The objectives of this study are to evaluate the safety, efficacy, and pharmacokinetics (PK) of AMB-05X in the treatment of tenosynovial giant cell tumor (TGCT)
ID
Source
Brief title
Condition
- Synovial and bursal disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Frequency and severity of reported treatment-emergent adverse events (TEAEs)
Secondary outcome
Efficacy:
The following efficacy endpoints will be assessed at Week 12:
• The proportion of subjects who achieve an overall tumor response (objective
response [OR], which includes both complete response [CR] and partial
response [PR]) per the Response Evaluation Criteria in Solid Tumors Version 1.1
(RECIST v1.1) at Week 12.
• Proportion of subjects with overall response based on tumor volume score
(TVS), a TGCT-specific method that calculates tumor volume as a
percentage of the estimated maximally distended synovial cavity
• Mean change from Baseline in range of motion (ROM) score
• Mean change from Baseline in the Patient-Reported Outcomes Measurement
Information System (PROMIS) Physical Function score
• Mean change from Baseline in Worst Stiffness Numeric Rating Scale (NRS) score
• Percentage of subjects who respond with a decrease of at least 30% in mean
Brief Pain Inventory (BPI) score from Baseline
• Mean change from Baseline in BPI score
• Mean change from Baseline in Worst Pain NRS score
• Mean change from Baseline in EQ-5D-5L health assessment
Pharmacokinetics and Pharmacodynamics:
• Serum (and optional synovial) AMB-05X levels
• Serum (and optional synovial) AMB-05X-binding anti-drug antibody (ADA) levels
• Serum (and optional synovial) colony-stimulating factor 1 (CSF1) levels
Background summary
AMB-05X drug substance is a human monoclonal antibody against the
colony-stimulating factor 1 receptor (CSF1R). This drugcandidate is thought to
block the growth-promoting activity in TGCT. Given the limitations of current
treatment options, thelocalized nature of the disease and prior clinical
validation of CSF1R as an effective treatment target, AMB-05X is being
developedby the sponsor.
Study objective
The objectives of this study are to evaluate the safety, efficacy, and
pharmacokinetics (PK) of AMB-05X in the treatment of tenosynovial giant cell
tumor (TGCT)
Study design
This is a Phase 2, open-label, multiple-dose, dose-escalation study with an
adaptive design that will enroll up to approximately 36 subjects with TGCTfor
12 weeks of open-label treatment with intravenous (IV) AMB-05X. Each subject
will receive a dose of AMB-05X every 2 weeks, for a total of 6 doses over the
12-week treatment period.
The study will enroll up to 3 dose cohorts each composed of 3 to 12 subjects.
The following dose cohorts are planned:
-Cohort A: Initial dose of 4 mg/kg, followed by 5 doses of 2 mg/kg
-Cohort B: Initial dose of 8 mg/kg, followed by 5 doses of 4 mg/kg
-Cohort C: Initial dose of 12 mg/kg, followed by 5 doses of 8 mg/kg
Based on its ongoing data review, the Sponsor may elect to enroll cohorts in a
staggered and/or overlapping manner (initiating enrollment in the next cohort
while the previous cohort is still completing or still enrolling) or
sequentially (waiting until more complete data are available from the current
cohort before initiating the next cohort).
A study schema is provided in Section 1.2, and the Schedule of Events is
provided in Section 1.3. There will be a screening period of up to 4 weeks, a
treatment period of 12 weeks, and a post-treatment follow-up period of 12 weeks.
A Sponsor data monitoring committee (DMC) composed of qualified
medical/clinical representatives will review the available safety, tolerability,
PK, pharmacodynamics (PD), and efficacy data on an ongoing basis and provide
recommendations regarding appropriate next steps in study conduct, including
any change in planned doses. The DMC will begin to review study data after the
first 3 subjects complete Week 6 and continue to review data throughout the
study (each time at least 3 additional subjects [from any cohort] complete Week
12). Study enrollment and conduct may continue unchanged during DMC review.
If a change in dose is made during the study, the DMC will again review the
available data once 3 subjects have completed Week 6 at the new dose and
provide further recommendations.
The Investigator may exercise his/her clinical judgment and consider a
reduction in an individual subject*s maintenance dose (from 2 mg/kg to 1 mg/kg,
4 mg/kg to 2 mg/kg, or 8 mg/kg to 4 mg/kg) for subjects who experience a Common
Terminology Criteria for Adverse Events (CTCAE) Grade 3 or higher adverse event
(AE) considered at least possibly related to study drug (see Section 7.4.3).
Before implementing a dose
reduction for a subject, the Investigator should contact the Medical Monitor to
discuss the case.
Intervention
The Schedule of Events is provided in Section 1.3 of the protocol
Study burden and risks
The patients will come to the hosptial 10 times, treatment will take place 6
times.
Risks associated with assessments done during these visits:
- Blood collection: Blood will be collected from a vein in the arm during this
study. Approximately 70 ml taken at some study visits (See section J of the ABR
form). Possible side effects or risks from blood collection include swelling of
the vein, pain, bruising, or bleeding at the site of collection,feeling faint
or dizzy.
- Optionally, approximately 2 ml of synovial fluid will be taken at 2 study
visits. Possible side effects or risks from synovial fluid collection are
bleeding, soreness or stiffness in the joint.
- ECG: Skin irritation could occur from the electrodes or gel that is used.
- Questionnaires/Tests of simple tasks: There are no physical risks associated
with these questionnaires/tests.
- confidentiallity, however all is done to comply with GDPR.
- common side effects: Fatigue (feeling tired), facial swelling, increases in
liver enzyme tests (changes in tests that measure thefunctioning of your
liver), rash, itch, decrease appetite. Because the drug AMB-05X is
investigational, there may be other risks thatare unknown.
- Sometimes, people have severe allergic reactions to drugs. A severe allergic
reaction could be life-threatening and may result indeath. Symptoms of possible
allergic reactions include rash, difficulty breathing, coughing, wheezing,
sudden drop in bloodpressure, swelling of the mouth, throat or eyes, seizures,
flushing, fainting, a fast pulse and sweating.
AMB-05X may lead to improvement of the disease, but this is not certain.
Twin Dolphin Drive 555, Suite 610
Redwood City CA94065
US
Twin Dolphin Drive 555, Suite 610
Redwood City CA94065
US
Listed location countries
Age
Inclusion criteria
1. Male or female >=18 years of age.
2. Able to communicate well with study staff, understand and comply with the
requirements of the study, and read and voluntarily sign the informed consent
form (ICF) before the conduct of any study-specific procedures. .
3. TGCT that meets both of the following criteria:
a. Diagnosis has been histologically confirmed by a pathologist. If the
diagnosis has not been previously histologically confirmed, biopsy with
histological confirmation is required before enrollment.
b. Has not been surgically resected either because surgical resection would be
associated with potentially worsening functional limitation/ severe morbidity
(locally advanced disease) or because the subject declined surgery.
4. Measurable disease as defined by RECIST v1.1 (except with a minimum size of
2 cm), assessed from MRI scans by a central radiologist.
5. Symptomatic disease defined as one or both of the following:
a. A score of at least 4 on the Worst Pain NRS at Screening.
b. A score of at least 4 on the Worst Stiffness NRS at Screening.
6. Stable prescription of analgesic regimen during the 2 weeks before Baseline.
7. Women of childbearing potential must have a negative serum pregnancy test at
Screening and a negative urine pregnancy test at Baseline.
8. Agrees to follow contraception guidelines (see Section 5.3).
9. Adequate hematologic, hepatic, and renal function at Screening, defined by:
• Absolute neutrophil count >= 1.5 × 109/L
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 1.5 ×
upper limit of normal (ULN)
• Hemoglobin > 10 g/dL
• Total bilirubin <= 1.5 × ULN
• Platelet count >= 100 × 109/L
• Serum creatinine <= 1.5 × ULN
10. Willing and able to complete the PROMIS Physical Function Scale, Worst
Stiffness NRS, BPI, and EQ-5D-5L throughout the study.
Exclusion criteria
1. Use of any investigational drug within 4 weeks or 5 half-lives (whichever is
longer) before baseline.
2. Any previous use of pexidartinib or any biologic treatment targeting CSF1 or
CSF1R. Use of an oral tyrosine kinase inhibitor other than pexidartinib (eg,
imatinib or nilotinib) within 3 months before Baseline.
3. Active cancer (either currently or within 1 year before Baseline) that
requires/required therapy (eg, surgery, chemotherapy, or radiation therapy),
with the exception of adequately treated basal or squamous cell carcinoma of
the skin, melanoma in situ, carcinoma in situ of the cervix or breast, or
prostate carcinoma not requiring treatment apart from active surveillance.
4. Known metastatic TGCT.
5. Hepatitis C virus (HCV) or hepatitis B virus (HBV) or known active or
chronic infection with human immunodeficiency 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 that, in the
Investigator's opinion, would likely interfere with the subject*s study
participation or the interpretation of the subject*s results.
8. A woman who is breastfeeding.
9. A screening Fridericia-corrected QT interval (QTcF) >=450 ms (men) or >=470 ms
(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 subject who, in the opinion of the Investigator, should not participate
in this study for any reason, including instances where the subject*s stability
or ability to comply with study requirements is in question.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-004870-22-NL |
| CCMO | NL75992.058.21 |
| Other | US IND 100835 |