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

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

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

Study Overview

• Status: Terminated
• Conditions: Tenosynovial Giant Cell Tumor; Pigmented Villonodular Synovitis; TGCT; PVNS - Pigmented Villonodular Synovitis
• 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 Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary
    • 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

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 TGCT
3. Measurable disease based on RECIST v1.1
4. Symptomatic disease
5. Stable prescription of analgesic regimen
6. Agrees to follow contraception guidelines
7. Adequate hematologic, hepatic, and renal function, at Screening
8. 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. Current or prior radiotherapy within 3 months before Baseline
3. Current or prior active cancer within 3 years before Baseline that requires/required therapy (eg, surgery, chemotherapy, or radiation therapy)
4. Known metastatic TGCT or malignant transformation of diffuse-type TGCT
5. Hepatitis C virus (HCV) or hepatitis B virus (HBV) or known active or chronic infection with human immuno deficiency virus (HIV)
6. Known active tuberculosis (TB)
7. Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history
8. Women who are pregnant or breastfeeding
9. Screening Fridericia-corrected QT interval(QTcF) ≥450ms (men) or ≥470ms (women)
10. MRI contraindications (eg, pacemaker, loose metallic implants)
11. History of hypersensitivity to any ingredient in the study drug
12. History of drug or alcohol abuse within 3 months before Baseline
13. 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
14. 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
15. 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

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: Cohort A; 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; 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
Treatment-emergent Adverse Events (TEAEs)	The frequency and severity of reported TEAEs in Subjects with Tenosynovial Giant Cell Tumor (TGCT) receiving Intravenous AMB 05X.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Tumor Response (Objective Response) Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1	Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; Per RECIST v1.0 for target lesions and assessed by MRI: A Complete Response (CR) is defined as disappearance of all tumors. A Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target tumors from the baseline sum of diameters.	12 weeks
Overall Response Based on Tumor Volume Score (TVS)	Tumor Volume Score (TVS) calculates tumor volume as a percentage of the estimated volume of the maximally distended synovial cavity or tendon sheath and provides a score in 10% increments. A score of 0 indicates no evidence of tumor; a score of 10 indicates a tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath. Complete response (CR): lesion is completely gone; Partial response (PR): >/=50% decrease in TVS relative to Baseline; Progressive disease (PD): >/= 30% increase in TVS relative to the lowest score during the study; Stable disease (SD): does not meet any of the other classifications.	24 weeks or ET visit
Mean Change From Baseline Range of Motion (ROM) (Flexion, Knee) Scores	Mean Change from Baseline in Range of Motion (ROM) Scores - Flexion (knee only). ROM is assessed by qualified assessors and recorded in degrees. At Baseline, the plane of movement with the smallest (worst) relative ROM was identified; only this plane was used for evaluating change in ROM. Higher scores indicate greater range of motion.	week 12
Mean Change From Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Score	Mean change from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function score is used to assess physical function. PROMIS is a 10-question patient reported outcome instrument used to assess physical functioning based on use of the upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back) and on instrumental activities of daily living. Five questions address the degree to which the subject's health limits activities, and subjects select a response 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"). Raw scores are summarized. The score range is 10 to 50, higher scores = worse physical function	12 weeks
Serum Cmax for AMB-05X at Week 10 Post Dose	The maximum concentration of AMB-05X in subject serum is measured at week 10 postdose, using sensitive enzyme-linked immunosorbent assay analyses (ELISA).	10 weeks
Number of Subjects With Anti-Drug Antibodies to AMB-05X at Week 10	AMB-05X Anti-drug Antibodies (ADA) in subject serum will be measured from pre-dose samples.	10 weeks
Mean Change From Baseline in Worst Stiffness Numeric Rating Scale (NRS) Score	The mean changes from Baseline in the Worst Stiffness Numeric Rating Scale (NRS) score, a Patient-Reported Outcome (PRO) Measurement. The Worst Stiffness NRS is a single-item instrument designed to assess "worst" stiffness at the site of the tumor in the last 24 hours. The instrument uses an 11-point numeric rating scale that ranges from 0 ("no stiffness") to 10 ("stiffness as bad as you can imagine"). Higher scores indicate worse stiffness.	12 weeks
Brief Pain Inventory Pain Severity Domain Score	The mean changes from Baseline in Brief Pain Inventory (BPI) Pain Severity Domain. (Score of 0-10, where a negative score from baseline indicates a better BPI score, less severe pain) Brief Pain Inventory (BPI) 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. For the Pain Severity domain the subject is asked to rate their worst, least, average, and current pain intensity, and list current treatments and their perceived effectiveness on a scale from 0 to 10, where higher scores mean more severe pain. All of the 0-10 scores are averaged to obtain the total Domain (subscale) Score.	12 weeks
Mean Change From Baseline in Brief Pain Inventory Severity Interference	The mean changes from Baseline in Brief Pain Inventory (BPI) Severity Interference domain. The BPI Short Form is a patient-reported outcome instrument used to evaluate the severity of a subject's pain and the impact of this pain on the subject's daily functioning. For this domain, 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. Higher scores indicate greater levels of pain.	12 weeks
Worst Pain Numeric Rating Scale Score	Mean change from Baseline in Worst Pain Numeric Rating Scale score. The Worst Pain Numeric Rating Scale is an item in the BPI that assesses a subject's "worst" pain in the last 24 hours. The 11-point Numeric Rating Scale for this item ranges from 0 ("no pain") to 10 ("pain as bad as you can imagine"). Higher scores indicate greater level of pain.	12 weeks
EuroQol 5 Dimension 5 Level Health Assessment	Mean change from Baseline in the EuroQol 5 Dimension 5 Level (EQ-5D-5L) assessment Scale Score (5-25). This instrument is a self-report survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 5-level severity ranking that ranges from "no problems" through "extreme problems". Higher scores indicate a lower quality of life.	12 weeks
Colony-stimulating Factor 1 Levels	Serum colony-stimulating factor-1 (CSF-1) levels are measured in patient/subject serum. Samples were collected for measurement of CSF-1 at least once at specified visits.	10 weeks
Mean Change From Baseline Rnge of Motion (Flexion, Ankle) Scores	Mean Change from Baseline in Range of Motion (ROM) Scores - Flexion (Ankle only). ROM is assessed by qualified assessors and recorded in degrees. At Baseline, the plane of movement with the smallest (worst) relative ROM was to be identified; only this plane was used for evaluating change in ROM. Higher scores indicate greater range of motion.	week 12
Serum AMB-05X-Binding Anti-drug Antibody (ADA) Levels	Series analysis for anti-drug antibody detection and titer	Week 12

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): September 16, 2021
• Primary Completion (Actual): April 20, 2022
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: June 16, 2021
• First Submitted That Met QC Criteria: June 22, 2021
• First Posted (Actual): June 24, 2021

Study Record Updates

• Last Update Posted (Actual): May 24, 2024
• Last Update Submitted That Met QC Criteria: May 22, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Tenosynovial Giant Cell Tumor, TGCT, 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-051-02

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