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Completed

NCT Number: NCT03604692

A Phase 1/2 Study to Evaluate Axatilimab in Participants With Active cGVHD

This is a Phase 1/2, Open-label, Dose Escalation study to investigate axatilimab in participants with active chronic graft versus host disease (cGVHD).

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Key information

Conditions

Chronic Graft-versus-host-disease Bronchial Diseases Bronchiolitis Bronchiolitis Obliterans Bronchiolitis Obliterans Syndrome Bronchitis Graft vs Host Disease Immune System Diseases Lung Diseases Lung Diseases, Obstructive Organizing Pneumonia Respiratory Tract Diseases

Age range

6 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

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About this study

This is a dose escalation and dose expansion study in participants with active cGVHD who have received at least 2 lines of prior therapy.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Participant must be 6 years of age or older, at the time of signing the informed consent.
  • Participants who are allogeneic hematopoietic stem cell transplant (HSCT) recipients with cGVHD requiring systemic immune suppression.
  • Participants with active cGVHD who have received at least 2 lines of therapy. Participants 18 or older with active cGVHD who have erythematous rash involving >25% body surface area or a NIH mouth score of >4 must have received prior ibrutinib therapy.

a. 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 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 with a life expectancy of at least 3 months (if aged 16 years or older); Lansky Performance Score of ≥60 (if less than 16 years).
  • Adequate organ and bone marrow functions.
  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Capable of giving signed informed consent which includes compliance with the study requirements and restrictions.

Key Exclusion Criteria:

  • 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 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.
  • Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
  • Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of enrollment, unless previously treated with curative intent and must be approved by Sponsor 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 participants who are pregnant or breastfeeding.
  • Previous exposure to study intervention or known allergy/sensitivity to study intervention.
  • Taking agents other than a corticosteroid and one calcineurin inhibitor (CNI) for treatment of cGVHD (This does not include agents being prescribed expressly for the treatment of acute GVHD).
  • Receiving an investigational treatment within 28 days of study entry.

Treatment and study plan

Axatilimab

Drug

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: Niktimvo, SNDX-6352

Primary outcomes

  1. Phase 1: Number of Participants With DLTs

    Time frame: Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1)

    A DLT was defined as the occurrence of any protocol-specified event within the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from Cycle 1 Day 1 to Cycle 2 Day 1) and assessed by the Investigator as not being definitely attributable to underlying disease, disease progression, inter-current illness, concomitant medications or any other alternative cause.

  2. Phase 1: Recommended Phase 2 Dose (RP2D)

    Time frame: Day 1 through the first 28 days from the first dose of SNDX-6352 or administration of the third dose (Cycle 2 Day 1), whichever is later (from C1D1 to C2D1)

    The RP2D was determined in discussion with the Sponsor, Medical Monitor, and Dose Determination Phase Investigators and was based on observations from the Phase 1 of the study (clinical benefit in chronic graft versus host disease [cGVHD] and pharmacokinetic/pharmacodynamic effects).

  3. Phase 2: Overall Response Rate (ORR) as Assessed by the Number of Participants With Complete Response (CR) or Partial Response (PR) at Cycle 7 Day 1 (Day 168)

    Time frame: Cycle 7 Day 1 (Day 168)

    CR or PR was defined by the 2014 National Institutes of Health (NIH) Consensus Development Project on Criteria for Clinical Trials in cGVHD.CR was defined as resolution of all manifestations in each organ or site, and PR was defined as improvement in at least 1 organ or site without progression in any other organ or site. ORR was defined as the percentage of participants achieving a best overall response of CR or PR .ORR calculated as: (number of participants with best overall response as CR or PR)/total number of participants.

Secondary outcomes

  1. Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration for SNDX-6352

    Time frame: Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15

    Blood samples were collected for determination of SNDX-6352 concentration.

  2. Phase 1: Observed Maximum Plasma Concentration for SNDX-6352

    Time frame: Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15

    Blood samples were collected for determination of SNDX-6352 concentration.

  3. Phase 1: Time to Observed Maximum Plasma Concentration

    Time frame: Cycle 1: predose, at 30 min (end of infusion), and at 1 hour and 8 hours on Day 1 and Day 15

    Blood samples were collected for determination of SNDX-6352 concentration.

  4. Phase 1: Changes From Baseline in Colony-Stimulating Factor-1 (CSF-1) and Interleukin (IL-34) Serum Concentrations

    Time frame: Baseline, Cycle 1 Day 8, Day 15, predose at Cycle 2 Day 1, Cycle 4 Day 1 (28-day cycles), and end of treatment (EOT) (median duration of treatment = 7 months)

    Blood samples were collected for determination of serum concentrations.

  5. Phase 1: Percent Change From Baseline in Nonclassical Monocytes (CD14+CD16++)

    Time frame: Baseline, Day 8, Day 15, predose at Cycle 2 Day 1, Cycle 4 Day 1, and EOT (median duration of treatment = 7 months)

    Blood samples were collected for determination nonclassical monocytes levels.

  6. Phase 1: Number of Participants Positive for Anti-Drug Antibodies (ADA)

    Time frame: Predose on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Day 1 of each subsequent cycle through EOT plus 30 days after last dose (safety follow-up) (median duration of treatment = 7 months)

    Blood samples were collected for ADA assessment. A participant was considered ADA positive if at least 1 postbaseline sample was ADA positive.

  7. Phase 2: Best Overall Response (BOR), as Defined by the 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD

    Time frame: Day 1 of each 28-Day cycle up to Cycle 7 Day 1

    Physician-reported global cGVHD activity assessment and cGVHD response determination. Best overall response was calculated as percent of participants with a response of CR or PR.

  8. Phase 2: Failure Free Survival (FFS)

    Time frame: From first dose of study intervention (Day 1) up to 27 months

    FFS was defined as the time from first dose of study intervention to unequivocal progression of cGVHD or relapse of underlying malignancy or addition of another systemic immune suppressive therapy or discontinuation of study treatment due to toxicity or death for any reason. Unequivocal progression of cGVHD is defined as treatment discontinuation due to clinical progression. The duration of FFS was evaluated using organ-specific cGVHD activity assessment form and and summarized descriptively using the Kaplan-Meier method.

  9. Phase 2: Duration of Response (DOR)

    Time frame: Day 1 of each 28-Day cycle for up to 12 cycles

    DOR was defined as the time of initial response until documented progression or start of another systemic treatment as assessed by the Kaplan-Meir method.

  10. Phase 2: Sustained Response Rate (SRR)

    Time frame: Day 1 of each 28-Day cycle for up to 12 cycles

    SSR of CR or PR ≥20 weeks was defined as rate of CR or PR lasting for at least 20 weeks from the time of initial response.

  11. Phase 2: Organ-specific Response Rate Based on 2014 NIH Consensus Development Project on Criteria for Clinical Trials in cGVHD

    Time frame: Day 1 of each 28-Day cycle for up to 12 cycles

    The percentage of participants with a response (CR/PR) in the skin, eyes, mouth, esophagus, upper gastrointestinal (GI), lower GI, liver, lungs, or joints and fascia were assessed using the NIH Consensus Development Project on Clinical Trials.

  12. Phase 2: Number of Participants With a Joint and Fascia Response Based on Refined NIH Response Algorithm for cGVHD

    Time frame: Day 1 of each 28-Day cycle for up to 12 cycles

  13. Phase 2: Number of Participants With A Lee Symptom Scale Summary Score Decrease of at Least 7 Points From Baseline

    Time frame: Day 1 of each 28-Day cycle for up to 12 cycles

    The Lee cGVHD symptom questionnaire asked participants to indicate the degree of "bother" that they experienced during the past 7 days due to symptoms in 7 domains potentially affected by chronic GVHD (skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, emotional distress) using a 5-point Likert scale from 0 "not at all" to 4 "extremely." Scores were normalized (0 to 100 scale) and the number of participants with a ≥ 7-point decrease in normalized score was calculated. A decrease in score indicated improvement in symptoms.

  14. Phase 2: Number of Participants With a ≥50% Reduction in Prednisone Equivalent Dosage Lasting at Least 28 Days

    Time frame: Day 1 of each 28-Day cycle for up to 12 cycles

  15. Phase 2: Number of Participants Who Discontinued Calcineurin Inhibitor Use

    Time frame: Day 1 of each 28-Day cycle for up to 12 cycles

Sponsors and collaborators

Lead sponsor

Syndax Pharmaceuticals

Industry

Registry information

Official study title

A Phase 1/2, Open-Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamic Activity, and Efficacy of SNDX- 6352 in Subjects With Active Chronic Graft Versus Host Disease Who Have Received at Least 2 Lines of Prior Therapy

Important dates

Study start
2018
Primary completion
2022
Study completion
2024
First posted
Jul 27, 2018
Registry last updated
Sep 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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