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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04710576




Registration number
NCT04710576
Ethics application status
Date submitted
5/01/2021
Date registered
14/01/2021
Date last updated
10/10/2024

Titles & IDs
Public title
A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD)
Scientific title
AGAVE-201, A Phase 2, Open-label, Randomized, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of Axatilimab at 3 Different Doses in Patients With Recurrent or Refractory Active Chronic Graft Versus Host Disease Who Have Received at Least 2 Lines of Systemic Therapy
Secondary ID [1] 0 0
SNDX-6352-0504
Universal Trial Number (UTN)
Trial acronym
AGAVE-201
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Graft-versus-host-disease 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Axatilimab

Experimental: Axatilimab Dose Cohort 1 - Participants will be administered axatilimab 0.3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks for up to 2 years.

Experimental: Axatilimab Dose Cohort 2 - Participants will be administered axatilimab 1 mg/kg IV every 2 weeks for up to 2 years.

Experimental: Axatilimab Dose Cohort 3 - Participants will be administered axatilimab 3 mg/kg IV every 4 weeks for up to 2 years.


Treatment: Drugs: Axatilimab
Axatilimab is a high-affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor-derived macrophages that mediate the disease processes involved in cGVHD.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) in the First 6 Cycles as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease (cGVHD)
Timepoint [1] 0 0
First 6 cycles (up to Cycle 7 Day 1; each cycle = 4 weeks)
Secondary outcome [1] 0 0
ORR on Study as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
Number of Participants With a Clinically Significant Improvement in Normalized Score on the Modified Lee Symptom Scale
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Duration of Response
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
Sustained Response Rate
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Organ-specific Response Rate
Timepoint [5] 0 0
Up to 2 years
Secondary outcome [6] 0 0
Joints and Fascia Response Rate Based on Refined NIH Response Algorithm for cGVHD
Timepoint [6] 0 0
Up to 2 years
Secondary outcome [7] 0 0
Percent Reductions in Average Daily Doses (or Equivalent) of Corticosteroid
Timepoint [7] 0 0
Up to 2 years
Secondary outcome [8] 0 0
Number of Participants Who Discontinue Corticosteroid Use
Timepoint [8] 0 0
Up to 2 years
Secondary outcome [9] 0 0
Percent Reductions in Average Daily Doses (or Equivalent) of Calcineurin Inhibitors (CNI)
Timepoint [9] 0 0
Up to 2 years
Secondary outcome [10] 0 0
Number of Participants Who Discontinue CNIs
Timepoint [10] 0 0
Up to 2 years
Secondary outcome [11] 0 0
Change From Baseline in Circulating Monocyte Number and Phenotype (CD14/16)
Timepoint [11] 0 0
Baseline, up to 2 years
Secondary outcome [12] 0 0
Number of Participants With Anti-Drug Antibody
Timepoint [12] 0 0
Up to 2 years
Secondary outcome [13] 0 0
Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of Last Measurable Concentration (AUC0-t)
Timepoint [13] 0 0
Approximately 12 months
Secondary outcome [14] 0 0
Number of Participants With Treatment-emergent Adverse Events
Timepoint [14] 0 0
Up to 2 years
Secondary outcome [15] 0 0
Change From Baseline in Bone Turnover Markers
Timepoint [15] 0 0
Baseline, up to 2 years
Secondary outcome [16] 0 0
Change From Baseline in Bone Density
Timepoint [16] 0 0
Baseline, up to 2 years
Secondary outcome [17] 0 0
Change From Baseline in Colony Stimulating Factor 1 (CSF-1) and Interleukin 34 (IL-34) Levels
Timepoint [17] 0 0
Baseline, up to 2 years

Eligibility
Key inclusion criteria
1. Participants must be 2 years of age or older, at the time of signing the informed consent.
2. Participants who are allogeneic hematopoietic stem cell transplantation (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. Participants with refractory or recurrent active cGVHD despite at least 2 lines of systemic therapy.

* Refractory disease 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.
* Participants 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. Participants 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. Karnofsky Performance Scale of =60 (if aged 16 years or older); Lansky Performance Score of =60 (if aged <16 years)
6. Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization.
7. Creatinine clearance (CrCl) =30 milliliter/minute based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants.
8. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
9. Concomitant use a of systemic corticosteroid is allowed but not required. Topical and inhaled corticosteroid agents are allowed. If a participant 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. Concomitant use of CNI or mammalian target of repamycin (mTOR) inhibitors (sirolimus or everolimus) is allowed but not required.
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.
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:

1. Has acute GVHD without manifestations of cGVHD.
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. History of acute or chronic pancreatitis.
4. History of myositis.
5. History or other evidence of severe illness, uncontrolled infection or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
6. Participants with acquired immune deficiency syndrome (AIDS).
7. 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]).
8. 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).
9. Female participant who is pregnant or breastfeeding.
10. Previous exposure to CSF1-R targeted therapies.
11. Taking agents for treatment of cGVHD other than corticosteroids or either a CNI or mTOR inhibitor is prohibited.
12. 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.
13. Receiving another investigational treatment within 28 days of randomization.
14. Participants should not be participating in any other interventional study. Pediatric participants are encouraged to also participate in the ongoing developmental studies of the Pediatric cGVHD Symptom Scale (PCSS).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2027
Actual
Sample size
Target
Accrual to date
Final
241
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Royal Children's Hospital - Parkville
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment postcode(s) [2] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
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Indiana
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United States of America
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Louisiana
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United States of America
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Maryland
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United States of America
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Massachusetts
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Michigan
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Minnesota
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Missouri
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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Wisconsin
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Belgium
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Leuven
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Belgium
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Roeselare
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Canada
State/province [29] 0 0
British Columbia
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Canada
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Ontario
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Canada
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Quebec
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France
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Auvergne-Rhône-Alpes
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France
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Grand Est
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France
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Haure-Garrone
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France
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Hauts-de-France
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France
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Nancy
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France
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Nantes
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France
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France
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Pessac
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Germany
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Thessaloniki
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Patras
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Israel
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Israel
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Ramat Gan
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Israel
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Brescia
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Monza
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Italy
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Pavia
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Italy
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Roma
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Italy
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Torino
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Korea, Republic of
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Busan
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Gliwice
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Madrid
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Majadahonda
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Spain
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Salamanca
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Spain
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Santander
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Spain
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Valencia
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Taipei
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United Kingdom
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Bristol
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Cardiff
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Glasgow
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Syndax Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 2 study to evaluate the efficacy, safety, and tolerability of axatilimab at 3 different dose levels in participants with recurrent or refractory active chronic graft versus host disease (cGVHD) who have received at least 2 prior lines of systemic therapy.
Trial website
https://clinicaltrials.gov/study/NCT04710576
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Vedran Radojcic, M.D.
Address 0 0
Syndax Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04710576