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

• ClinicalTrials.gov Identifier: NCT04731675
• Recruitment Status: Active, not recruiting
• First Posted: February 1, 2021
• Last Update Posted: October 6, 2022
• Sponsor: AmMax Bio, Inc.
• Information provided by (Responsible Party): AmMax Bio, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Tenosynovial Giant Cell Tumor; Pigmented Villonodular Synovitis	Biological: AMB-05X	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 25, 2021
• Actual Primary Completion Date: May 5, 2022
• Estimated Study Completion Date: October 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: AMB-05X; 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; A fully human monoclonal immunoglobulin (IgG2) directed against c-fms

Outcome Measures

Primary Outcome Measures :

1. Treatment-emergent adverse events [ Time Frame: Week 12 ]
   Frequency and severity of reported treatment-emergent adverse events
2. Tumor response based on RECIST [ Time Frame: Week 12 ]
   Proportion of subjects who achieve an overall tumor response per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Secondary Outcome Measures :

1. Tumor response based on tumor volume [ Time Frame: Week 12 ]
   Proportion of subjects with overall response based on tumor volume score
2. Mean change from Baseline in range of motion (ROM) [ Time Frame: Week 12 ]
   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.
3. Mean change from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function score [ Time Frame: Week 12 ]
   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.
4. Mean change from Baseline in Worst Stiffness Numeric Rating Scale (NRS) score [ Time Frame: Week 12 ]
   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).
5. Mean change from Baseline in Worst Pain NRS score [ Time Frame: Week 12 ]
   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).
6. Mean change from Baseline in the Brief Pain Inventory (BPI) score [ Time Frame: Weeks 12 ]
   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.
7. EQ-5D-5L Health Assessment [ Time Frame: Week 12 ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subject ≥ 18 years
2. A confirmed diagnosis of 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

Contacts and Locations

Locations

United States, Ohio

AmMax Bio Clinical Site

Columbus, Ohio, United States, 43201

Netherlands

AmMax Bio Clinical Site

Leiden, Netherlands

Poland

AmMax Bio Clinical Site

Warsaw, Poland

Ukraine

AmMax Bio Clinical Site

Dnipro, Ukraine

AmMax Bio Clinical Site

Kharkiv, Ukraine

AmMax Bio Clinical Site

Kyiv, Ukraine

Sponsors and Collaborators

AmMax Bio, Inc.

Investigators

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

More Information

• Responsible Party: AmMax Bio, Inc.
• ClinicalTrials.gov Identifier: NCT04731675
• Other Study ID Numbers: AMB-051-01
• First Posted: February 1, 2021
• Last Update Posted: October 6, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AmMax Bio, Inc.:

Tenosynovial Giant Cell Tumor; Pigmented villonodular synovitis; TGCT; PVNS

Additional relevant MeSH terms:

Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Synovitis, Pigmented Villonodular; Synovitis; Neoplasms; Joint Diseases; Musculoskeletal Diseases; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Tendinopathy; Muscular Diseases