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

A Phase III, Multicentre, Randomised, Double-Blind Study to Assess the Safety and Efficacy of Emactuzumab vs. Placebo in Subjects With Tenosynovial Giant Cell Tumour

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. Subjects assigned to active drug in Part 1 have the option to receive open-label retreatment under certain circumstances.

Study Overview

• Status: Not yet recruiting
• Conditions: TGCT
• Intervention / Treatment: Drug: Emactuzumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Team Synox; Phone Number: +44 1865 338097; Email: clinicaltrials@synoxtherapeutics.com

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-3017
      • MedStar Washington Hospital Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Medstart Heart and Vascular Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 given 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)
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. Subjects assigned to active drug in Part 1 have the option to receive open-label retreatment under certain circumstances	Drug: Emactuzumab; Emactuzumab administered once every 2 weeks (q2w)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Objective Response Rate (ORR = complete response [CR] + partial response [PR]) by 6 months from initiation of therapy according to RECIST v1.1 based on independent, blinded central review	Day 0 - Day 180 (6 months)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: SynOx Therapeutics Limited
• Investigators: Principal Investigator: Jean Y Blay, Prof, MD, Comprehensive Cancer Centre of Lyon

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Synovitis; TGCT, Tenosynovial Giant Cell Tumour; PVNS, Pigmented Villonodular Synovitis; Emactuzumab; Local TGCT; Diffuse TGCT
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Neoplasms, Connective Tissue; Tendinopathy; Synovitis; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath
• Other Study ID Numbers: SNX-301-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Summary (synopsis) of the CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No