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

Study Overview
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Brief Summary
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AMB-051-01 is a multicenter study with an adaptive design that will enroll approximately 12 subjects with TGCT of the knee for 12 weeks of multiple-dose, open-label treatment with AMB-05X.

Official Title
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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

Conditions
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Tenosynovial Giant Cell Tumor, Pigmented Villonodular Synovitis

Intervention / Treatment
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* Biological: AMB-05X


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject ≥ 18 years A confirmed diagnosis of TGCT of the knee joint Measurable disease based on RECIST v1.1 Stable prescription of analgesic regimen Negative urine drug screen (UDS) at Screening and Baseline Women of childbearing potential must have a negative pregnancy test Agrees to follow contraception guidelines Adequate hematologic, hepatic, and renal function, at Screening Willing and able to complete self-assessment instruments throughout the study Exclusion Criteria: Prior investigational drug use within 4 weeks or 5 half-lives of Baseline Previous use of therapeutics targeting CSF1 or CSF1R or oral tyrosine kinase inhibitors History of extensive knee surgery Active cancer (either currently or within 1 year before Baseline) that requires therapy (e.g., surgery, chemotherapy, or radiation therapy) Metastatic TGCT Hepatitis C virus (HCV) or hepatitis B virus (HBV) or human immunodeficiency virus (HIV) Known active tuberculosis Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history Women who are breastfeeding A screening Fridericia-corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms (women) MRI contraindications (e.g., pacemaker, loose metallic implants) History of hypersensitivity to any ingredient of the study drug History of drug or alcohol abuse within 3 months before the first dose of study drug 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMB-05X<br>Subjects will receive an injection of AMB-05X once every 2 weeks for 12 weeks (for 6 treatments total). Based on ongoing review of the available safety, PK, PD, and efficacy data, the Sponsor may either increase or decrease the dose. | Biological: AMB-05X<br>* A fully human monoclonal immunoglobulin (IgG2) directed against c-fms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent adverse events | Frequency and severity of reported treatment-emergent adverse events | Week 12 | 
| Tumor response based on RECIST | Proportion of subjects who achieve an overall tumor response per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response based on tumor volume | Proportion of subjects with overall response based on tumor volume score | Week 12 | 
| Mean change from Baseline in range of motion (ROM) | 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 ranges from 1 ('unable to do' or 'cannot do') to 5 ('without any difficulty' or 'not at all'), where higher scores represent better outcomes. | 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 Worst Pain NRS score | The Worst Pain NRS is a component of the Brief Pain Inventory assessing the worst pain in the last 24 hours. The NRS for this item ranges from 0 (no pain) to 10 (pain as bad as you can imagine). | Week 12 | 
| Mean change from Baseline in the Brief Pain Inventory (BPI) 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. | Weeks 12 | 
| EQ-5D-5L Health Assessment | 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. The choices include 5 levels of severity for each domain followed by a general health visual analogue scale (VAS). | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tenosynovial Giant Cell Tumor, Pigmented villonodular synovitis, TGCT, PVNS