An Open-Label Study of Intra-articular AMB-05X Injections in Subjects With Tenosynovial Giant Cell Tumor of the Knee

An Adaptive, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Intra-articular AMB-05X Injections in Subjects With Tenosynovial Giant Cell Tumor of the Knee

AMB-051-01 is a multicenter study with an adaptive design that will enroll subjects with Tenosynovial Giant Cell Tumor (TGCT) of the knee for 12 weeks of multiple-dose, open-label treatment with intra-articular AMB-05X.

Study Overview

• Status: Completed
• Conditions: Tenosynovial Giant Cell Tumor; Pigmented Villonodular Synovitis (PVNS)
• Intervention / Treatment: Biological: AMB-05X

Detailed Description

AMB-05X drug substance is a human monoclonal antibody against the colony-stimulating factor 1 receptor (CSF1R). Study

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • AmMax Bio Clinical Site
• Poland
  • Warsaw, Poland
    • AmMax Bio Clinical Site
• Ukraine
  • Dnipro, Ukraine
    • AmMax Bio Clinical Site
  • Kharkiv, Ukraine
    • AmMax Bio Clinical Site
  • Kyiv, Ukraine
    • AmMax Bio Clinical Site
• United States
  • Ohio
    • Columbus, Ohio, United States, 43201
      • AmMax Bio Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject ≥ 18 years
2. A confirmed diagnosis of tenosynovial giant cell tumor (TGCT) of the knee joint
3. Measurable disease based on RECIST v1.1
4. Stable prescription of analgesic regimen
5. Negative urine drug screen (UDS) at Screening and Baseline
6. Women of childbearing potential must have a negative pregnancy test
7. Agrees to follow contraception guidelines
8. Adequate hematologic, hepatic, and renal function, at Screening
9. Willing and able to complete self-assessment instruments throughout the study

Exclusion Criteria:

1. Prior investigational drug use within 4 weeks or 5 half-lives of Baseline
2. Previous use of therapeutics targeting CSF1 or CSF1R or oral tyrosine kinase inhibitors
3. History of extensive knee surgery
4. Active cancer (either currently or within 1 year before Baseline) that requires therapy (e.g., surgery, chemotherapy, or radiation therapy)
5. Metastatic TGCT
6. Hepatitis C virus (HCV) or hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
7. Known active tuberculosis
8. Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history
9. Women who are breastfeeding
10. A screening Fridericia-corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms (women)
11. MRI contraindications (e.g., pacemaker, loose metallic implants)
12. History of hypersensitivity to any ingredient of the study drug
13. History of drug or alcohol abuse within 3 months before the first dose of study drug
14. Any other severe acute or chronic medical or psychiatric condition or clinically significant laboratory abnormality that may increase the risk associated with study participation/treatment or interfere with interpretation of study results and, in the Investigator's opinion, make the subject inappropriate for this study
15. Subjects who, in the Investigator's opinion, should not participate in the study for any reason, including if there is a question about their ability to comply with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMB-05X; Subjects will receive an intra-articular injection of AMB-05X once every 2 weeks for 12 weeks (for 6 treatments total).	Biological: AMB-05X; AMB-05X is a fully human antibody antagonist (immunoglobulin G, type 2 [IgG2]) specific to the extracellular domain of human CSF1R

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events	Frequency and severity of reported treatment-emergent adverse events	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response Based on RECIST Version 1.1	Proportion of subjects who achieve an overall tumor response (Objective Response or OR) per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 at week 12, Objective Response is defined as complete response [CR] and partial response [PR]) per RECIST v1.1 (Eisenhauer 2009) at Week 12. Complete response: disappearance of all target lesions; Partial Response: >/=30% decrease in the sum of diameters of target lesions.	Week 12
Tumor Response Based on Tumor Volume (TV)	Proportion of subjects with overall response based on tumor volume: Complete response (CR): lesion is completely gone; Partial response (PR): >/=50% decrease in tumor volume relative to baseline; Progressive disease (PD): >/=30% increase in tumor volume relative to the lowest volume during the study; Stable disease (SD): does not meet any of the other classifications. Tumor response based on tumor volume score ("TVS") is defined as CR or PR.	Week 12
Mean Change From Baseline in Range of Motion (ROM): Flexion	ROM of the joint will be assessed by qualified assessors. Measurements will be recorded in degrees. At baseline, the plane of movement with the smallest (worst) relative value will be identified; only this plane will be used for evaluating change in ROM subsequently.	Week 12
Mean Change From Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Score	The PROMIS Physical Function Scale will be used to assess physical function. The scale incudes 10 questions, with scores that range from 1 to 5, where higher scores represent better outcomes. Five questions address the degree to which the subject's health limits certain physical activities, and subjects select a response to each question that ranges from 1 ("cannot do") to 5 ("not at all"). Five additional questions address the degree to which the subject is able to perform certain physical activities, and subjects select a response to each question that ranges from 1 ("cannot do") to 5 ("without any difficulty"). The score range for the PROMIS is 10 to 50, with higher scores indicated worse physical function.	Week 12
Mean Change From Baseline in Worst Stiffness Numeric Rating Scale (NRS) Score	The Worst Stiffness NRS is a 1-item, self-administered questionnaire assessing the "worst" stiffness within the last 24 hours. The NRS for this item ranges from 0 (no stiffness) to 10 (stiffness as bad as you can imagine).	Week 12
Mean Change From Baseline in the Brief Pain Inventory (BPI) Pain Interference Index Score	Brief Pain Inventory (BPI) Short Form is a self-administered questionnaire used to evaluate the severity of a subject's pain and the impact of this pain on the subject's daily functioning. The subject is asked to rate their worst, least, average, and current pain intensity, list current treatments and their perceived effectiveness, and rate the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a scale from 0 to 10, where higher scores mean more pain interference. The reported score is the mean of the seven interference items.	Week 12
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Health Assessment	EuroQol 5 Dimension 5 Level (EQ-5D-5L) is a widely used quality of life instrument that includes questions in each of 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate their health state by selecting the most appropriate statement in each of the five dimensions. Individual scores range from 1 to 5. The EQ-5D-5L scale score is the sum of the 5 individual EQ-5D-5L scores collected and ranges from 5 to 25. Lower scores represent a better quality of life.	Week 12
Percentage of Subjects Who Respond With a Decrease of at Least 30% in Mean Brief Pain Inventory (BPI) Score	The BPI Short Form is a self-administered questionnaire used to evaluate the severity of a subject's pain and the impact of this pain on the subject's daily functioning.	week 12
Serum Colony Stimulating Factor 1 (CSF1) Levels	Serum CSF1 levels will be analyzed as a biomarker.	week 10
Serum AMB-05X Levels	Serum AMB-05X concentrations will be measured at Week 0 (pre-dose and 2 hours after the first dose), Week 2 (pre-dose [trough]), and Week 10 during steady state (including pre-dose [trough] and 2 hour after the last dose).	week 10
Serum Anti-AMB-05X Antibody Levels	Anti-drug antibody (ADA) analysis will also be performed on select serum samples.	week 10
Synovial Fluid CSF1	Measurement of CSF1 in synovial fluid (pharmacodynamic marker)	Week 10
Synovial AMB-05X Levels	Synovial AMB-05X concentrations will be measured at Weeks 0, 2, 4, 6, 8, and 10 (all at pre-dose [trough]).	Week 10
Synovial Anti-AMB-05X Antibody (ADA) Levels	Anti-drug antibody (ADA) analysis will also be performed on select synovial samples.	Week 10
Proportions of Subjects Who Achieved Objective Response as Their Best Overall Tumor Response, Per Modified Response Evaluation Criteria in Solid Tumors (RECIST).	Objective response was measured using the modified Response Evaluation Criteria in Solid Tumors (RECIST), which requires >/=30% reduction in the sum of short-axis diameters of 2 target lesions.	12 Weeks

Collaborators and Investigators

• Sponsor: AmMax Bio, Inc.
• Investigators: Study Chair: Dorothy Nguyen, MD, AmMax Bio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2021
• Primary Completion (Actual): May 5, 2022
• Study Completion (Actual): May 5, 2022

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Actual): June 27, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: TGCT; PVNS; Tenosynovial Giant Cell Tumor (TGCT); Pigmented villonodular synovitis (PVNS)
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Neoplasms, Connective Tissue; Tendinopathy; Synovitis; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Synovitis, Pigmented Villonodular
• Other Study ID Numbers: AMB-051-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No