AGAVE-201: A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD)

Sponsor

Syndax Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04710576

Collaborator

(none)

210

Enrollment

119

Locations

Arms

27.9

Anticipated Duration (Months)

1.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Graft-versus-host-disease	Drug: Axatilimab	Phase 2

Detailed Description

AGAVE-201 is a Phase 2, open-label, randomized, multicenter study to evaluate the efficacy, safety, and tolerability of axatilimab in participants with recurrent or refractory active cGVHD after failure of at least 2 prior lines of systemic therapy due to progression of disease, or intolerability, or toxicity. Active disease is defined 1) by the National Institutes of Health (NIH) 2014 consensus criteria, either in terms of organ-specific algorithm or global assessment or 2) as active, symptomatic cGVHD for whom the physician believes that a new line of systemic therapy is required.

Participants will be randomized to receive 1 of 3 different axatilimab treatment regimens in 28-day treatment cycles for up to 2 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

210 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official 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

Actual Study Start Date :

Mar 4, 2021

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: 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. Other Names: SNDX-6352
Experimental: Axatilimab Dose Cohort 2 Participants will be administered axatilimab 1 mg/kg IV every 2 weeks for up to 2 years.	Drug: 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. Other Names: SNDX-6352
Experimental: Axatilimab Dose Cohort 3 Participants will be administered axatilimab 3 mg/kg IV every 4 weeks for up to 2 years.	Drug: 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. Other Names: SNDX-6352

Arm

Intervention/Treatment

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.

Drug: 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.

Other Names:

SNDX-6352

Experimental: Axatilimab Dose Cohort 2

Participants will be administered axatilimab 1 mg/kg IV every 2 weeks for up to 2 years.

Drug: Axatilimab

Other Names:

SNDX-6352

Experimental: Axatilimab Dose Cohort 3

Participants will be administered axatilimab 3 mg/kg IV every 4 weeks for up to 2 years.

Drug: Axatilimab

Other Names:

SNDX-6352

Outcome Measures

Primary Outcome Measures

Overall Response Rate [Up to Day 169]
The overall response rate will be assessed by the number of participants with objective response by Cycle 7 (28-day cycles), Day 1, with responses defined by the 2014 NIH consensus criteria.

Secondary Outcome Measures

Duration of Response [Up to Day 169]
Duration of response is defined as the time from initial partial response or complete response until documented progression of cGVHD, start of new therapy, or death for any reason.
Number of Participants with a >5-Point Improvement in Normalized Score on the Modified Lee Symptom Scale [Up to Day 169]
Number of Participants with Treatment-emergent Adverse Events [Approximately 30 months]
Sustained Response Rate [Up to Day 169]
Sustained response rate is defined as the number of participants with objective response lasting for at least 20 weeks (140 days) from the time of initial response. Responses by organ system will be assessed based on the 2014 NIH Consensus Development Project on Clinical Trials in cGVHD.
Organ-specific Response Rate [Approximately 30 months]
Organ-specific response is defined as the number of participants with objective response for the nine individual organs based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD (skin, eyes, mouth, esophagus, upper gastrointestinal [GI], lower GI, liver, lungs and joints and fascia).
Percent Reductions in Average Daily Doses (or Equivalent) of Corticosteroid [Approximately 30 months]
Number of Participants who Discontinue Corticosteroid Use [Approximately 30 months]
Percent Reductions in Average Daily Doses (or Equivalent) of Calcineurin Inhibitors (CNI) [Approximately 30 months]
Number of Participants who Discontinue CNIs [Approximately 30 months]
Change from Baseline in Circulating Monocyte Levels [Baseline, approximately 12 months]
Number of Participants with Anti-Drug Antibody [Approximately 12 months]
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of Last Measurable Concentration (AUC0-t) [Approximately 12 months]
AUC from Time 0 to Infinity (AUC0-inf) [Approximately 12 months]
Observed Maximum Plasma Concentration (Cmax) [Approximately 12 months]
Time to Observed Maximum Plasma Concentration (Tmax) [Approximately 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants must be 2 years of age or older, at the time of signing the informed consent.
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.
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.

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.
Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance Score of ≥60 (if aged <16 years)
Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization.
Creatinine clearance (CrCl) ≥30 milliliter/minute/1.73 square meter based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants.
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
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.
Concomitant use of CNI or sirolimus is allowed but not required.
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:

Participants are excluded from the study if any of the following criteria apply:

Has acute GVHD without manifestations of cGVHD.
Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
History of acute or chronic pancreatitis.
History of myositis.
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.
Participants with acquired immune deficiency syndrome (AIDS).
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]).
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).
Female participant who is pregnant or breastfeeding.
Previous exposure to CSF1-R targeted therapies.
Taking agents for treatment of cGVHD other than corticosteroids and either a CNI or sirolimus is prohibited.
For approved or commonly used agents, other than corticosteroids, CNI and sirolimus, a washout of 2 weeks or 5 half-lives, whichever is shorter, is required at study enrollment.
Receiving another investigational treatment within 28 days of randomization.
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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham - Children's of Alabama	Birmingham	Alabama	United States	35233
2	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
3	City of Hope	Duarte	California	United States	91010
4	University of Southern California Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
5	University of California, Los Angeles (UCLA) - Medical Center	Los Angeles	California	United States	90059
6	Stanford Cancer Center	Stanford	California	United States	94305
7	Children's National Medical Center	Washington	District of Columbia	United States	20010
8	University of Florida (UF)	Gainesville	Florida	United States	32610
9	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
10	University of Miami	Miami	Florida	United States	33136
11	AdventHealth Orlando	Orlando	Florida	United States	32806
12	Moffitt	Tampa	Florida	United States	33612
13	Emory University	Atlanta	Georgia	United States	30322
14	Northside Hospital	Atlanta	Georgia	United States	30342
15	The University of Chicago Medical Center (UCMC)	Chicago	Illinois	United States	60637
16	Indiana University Health Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
17	Franciscan Health Indianapolis	Indianapolis	Indiana	United States	46237
18	Tulane University Medical Center	New Orleans	Louisiana	United States	70112
19	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
20	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
21	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
22	University of Michigan	Ann Arbor	Michigan	United States	48084
23	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
24	Henry Ford Hospital	Detroit	Michigan	United States	48202
25	University of Minnesota	Minneapolis	Minnesota	United States	55455
26	Mayo Clinic - Rochester	Rochester	Minnesota	United States	55905
27	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
28	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
29	Weill Medical College of Cornell University	New York	New York	United States	10022
30	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
31	Wake Forest	Winston-Salem	North Carolina	United States	27157
32	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
33	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
34	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
35	The Cleveland Clinic Foundation	Lyndhurst	Ohio	United States	44195
36	University of Oklahoma - Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
37	Oregon Health & Science University	Portland	Oregon	United States	97239
38	University of Pittsburgh Medical Center - Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
39	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
40	MD Anderson Cancer Center	Houston	Texas	United States	77030
41	Intermountain Healthcare	Salt Lake City	Utah	United States	84111
42	University of Utah	Salt Lake City	Utah	United States	84112
43	University of Virginia Medical Center	Charlottesville	Virginia	United States	22908
44	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
45	University of Wisconsin - Carbone Cancer Center	Madison	Wisconsin	United States	53792
46	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
47	The Royal Children's Hospital	Parkville	Victoria	Australia	3052
48	Westmead Hospital	Westmead		Australia
49	Universitaire Ziekenhuizen Leuven	Leuven		Belgium
50	AZ Delta	Roeselare		Belgium
51	Vancouver Coastal Health Authority	Vancouver	British Columbia	Canada	V5Z 1M9
52	Princess Margaret Hospital	Toronto	Ontario	Canada
53	CHU Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
54	McGill University Health Center - Research Institute	Montréal	Quebec	Canada	H3G 1A4
55	CHU de Grenoble	La Tronche	Auvergne-Rhône-Alpes	France	38700
56	Institut de cancérologie Strasbourg Europe (ICANS)	Strasbourg	Grand Est	France	67200
57	IUCT-Oncopole	Toulouse	Haure-Garrone	France	31100
58	CHU Amiens Picardie - Hopital Sud	Amiens	Hauts-de-France	France	80054
59	CHRU de Lille - Hopital Claude Huriez	Lille	Hauts-de-France	France	59037
60	CHRU de Nancy - Hôpitaux de Brabois	Nancy		France
61	CHU de Nantes - Hôtel-Dieu	Nantes		France
62	Hopital Saint Louis	Paris		France	75010
63	Hopital Pitie Salpetriere	Paris		France	75013
64	CHU Bordeaux - Hopital Haut-Leveque - Centre François Magendie	Pessac		France
65	HCL Centre Hospitalier Lyon Sud	Pierre-Bénite		France
66	Universitaetsklinikum Carl Gustav Carus Dresden	Dresden		Germany	01307
67	Universitaetsklinikum Jena	Jena		Germany	07740
68	Universitaetsklinikum Leipzig	Leipzig		Germany	04103
69	Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz	Mainz		Germany	55131
70	Universitaetsklinikum Muenster	Münster		Germany	48149
71	Universitatsklinikum Regensburg	Regensburg		Germany	93053
72	General Hospital of Thessaloniki G. Papanikolaou - Hematology Department, BMT Unit	Exochí	Thessaloniki	Greece	57010
73	University General Hospital of Patras	Patras		Greece	26500
74	Rambam Health Care Campus	Haifa		Israel	3109601
75	Hadassah Medical Center Ein Karem	Jerusalem		Israel	9112001
76	Chaim Sheba Medical Center	Ramat Gan		Israel	5262160
77	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	6423906
78	ASST degli Spedali Civili di Brescia	Brescia		Italy
79	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano	Milano		Italy	20122
80	IRCCS Ospedale San Raffaele	Milano		Italy	20132
81	ASST di Monza-Ospedale San Gerardo	Monza		Italy
82	Fondazione Monza e Brianza per il Bambino e la sua Mamma	Monza		Italy
83	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
84	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy
85	Fondazione Policlinica Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore	Roma		Italy	168
86	Pusan National University Hospital	Busan		Korea, Republic of
87	Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
88	Korea University Anam Hospital	Seoul		Korea, Republic of
89	Seoul National University Hospital	Seoul		Korea, Republic of
90	Severance Hospital	Seoul		Korea, Republic of
91	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii	Gliwice		Poland	44-102
92	Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPO-Lisboa)	Lisboa		Portugal	1099-023
93	Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE	Porto		Portugal
94	National University Hospital	Singapore		Singapore	119074
95	KK Women's and Children hospital	Singapore		Singapore	229899
96	Singapore General Hospital	Singapore		Singapore
97	Hospital Universitario Virgen del Rocio	Sevilla	Seville	Spain	41013
98	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
99	Hospital Clinic Barcelona	Barcelona		Spain	8032
100	Hospital Universitario Donostia	Donostia		Spain
101	Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves	Granada		Spain	18014
102	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
103	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
104	Hospital Universitario La Paz	Madrid		Spain	28046
105	Hospital Universitario Puerta de Hierro	Majadahonda		Spain
106	Hospital Clinico Universitario de Salamanca	Salamanca		Spain	37007
107	Hospital Universitario Marquis de Valdecilla	Santander		Spain
108	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
109	Hospital Universitari i Politecnic La Fe	Valencia		Spain	46026
110	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	80756
111	China Medical University Hospital	Taichung		Taiwan	40447
112	National Taiwan University Hospital	Taipei		Taiwan	100
113	Bristol Royal Hospital for Children	Bristol		United Kingdom	BS2 8BJ
114	University Hospital of Wales	Cardiff		United Kingdom
115	Beatson, West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
116	Queen Elizabeth University Hospital - Glasgow	Glasgow		United Kingdom
117	Hammersmith Hospital	London		United Kingdom
118	King's College Hospital NHS Foundation Trust	London		United Kingdom
119	Royal Marsden Foundation Trust	London		United Kingdom