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Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT) (TANGENT)

Primary Purpose

TGCT

Status
Active
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Emactuzumab
Placebo
Sponsored by
SynOx Therapeutics Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for TGCT focused on measuring TGCT, Tenosynovial Giant Cell Tumour, PVNS, Pigmented Villonodular Synovitis, Synovitis, Emactuzumab, Local TGCT, Diffuse TGCT

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age >12 years
  • Biopsy-confirmed (standard of care diagnosis history) local or diffuse TGCT where surgical resection would be associated with predicted worsening functional limitations through surgical joint damage, and/or subject has an anticipated high risk of early recurrence as determined by a multidisciplinary tumour board or equivalent, or any other morbidity associated with the surgery, and/or surgical treatment is not expected to improve the clinical outcomes of the subject.
  • Adequate organ and bone marrow function
  • If a woman of childbearing potential (WOCBP), must have a negative pregnancy test prior to starting treatment and agree to use a highly effective method of contraception
  • Participants must have written consent

Exclusion Criteria:

  • If a female, the subject is pregnant or breast feeding.
  • Medical conditions, including auto-immune, requiring systemic immunosuppression. Any systemic treatment for these conditions (eg, glucocorticoids) is not allowed within 4 weeks of Screening and during the study.
  • Known metastatic TGCT or other active cancer that requires concurrent or planned treatment
  • Received therapy for TGCT within 4 weeks prior to screening and 3 months prior to screening for pexidartinib
  • Unresolved clinically significant toxicity from a previous treatment or any history of serious liver toxicity.
  • Current or chronic history of liver disease.
  • Inadequate renal and liver function
  • Systemic antiretroviral therapy within 3 months of baseline
  • Within 6 months of baseline has experienced: clinically significant myocardial infarction, severe/unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) Class III or IV, or pulmonary disease (NYHA Criteria 1994)

Sites / Locations

  • Medstar Washington Hospital Center
  • Medstart Heart and Vascular Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Group 1 in Part 1/Part 2: Emactuzumab

Group 2 in Part 1 and Part 2: Placebo

Arm Description

Group 1: Subjects receiving emactuzumab administered on Day(D)1 and repeated once every two weeks (Q2W) for a total of 5 times, followed by an observation period of 3 months leading to a total period of 24 weeks in Part 1 and continued with a follow-up phase in Part 2.

Group 2: Subjects receiving placebo administered as iv infusion on D1 and repeated once every two weeks (Q2W) for 5 times followed by an observation period of 3 months to a total period of 24 weeks in Part 1 will have the option to crossover under certain circumstances to open-label emactuzumab once every 2 weeks (Q2W) for a total of 5 times in Part 2.

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)
Objective Response Rate (ORR = complete response [CR] + partial response [PR]) by 6 months from initiation of therapy assessed by central read using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

Secondary Outcome Measures

Physical Function
Change in Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) TGCT from baseline to 6 months
Range of Motion (ROM)
Mean change from baseline in active ROM of the joint over time
Worst Stiffness
Mean change from baseline in the Worst Stiffness Numeric Rating Scale (NRS) score over time
Worst Pain
Mean change in Pain Numerical Rating Scale (NRS) from baseline over time
Quality of Life (QoL)
Change in EuroQol 5-dimension, 5-level questionnaire (EQ-5D-5L)
Duration of response (DoR)
Duration of response (DoR) as measured by RECIST version 1.1
Tumour volume score (TVS)
Change in Tumour volume score (TVS)

Full Information

First Posted
June 1, 2022
Last Updated
September 23, 2022
Sponsor
SynOx Therapeutics Limited
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1. Study Identification

Unique Protocol Identification Number
NCT05417789
Brief Title
Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT)
Acronym
TANGENT
Official Title
A Phase 3, Randomized, Placebo-controlled, Double-Blind Study of Emactuzumab to Assess Efficacy and Safety in Subjects With Tenosynovial Giant Cell Tumor (TANGENT)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 18, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
September 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SynOx Therapeutics Limited

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
This is a multicenter, Phase 3, randomised, double-blind, placebo-controlled study, which aims to evaluate the efficacy and safety of the investigational drug emactuzumab for the treatment of patients with localized or diffuse TGCT where surgical removal of the tumor is not viewed as an option. The study consists of two parts. In Part 1, eligible subjects will be assigned in a 2:1 ratio to receive either emactuzumab or matching placebo in a double-blind fashion, that will be administered in total 5 times as an intravenous (i.v.) infusion once every 2 weeks. This will be followed by an observation period of 3 months leading to a total duration of 24 weeks in Part 1. A number of assessments will be carried out during the course of the study, including physical examinations, blood tests, imaging studies, electrocardiograms, and questionnaires. Part 2 is a long-term double-blind follow-up phase of the subjects on emactuzumab or placebo. Subjects assigned to placebo in Part 1 have the option to crossover under certain circumstances to receive open-label emactuzumab in Part 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
TGCT
Keywords
TGCT, Tenosynovial Giant Cell Tumour, PVNS, Pigmented Villonodular Synovitis, Synovitis, Emactuzumab, Local TGCT, Diffuse TGCT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
128 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1 in Part 1/Part 2: Emactuzumab
Arm Type
Experimental
Arm Description
Group 1: Subjects receiving emactuzumab administered on Day(D)1 and repeated once every two weeks (Q2W) for a total of 5 times, followed by an observation period of 3 months leading to a total period of 24 weeks in Part 1 and continued with a follow-up phase in Part 2.
Arm Title
Group 2 in Part 1 and Part 2: Placebo
Arm Type
Placebo Comparator
Arm Description
Group 2: Subjects receiving placebo administered as iv infusion on D1 and repeated once every two weeks (Q2W) for 5 times followed by an observation period of 3 months to a total period of 24 weeks in Part 1 will have the option to crossover under certain circumstances to open-label emactuzumab once every 2 weeks (Q2W) for a total of 5 times in Part 2.
Intervention Type
Drug
Intervention Name(s)
Emactuzumab
Intervention Description
Emactuzumab administered once every 2 weeks (q2w)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo administered once every 2 weeks (q2w)
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Objective Response Rate (ORR = complete response [CR] + partial response [PR]) by 6 months from initiation of therapy assessed by central read using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Time Frame
Day 0 - Day 180 (6 months)
Secondary Outcome Measure Information:
Title
Physical Function
Description
Change in Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) TGCT from baseline to 6 months
Time Frame
up to 24 months
Title
Range of Motion (ROM)
Description
Mean change from baseline in active ROM of the joint over time
Time Frame
up to 24 months
Title
Worst Stiffness
Description
Mean change from baseline in the Worst Stiffness Numeric Rating Scale (NRS) score over time
Time Frame
up to 24 months
Title
Worst Pain
Description
Mean change in Pain Numerical Rating Scale (NRS) from baseline over time
Time Frame
up to 24 months
Title
Quality of Life (QoL)
Description
Change in EuroQol 5-dimension, 5-level questionnaire (EQ-5D-5L)
Time Frame
up to 24 months
Title
Duration of response (DoR)
Description
Duration of response (DoR) as measured by RECIST version 1.1
Time Frame
up to 24 months
Title
Tumour volume score (TVS)
Description
Change in Tumour volume score (TVS)
Time Frame
up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age >12 years Biopsy-confirmed (standard of care diagnosis history) local or diffuse TGCT where surgical resection would be associated with predicted worsening functional limitations through surgical joint damage, and/or subject has an anticipated high risk of early recurrence as determined by a multidisciplinary tumour board or equivalent, or any other morbidity associated with the surgery, and/or surgical treatment is not expected to improve the clinical outcomes of the subject. Adequate organ and bone marrow function If a woman of childbearing potential (WOCBP), must have a negative pregnancy test prior to starting treatment and agree to use a highly effective method of contraception Participants must have written consent Exclusion Criteria: If a female, the subject is pregnant or breast feeding. Medical conditions, including auto-immune, requiring systemic immunosuppression. Any systemic treatment for these conditions (eg, glucocorticoids) is not allowed within 4 weeks of Screening and during the study. Known metastatic TGCT or other active cancer that requires concurrent or planned treatment Received therapy for TGCT within 4 weeks prior to screening and 3 months prior to screening for pexidartinib Unresolved clinically significant toxicity from a previous treatment or any history of serious liver toxicity. Current or chronic history of liver disease. Inadequate renal and liver function Systemic antiretroviral therapy within 3 months of baseline Within 6 months of baseline has experienced: clinically significant myocardial infarction, severe/unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) Class III or IV, or pulmonary disease (NYHA Criteria 1994)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean Y Blay, Prof, MD
Organizational Affiliation
Comprehensive Cancer Centre of Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medstar Washington Hospital Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010-3017
Country
United States
Facility Name
Medstart Heart and Vascular Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21237
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Summary (synopsis) of the CSR

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Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT)

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