A Phase 2 Study of Intravenous AMB-05X in Tenosynovial Giant Cell Tumor Patients

Study Overview
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Brief Summary
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The purpose of this Phase 2, open-label, multiple-dose, dose-escalation study is to evaluate intravenous AMB-05X in the treatment of patients with TGCT.

Official Title
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A Phase 2, Adaptive, Open-Label, Multiple-Dose, Dose-Escalation Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Intravenous AMB-05X in Subjects With Tenosynovial Giant Cell Tumor

Conditions
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TGCT, Tenosynovial Giant Cell Tumor, Pigmented Villonodular Synovitis, PVNS - 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 Measurable disease based on RECIST v1.1 Symptomatic disease Stable prescription of analgesic regimen 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 Current or prior radiotherapy within 3 months before Baseline Current or prior active cancer within 3 years before Baseline that requires/required therapy (eg, surgery, chemotherapy, or radiation therapy) Known metastatic TGCT or malignant transformation of diffuse-type TGCT Hepatitis C virus (HCV) or hepatitis B virus (HBV) or known active or chronic infection with human immuno deficiency virus (HIV) Known active tuberculosis (TB) Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history Women who are pregnant or breastfeeding Screening Fridericia-corrected QT interval(QTcF) ≥450ms (men) or ≥470ms (women) MRI contraindications (eg, pacemaker, loose metallic implants) History of hypersensitivity to any ingredient in the study drug History of drug or alcohol abuse within 3 months before Baseline Has 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, interfere with interpretation of study results, or, in the Investigator's opinion, make the subject inappropriate for this study A person who is held in detention as the result of a judicial or official decision or who is in a subordinate relationship to the Sponsor or Investigator A subject who, in the opinion of the Investigator, should not participate in the study for any reason, including if there is a question about the subject's 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: Sequential Assignment
Interventional Model Description: A data monitoring committee will review study data on an ongoing basis and advise on the appropriate dose for each cohort.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Low-Dose AMB-05X Each subject will receive a low dose of AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period. | 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 |
| --- | --- | --- |
| Overall tumor response per RECIST | Proportion of subjects achieving 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 |
| --- | --- | --- |
| Treatment-emergent adverse events | Frequency and severity of reported treatment-emergent adverse events | Up to week 24 | 
| 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 the 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. | Week 12 | 
| EQ-5D-5L (EuroQol-5 Dimension-5 Level) Health Assessment | EQ-5D-5L (EuroQol-5 Dimension-5 Level) 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, TGCT, PVNS