Obtain safety and efficacy data for the investigational drug 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
1. Frequency and severity of reported treatment-emergent adverse events (TEAEs)
Secondary outcome
1. 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
1.1) (Eisenhauer, 2009) at Week 12
2. 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 activity
3. Mean change from Baseline in range of motion (ROM)
4. Mean change from Baseline in the Patient-Reported Outcomes Measurement
Information System (PROMIS) Physical Function score
5. Mean change from Baseline in Worst Stiffness Numeric Rating Scale (NRS) score
6. Percentage of subjects who respond with a decrease of at least 30% in mean
Brief Pain Inventory (BPI) score
7. Mean change from Baseline in BPI
8. Mean change from Baseline in Worst Pain NRS score
9. EQ-5D-5L Health Assessment
10. Serum and synovial CSF1 levels
11. Serum and synovial AMB-05X levels
12. Serum and synovial anti-AMB-05X antibody levels
Background summary
AMB-05X drug substance is a human monoclonal antibody against the
colony-stimulating factor 1 receptor (CSF1R). This drug candidate is thought to
block the growth-promoting activity in TGCT. Given the limitations of current
treatment options, the localized nature of the disease and prior clinical
validation of CSF1R as an effective treatment target, AMB-05X is being
developed by the sponsor.
Study objective
Obtain safety and efficacy data for the investigational drug AMB-05X in the
treatment of tenosynovial giant cell tumor (TGCT)
Study design
This 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.
The study schema is provided in Section 1.2, and the Schedule of Events is
provided in Section 1.3 of the protocol.
The study will begin dosing AMB-05X at 150 mg administered via intra-articular
injection to the affected knee joint. Subjects will receive an injection of
AMB-05X once every 2 weeks for 12 weeks (for 6 treatments total).
Safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy assessments
will be reviewed by the Sponsor on a continuous, subject-by-subject basis to
determine whether the assigned dose is appropriate. Depending on these results,
the Sponsor may either decrease the dosage strength to 90 mg or increase the
dosage strength to 210 mg in subsequent subjects who enroll. In general,
subjects are expected to complete the study at the dose strength which they
started the study, unless they experience a clinically significant AE that
would warrant a dose reduction. As a general rule, clinically significant AEs
include, but are not limited to, any AE considered to be at least possibly
related to study drug and severe in intensity or meets the criteria for a SAE.
Subjects who are unable to tolerate a dosage strength of 90 mg will be
withdrawn from the study.
When at least 3 subjects have completed Week 6, a data monitoring committee
(DMC) will review the available safety, tolerability, PK, PD, and efficacy
data. Study enrollment and conduct may continue unchanged during DMC review.
Based on the recommendations of the DMC, the Sponsor may then implement any one
of the following adaptive changes without a protocol amendment:
* Continuation of enrollment under the existing design, without any changes to
the study.
* Continuation of enrollment with a new dose. Specifically, the DMC may
recommend a dose reduction to 90 mg or a dose increase to 210 mg in subsequent
subjects. Subjects may not exceed a dose of 210 mg or go below a dose of 90 mg.
Subjects who are unable to tolerate a dose of 90 mg will be discontinued from
the study.
* Discontinuation of further enrollment and/or suspension/termination of the
study.
Thereafter, the DMC should continue to review available data on a regular basis
throughout the study (each time 3 subjects complete study treatment) and
provide ongoing recommendations regarding appropriate next steps in study
conduct (as outlined above). If a change in dose is made during the study, the
DMC will again review the available data when 3 subjects have completed Week 6
at the new dose and provide further recommendations as outlined above.
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 65,0 ml of blood (see details in section J) and
approximately 12 ml of synovial fluid will be taken at some study visits.
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.
- 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 the functioning of your
liver), rash, itch, decrease appetite. Because the drug AMB-05X is
investigational, there may be other risks that are unknown.
- Sometimes, people have severe allergic reactions to drugs. A severe allergic
reaction could be life-threatening and may result in death. Symptoms of
possible allergic reactions include rash, difficulty breathing, coughing,
wheezing, sudden drop in blood pressure, 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. Subject * 18 years must be able to communicate well with study staff,
understand and comply with the requirements of the study, and read and
voluntarily sign the ICF prior to the conduct of any study specific procedures.
2. A diagnosis of TGCT of the knee joint, that has been histologically
confirmed either by a pathologist at the treating institution or by a central
pathologist. If not previously confirmed, biopsy with histological confirmation
is required.
3. Measurable disease of at least 1 cm based on RECIST v1.1, assessed from MRI
scans by a central radiologist. Subjects with one knee joint involvement only,
and only limited posterior extra-articular nodular TGCT lesions as assessed by
central radiologist and tumor review committee.
4. Stable prescription of analgesic regimen during the 2 weeks before Baseline
5. Negative urine drug screen (UDS) at Screening and Baseline
6. Women of childbearing potential must have a negative serum pregnancy test at
Screening and a negative urine pregnancy test at Baseline.
7. Agrees to follow contraception guidelines (see Section 5.3)
8. Adequate hematologic, hepatic, and renal function, at Screening Visit
defined by:
* Absolute neutrophil count * 1.5 × 109/L
* Aspartate aminotransferase or alanine aminotransferase (AST or 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
9. Willing and able to complete the Brief Pain Inventory (BPI), Worst Stiffness
NRS item, PROMIS Physical Function Scale, EQ-5D-5L, and other self-assessment
instruments throughout the study
Exclusion criteria
1. Prior investigational drug use within 4 weeks or 5 half-lives (whichever is
longer) before Baseline
2. Previous use of pexidartinib, any biologic treatment targeting CSF1 or
CSF1R, or oral tyrosine kinase inhibitors (e.g., imatinib or nilotinib)
3. History of extensive knee surgery except for prior diagnostic synovectomy
which is not exclusionary if at least 6 months prior to Baseline
4. Active cancer (either currently or within 1 year before Baseline) that
requires therapy (e.g., 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.
5. Known metastatic TGCT
6. Hepatitis C virus (HCV) or hepatitis B virus (HBV) or known active or
chronic infection with 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 that, in the
Investigator's opinion, would likely interfere with the subject*s study
participation or the interpretation of his or her results
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
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 | EUCTR2020-003275-17-NL |
| CCMO | NL75437.058.20 |
| Other | US IND 151382 |