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

Sponsor

SynOx Therapeutics Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05417789

Collaborator

(none)

128

Enrollment

Locations

Arms

38.4

Anticipated Duration (Months)

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
TGCT	Drug: Emactuzumab Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

128 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jul 18, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Sep 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 in Part 1/Part 2: Emactuzumab 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.	Drug: Emactuzumab Emactuzumab administered once every 2 weeks (q2w)
Placebo Comparator: Group 2 in Part 1 and Part 2: Placebo 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.	Drug: Placebo Matching placebo administered once every 2 weeks (q2w)

Arm

Intervention/Treatment

Experimental: Group 1 in Part 1/Part 2: Emactuzumab

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.

Drug: Emactuzumab

Emactuzumab administered once every 2 weeks (q2w)

Placebo Comparator: Group 2 in Part 1 and Part 2: Placebo

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.

Drug: Placebo

Matching placebo administered once every 2 weeks (q2w)

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [Day 0 - Day 180 (6 months)]
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 [up to 24 months]
Change in Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) TGCT from baseline to 6 months
Range of Motion (ROM) [up to 24 months]
Mean change from baseline in active ROM of the joint over time
Worst Stiffness [up to 24 months]
Mean change from baseline in the Worst Stiffness Numeric Rating Scale (NRS) score over time
Worst Pain [up to 24 months]
Mean change in Pain Numerical Rating Scale (NRS) from baseline over time
Quality of Life (QoL) [up to 24 months]
Change in EuroQol 5-dimension, 5-level questionnaire (EQ-5D-5L)
Duration of response (DoR) [up to 24 months]
Duration of response (DoR) as measured by RECIST version 1.1
Tumour volume score (TVS) [up to 24 months]
Change in Tumour volume score (TVS)

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medstar Washington Hospital Center	Washington	District of Columbia	United States	20010-3017
2	Medstart Heart and Vascular Institute	Baltimore	Maryland	United States	21237