shorter, is required at study enrollment.
14. 14. Receiving an investigational treatment within 28 days of randomization.
15. 15. Patients should not be participating in any other interventional study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. ORR in the first 6 cycles as defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGVHD

Secondary endpoints 7

1. 1. mLSS
2. 2. - ORR, - DOR, - SRR, - Organ-specific and joints and fascia response rate, - Average daily corticosteroid dose, - Discontinue corticosteroid, - Average daily CNI dose, - Discontinue CNI.
3. 3. - AEs and SAEs, - Vital signs, safety laboratory parameters, physical/neurological examination, ECG, and Karnofsky/Lansky performance scale.
4. 4. PK parameters and patient factors.
5. 5. CSF-1, IL-34 levels.
6. 6. Circulating monocyte number and phenotype.
7. 7. Baseline circulating monocyte number and phenotype.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Syndax Pharmaceuticals Inc.

Sponsor organisation

Syndax Pharmaceuticals Inc.

Address

35 Gatehouse Drive

City

Waltham

Postcode

02451-1215

Country

United States

Scientific contact point

Organisation

Syndax Pharmaceuticals Inc.

Contact name

Patrick Hardesty, PharmD, MS

Public contact point

Organisation

Syndax Pharmaceuticals Inc.

Contact name

Patrick Hardesty, PharmD, MS

Third parties 11

Locations

6 EU/EEA countries · 23 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 50 files

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

Application history

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