Trial Outcomes & Findings for A Phase 2 Study of Intravenous AMB-05X in Tenosynovial Giant Cell Tumor Patients (NCT NCT04938180)
NCT ID: NCT04938180
Last Updated: 2024-05-24
Results Overview
The frequency and severity of reported TEAEs in Subjects with Tenosynovial Giant Cell Tumor (TGCT) receiving Intravenous AMB 05X.
TERMINATED
PHASE2
4 participants
6 months
2024-05-24
Participant Flow
The original study design included multiple cohorts with an adaptive, dose escalation design. However, due to the early conclusion of the study, subjects were enrolled only in Cohort A, thus no additional dose cohorts were recruited.
Participant milestones
| Measure |
Subjects With Tenosynovial Giant Cell Tumor
Cohort A: Received initial priming dose on Day 1 followed by 5 maintenance doses administered every 2 weeks (at Weeks 2, 4, 6, 8, and 10), for a total of 6 doses over the 12-week treatment period.
|
|---|---|
|
Overall Study
STARTED
|
4
|
|
Overall Study
COMPLETED
|
3
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Subjects With Tenosynovial Giant Cell Tumor
Cohort A: Received initial priming dose on Day 1 followed by 5 maintenance doses administered every 2 weeks (at Weeks 2, 4, 6, 8, and 10), for a total of 6 doses over the 12-week treatment period.
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|---|---|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
A Phase 2 Study of Intravenous AMB-05X in Tenosynovial Giant Cell Tumor Patients
Baseline characteristics by cohort
| Measure |
Cohort A: Subjects With TGCT
n=4 Participants
Low-Dose AMB-05X 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.
AMB-05X is a fully human antibody antagonist (immunoglobulin G, type 2 \[IgG2\]) specific to the extracellular domain of human CSF1R
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: All enrolled patients
The frequency and severity of reported TEAEs in Subjects with Tenosynovial Giant Cell Tumor (TGCT) receiving Intravenous AMB 05X.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=4 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Treatment-emergent Adverse Events (TEAEs)
Number of subjects with treatment-emergent adverse events
|
4 Participants
|
|
Treatment-emergent Adverse Events (TEAEs)
Number of subjects without treatment-emergent adverse events
|
0 Participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: TGCT - Modified Intent-to-treat (ITT)- All TGCT subjects who received at least 1 dose of study drug and had both baseline and post-baseline data for at least 1 efficacy endpoint.
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.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=3 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Overall Tumor Response (Objective Response) Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1
Subjects with CR
|
0 Participants
|
|
Overall Tumor Response (Objective Response) Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1
Subjects with PR
|
1 Participants
|
|
Overall Tumor Response (Objective Response) Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1
Subjects with stable disease
|
2 Participants
|
SECONDARY outcome
Timeframe: 24 weeks or ET visitPopulation: TGCT - Modified Intent-to-treat (ITT) - All TGCT subjects who received at least 1 dose of study drug and had both baseline and post-baseline data for at least 1 efficacy endpoint.
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.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=3 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Overall Response Based on Tumor Volume Score (TVS)
Subjects with CR
|
0 Participants
|
|
Overall Response Based on Tumor Volume Score (TVS)
Subjects with PR
|
0 Participants
|
|
Overall Response Based on Tumor Volume Score (TVS)
Subjects with SD
|
3 Participants
|
SECONDARY outcome
Timeframe: week 12Population: Modified intent-to-treat, 3 subjects with ROM data in right and left knee were analyzed
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.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=3 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Mean Change From Baseline Range of Motion (ROM) (Flexion, Knee) Scores
Subjects with no change in ROM from baseline
|
1 Participants
|
|
Mean Change From Baseline Range of Motion (ROM) (Flexion, Knee) Scores
Subjects with change in ROM Left Knee
|
1 Participants
|
|
Mean Change From Baseline Range of Motion (ROM) (Flexion, Knee) Scores
Subjects with change in ROM Right Knee
|
1 Participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Subjects with TGCT
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
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=3 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Mean Change From Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Score
|
0 score on a scale
Standard Deviation 2.65
|
SECONDARY outcome
Timeframe: 10 weeksPopulation: All enrolled subjects
The maximum concentration of AMB-05X in subject serum is measured at week 10 postdose, using sensitive enzyme-linked immunosorbent assay analyses (ELISA).
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=4 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Serum Cmax for AMB-05X at Week 10 Post Dose
|
54,457 ng/mL
Standard Deviation 30,356
|
SECONDARY outcome
Timeframe: 10 weeksPopulation: All enrolled subjects
AMB-05X Anti-drug Antibodies (ADA) in subject serum will be measured from pre-dose samples.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=4 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Number of Subjects With Anti-Drug Antibodies to AMB-05X at Week 10
Subjects ADA positive at any visit analyzed
|
1 Participants
|
|
Number of Subjects With Anti-Drug Antibodies to AMB-05X at Week 10
Subjects ADA negative at every visit analyzed
|
3 Participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: TGCT subjects
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.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=3 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Mean Change From Baseline in Worst Stiffness Numeric Rating Scale (NRS) Score
|
-2.7 score on a scale
Standard Deviation 2.52
|
SECONDARY outcome
Timeframe: 12 weeksThe 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.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=3 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Brief Pain Inventory Pain Severity Domain Score
|
-0.83 score on a scale
Standard Deviation 1.665
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: TGCT subjects
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.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=3 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Mean Change From Baseline in Brief Pain Inventory Severity Interference
|
0.81 score on a scale
Standard Deviation 1.528
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: TGCT subjects
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.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=3 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Worst Pain Numeric Rating Scale Score
|
-0.3 score on a scale
Standard Deviation 1.53
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: TGCT subjects
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.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=3 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
EuroQol 5 Dimension 5 Level Health Assessment
|
-0.3 score on a scale
Standard Deviation 0.58
|
SECONDARY outcome
Timeframe: 10 weeksPopulation: TGCT subjects
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.
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=3 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Colony-stimulating Factor 1 Levels
|
1216 pg/mL
Standard Deviation 372
|
SECONDARY outcome
Timeframe: week 12Population: Although the protocol allowed patients with TGCT of the ankle, no subjects with TGCT of the ankle were enrolled.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 12Population: Measurement of serum AMB-05X-Binding anti-drug antibody (ADA) levels was a prespecified secondary outcome measure. ADA data for 4 subjects enrolled prior to study termination are provided. One of 4 subjects provided only a baseline sample. Three of 4 subjects provided both baseline (Visit 2) and Week 10 (Visit 7) samples. No conclusions were made based on the limited information collected at study termination (Sponsor stopped developing intravenous AMB-05X for patients with TGCT).
Series analysis for anti-drug antibody detection and titer
Outcome measures
| Measure |
Cohort A: Subjects With TGCT
n=4 Participants
AMB-05X Each subject will receive a 4mg/kg and maintenance dose of 2 mg/kg AMB-05X every 2 weeks, for a total of 6 doses over the 12-week treatment period.
AMB-05X: A fully human monoclonal immunoglobulin (IgG2) directed against c-fms
|
|---|---|
|
Serum AMB-05X-Binding Anti-drug Antibody (ADA) Levels
Baseline visit · Subjects ADA negative
|
3 Participants
|
|
Serum AMB-05X-Binding Anti-drug Antibody (ADA) Levels
Baseline visit · Subjects ADA positive
|
1 Participants
|
|
Serum AMB-05X-Binding Anti-drug Antibody (ADA) Levels
Visit 7 · Subjects ADA negative
|
2 Participants
|
|
Serum AMB-05X-Binding Anti-drug Antibody (ADA) Levels
Visit 7 · Subjects ADA positive
|
1 Participants
|
Adverse Events
Tenosynovial Giant Cell Tumor - Events During Initial Treatment Period
Tenosynovial Giant Cell Tumor - Events During Maintenance Treatment Period
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Tenosynovial Giant Cell Tumor - Events During Initial Treatment Period
n=4 participants at risk
Cohort A: Received initial priming dose on Day 1 followed by 5 maintenance doses administered every 2 weeks (at Weeks 2, 4, 6, 8, and 10), for a total of 6 doses over the 12-week treatment period.
|
Tenosynovial Giant Cell Tumor - Events During Maintenance Treatment Period
n=4 participants at risk
Cohort A: Received initial priming dose on Day 1 followed by 5 maintenance doses administered every 2 weeks (at Weeks 2, 4, 6, 8, and 10), for a total of 6 doses over the 12-week treatment period.
|
|---|---|---|
|
General disorders
face edema
|
0.00%
0/4 • 6 months
|
100.0%
4/4 • 6 months
|
|
Investigations
hepatic enzyme increased
|
0.00%
0/4 • 6 months
|
25.0%
1/4 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
0.00%
0/4 • 6 months
|
25.0%
1/4 • 6 months
|
|
Vascular disorders
hypertension
|
0.00%
0/4 • 6 months
|
25.0%
1/4 • 6 months
|
|
Nervous system disorders
headache
|
0.00%
0/4 • 6 months
|
25.0%
1/4 • 6 months
|
|
Skin and subcutaneous tissue disorders
rash maculopapular
|
0.00%
0/4 • 6 months
|
25.0%
1/4 • 6 months
|
|
Skin and subcutaneous tissue disorders
skin hyperpigmentation
|
0.00%
0/4 • 6 months
|
25.0%
1/4 • 6 months
|
|
Investigations
blood lactate dehydrogenase increased
|
0.00%
0/4 • 6 months
|
50.0%
2/4 • 6 months
|
|
Gastrointestinal disorders
diarrhea
|
0.00%
0/4 • 6 months
|
25.0%
1/4 • 6 months
|
|
Investigations
aspartate aminotransferase increased
|
0.00%
0/4 • 6 months
|
25.0%
1/4 • 6 months
|
|
Infections and infestations
pyelonephritis acute
|
0.00%
0/4 • 6 months
|
25.0%
1/4 • 6 months
|
|
Infections and infestations
urinary tract infection
|
0.00%
0/4 • 6 months
|
25.0%
1/4 • 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER