Back to resultsA Study to Evaluate Safety and Efficacy of AMB-05X Injections in Subjects With TGCT
Primary Purpose
Pigmented Villonodular Synovitis, TGCT, Tenosynovial Giant Cell Tumor
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AMB-05X
Sponsored by
About this trial
This is an interventional treatment trial for Pigmented Villonodular Synovitis focused on measuring Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor, TGCT, PVNS
Eligibility Criteria
Inclusion Criteria:
- Subject ≥ 18 years
- TGCT with only 1 joint involvement
- Measurable disease of at least 1 cm based on RECIST v1.1
- Stable prescription of analgesic regimen
- Agrees to follow contraception guidelines
- Women of childbearing potential must have a negative pregnancy test
- Adequate hematologic, hepatic, and renal function
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 within 3 months prior to Baseline
- History of extensive or reconstructive surgery on the affected joint
- Active cancer (either currently or within 3 mo before Baseline) that requires/required therapy (e.g., surgery, chemotherapy, or radiation therapy)
- Metastatic or malignant transformation of 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 baseline
- 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
Sites / Locations
- AmMax Bio, Clinical SiteRecruiting
- AmMax Bio, Clinical SiteRecruiting
- AmMax Bio, Clinical SiteRecruiting
- AmMax Bio, Clinical SiteRecruiting
- AmMax Bio, Clinical SiteRecruiting
- AmMax Bio, Clinical SiteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AMB-05X
Arm Description
Subjects will receive an injection of AMB-05X once every 4 weeks for 24 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.
Outcomes
Primary Outcome Measures
Objective Response Rate for Part 1
Proportion of subjects who achieve an OR (objective response rate [ORR]) by central radiology review per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Treatment-emergent adverse events
Frequency and severity of reported treatment-emergent adverse events
Secondary Outcome Measures
Objective Response Rate
Proportion of subjects who achieve an OR (objective response rate [ORR]) by central radiology review per modified Response Evaluation Criteria in Solid Tumors
Objective Response Rate (AMB-051-01 subjects)
Proportion of re-treated subjects who achieve an OR (objective response rate [ORR]) by central radiology review per modified Response Evaluation Criteria in Solid Tumors
Objective Response Rate per modified RECIST
Proportion of subjects who achieve an overall response (OR) per modified RECIST
Tumor response based on tumor volume score (TVS)
Proportion of subjects who achieve an overall tumor response (OR) per the tumor volume score
Duration of Response
Median duration of response per RECIST v1.1, modified RECIST, and TVS
Time to Response
Time to response (TTR) per RECIST v1.1, modified RECIST, and TVS
Mean change from Baseline in joint 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.
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.
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).
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.
Decrease of at least 30% in mean Brief Pain Inventory from Baseline
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.
Mean change from Baseline in PROMIS Pain Interference score
The PROMIS Item Bank v1.1 Pain Interference Short Form 8a, provided in Appendix 4, is an 8 question PRO instrument used to evaluate how much a subject's pain interferes with daily functioning (Health Measures, 2022). Subjects rate the degree to which pain interfered with their daily activity over the past 7 days on a scale of 1 to 5 (ranging from 1, "Not at all," to 5, "Very much").
Mean change from Baseline in Patient Global Impression of Change (PGIC) in Physical Functioning for capacity to perform everyday tasks
The Patient Global Impression of Change (PGIC), also known as Subject Global Impression. For this study, subjects will rate how much their TGCT has restricted their ability to perform everyday tasks, using the following scales that are based on the PGIC: PGIC Physical Functioning scale (ranging from 1, "Not at all," to 5, "Extremely".
Mean change from Baseline in PGIC in TGCT-related stiffness score
The Patient Global Impression of Change (PGIC), also known as Subject Global Impression. For this study, subjects will rate how much their TGCT has restricted their ability to perform everyday tasks, using the PGIC to rate their change in stiffness using the PGIC Stiffness scale (ranging from 1, "Very much improved" to 7, "Very much worse".
Mean change from Baseline in Worst Pain NRS score
The Worst Pain NRS is an item in the BPI that assesses a subject's "worst" pain in the last 24 hours. The 11-point NRS for this item ranges from 0 ("no pain") to 10 ("pain as bad as you can imagine").
EuroQol 5 Dimension 5 Level (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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05349643
Brief Title
A Study to Evaluate Safety and Efficacy of AMB-05X Injections in Subjects With TGCT
Official Title
A Phase 2, Open-Label, Adaptive, Dose-Ranging Study With Long-Term Extension to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Intra Articular AMB-05X Injections in Subjects With Tenosynovial Giant Cell Tumor
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 26, 2023 (Actual)
Primary Completion Date
November 2025 (Anticipated)
Study Completion Date
January 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AmMax Bio, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
AMB-051-07 is an Open-Label, Adaptive, Dose-Ranging Study with Long-Term Extension which will enroll approximately 48 adult subjects with TGCT for IA doses over a 24-week dosing period (Part 1) with a Part 2 OLE of 6 treatment and/or observational cycles of 12 weeks each followed by 12 weeks of follow-up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pigmented Villonodular Synovitis, TGCT, Tenosynovial Giant Cell Tumor
Keywords
Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor, TGCT, PVNS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
None (Open Label)
Allocation
N/A
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AMB-05X
Arm Type
Experimental
Arm Description
Subjects will receive an injection of AMB-05X once every 4 weeks for 24 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.
Intervention Type
Biological
Intervention Name(s)
AMB-05X
Intervention Description
A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
Primary Outcome Measure Information:
Title
Objective Response Rate for Part 1
Description
Proportion of subjects who achieve an OR (objective response rate [ORR]) by central radiology review per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time Frame
Part 1 Week 24
Title
Treatment-emergent adverse events
Description
Frequency and severity of reported treatment-emergent adverse events
Time Frame
Part 1 Week 24 and Part 2 Week 72
Secondary Outcome Measure Information:
Title
Objective Response Rate
Description
Proportion of subjects who achieve an OR (objective response rate [ORR]) by central radiology review per modified Response Evaluation Criteria in Solid Tumors
Time Frame
Part 2 Week 72
Title
Objective Response Rate (AMB-051-01 subjects)
Description
Proportion of re-treated subjects who achieve an OR (objective response rate [ORR]) by central radiology review per modified Response Evaluation Criteria in Solid Tumors
Time Frame
Part 2 Week 72
Title
Objective Response Rate per modified RECIST
Description
Proportion of subjects who achieve an overall response (OR) per modified RECIST
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Tumor response based on tumor volume score (TVS)
Description
Proportion of subjects who achieve an overall tumor response (OR) per the tumor volume score
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Duration of Response
Description
Median duration of response per RECIST v1.1, modified RECIST, and TVS
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Time to Response
Description
Time to response (TTR) per RECIST v1.1, modified RECIST, and TVS
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Mean change from Baseline in joint range of motion (ROM)
Description
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.
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Mean change from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function score
Description
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.
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Mean change from Baseline in Worst Stiffness Numeric Rating Scale (NRS) score
Description
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).
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Mean change from Baseline in the Brief Pain Inventory (BPI) score
Description
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.
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Decrease of at least 30% in mean Brief Pain Inventory from Baseline
Description
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.
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Mean change from Baseline in PROMIS Pain Interference score
Description
The PROMIS Item Bank v1.1 Pain Interference Short Form 8a, provided in Appendix 4, is an 8 question PRO instrument used to evaluate how much a subject's pain interferes with daily functioning (Health Measures, 2022). Subjects rate the degree to which pain interfered with their daily activity over the past 7 days on a scale of 1 to 5 (ranging from 1, "Not at all," to 5, "Very much").
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Mean change from Baseline in Patient Global Impression of Change (PGIC) in Physical Functioning for capacity to perform everyday tasks
Description
The Patient Global Impression of Change (PGIC), also known as Subject Global Impression. For this study, subjects will rate how much their TGCT has restricted their ability to perform everyday tasks, using the following scales that are based on the PGIC: PGIC Physical Functioning scale (ranging from 1, "Not at all," to 5, "Extremely".
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Mean change from Baseline in PGIC in TGCT-related stiffness score
Description
The Patient Global Impression of Change (PGIC), also known as Subject Global Impression. For this study, subjects will rate how much their TGCT has restricted their ability to perform everyday tasks, using the PGIC to rate their change in stiffness using the PGIC Stiffness scale (ranging from 1, "Very much improved" to 7, "Very much worse".
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
Mean change from Baseline in Worst Pain NRS score
Description
The Worst Pain NRS is an item in the BPI that assesses a subject's "worst" pain in the last 24 hours. The 11-point NRS for this item ranges from 0 ("no pain") to 10 ("pain as bad as you can imagine").
Time Frame
Part 1 Week 24 and Part 2 Week 72
Title
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Health Assessment
Description
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).
Time Frame
Part 1 Week 24 and Part 2 Week 72
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject ≥ 18 years
TGCT with only 1 joint involvement
Symptomatic Measurable disease of at least 1 cm based on RECIST v1.1
Stable prescription of analgesic regimen
Agrees to follow contraception guidelines
Women of childbearing potential must have a negative pregnancy test
Adequate hematologic, hepatic, and renal function
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 within 3 months prior to Baseline
History of extensive or reconstructive surgery on the affected joint
Active cancer (either currently or within 3 mo before Baseline) that requires/required therapy (e.g., surgery, chemotherapy, or radiation therapy)
Metastatic or malignant transformation of 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 baseline
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tiffany Nguyen
Phone
6502856560
Email
clinical@ammaxbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dorothy Nguyen, MD
Organizational Affiliation
AmMax Bio
Official's Role
Study Chair
Facility Information:
Facility Name
AmMax Bio, Clinical Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Recruiting
Facility Name
AmMax Bio, Clinical Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Name
AmMax Bio, Clinical Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
AmMax Bio, Clinical Site
City
Camperdown
Country
Australia
Individual Site Status
Recruiting
Facility Name
AmMax Bio, Clinical Site
City
Woolloongabba
Country
Australia
Individual Site Status
Recruiting
Facility Name
AmMax Bio, Clinical Site
City
Leiden
Country
Netherlands
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Evaluate Safety and Efficacy of AMB-05X Injections in Subjects With TGCT
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