Back to results

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

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

NCT ID

NCT05417789

First Posted

June 1, 2022

Last Updated

September 23, 2022

Sponsor

SynOx Therapeutics Limited

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

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

Arm Title

Group 2 in Part 1 and Part 2: Placebo

Arm Type

Placebo Comparator

Arm Description

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

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

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

IPD Sharing Plan Description

Summary (synopsis) of the CSR

Learn more about this trial

Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT)

We'll reach out to this number within 24 hrs