Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT)

Phase 3

Recruiting

• Conditions: TGCT
• Interventions: Drug: Emactuzumab; Drug: Placebo

• Registration Number: NCT05417789
• Lead Sponsor: SynOx Therapeutics Limited

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, subject to eligibility, to crossover 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-06-01
• Study First Submitted QC: 2022-06-08
• Study First Posted: 2022-06-14
• Study Start: 2024-04-30
• Status Verified: 2024-10
• Last Update Submitted: 2024-12-16
• Last Update Posted: 2024-12-17
• Primary Completion: 2026-04-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 128

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.
• Measurable disease: longest diameter ≥20 mm.
• 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

Read More

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 systemic therapy for TGCT (investigational or approved) targeting CSF-1 or CSF-1R or any multi-tyrosine kinase inhibitor (eg nilotinib and imatinib) within 3 months prior to screening
• Any surgery, chemotherapy or radiotherapy within 3 months of screening
• 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) including severe thromboembolic event; incompletely healed clinically significant wounds, including bone fractures; pathological fracture or significant hypercalcaemia.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 in Part 1/Part 2: Emactuzumab	Emactuzumab	Group 1: Subjects receiving emactuzumab administered intravenously (i.v) 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. Eligible Subjects assigned to active drug in Part 1 have the option to receive open-label retreatment in Part 2.
Group 2 in Part 1 and Part 2: Placebo	Placebo	Group 2: Subjects receiving placebo administered intravenously (i.v) 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. In Part 2, Eligible Subjects will have the option to receive open-label emactuzumab, administered by i.v once every 2 weeks (Q2W) for a total of 5 times.

Primary Outcome Measures

Name	Time	Method
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 according to RECIST v1.1 based on independent, blinded central review

Secondary Outcome Measures

Name	Time	Method
Tumour volume score (TVS)	up to 24 months	Change in Tumour volume score (TVS)
Surgical Intervention Rate	up to 24 months	The number of subjects who undergo surgery during the study for TGCT
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
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

Trial Locations

Locations (29)

Sarcoma Oncology Research Center, LLC; 🇺🇸 Los Angeles, California, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Cliniques Universitaires Saint-Luc; 🇧🇪 Woluwe-Saint-Lambert, Brussels, Belgium

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

McGill University Health Centre (MUHC); 🇨🇦 Montreal, Quebec, Canada

Centre Antoine Lacassagne; 🇫🇷 Nice, Alpes-Maritimes, France

Institut Bergonie - PPDS; 🇫🇷 Bordeaux, Gironde, France

Institut de Cancerologie de Ouest - Saint Herblain; 🇫🇷 Saint-Herblain, Loire-Atlantique, France

Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes; 🇫🇷 Lyon, Rhône, France

UNICANCER - Centre Oscar Lambret; 🇫🇷 Lille, France

AP-HP - Hôpital Cochin - Port-Royal, site Cochin; 🇫🇷 Paris, France

Fondazione Policlinico Universitario Campus Bio-Medico; 🇮🇹 Roma, Lazio, Italy

Fondazione del Piemonte per l'Oncologia (IRCCS); 🇮🇹 Candiolo, Piemonte, Italy

Nuovo Ospedale di Prato; 🇮🇹 Prato, Toscana, Italy

Hospital Clinico San Carlos; 🇪🇸 Madrid, Madrin, Spain

Hospital Universitario Fundacion Jimenez Diaz; 🇪🇸 Zaragoza, Spain

Skanes Universitetssjukhus Lund; 🇸🇪 Lund, Skane lan, Sweden

Universitäts Kinderspital Beider Basel (UKBB); 🇨🇭 Basel, Switzerland

Inselspital - Universitätsspital Bern; 🇨🇭 Bern, Switzerland

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

University College Hospital; 🇬🇧 London, United Kingdom

MedStar Washington Hospital Center; 🇺🇸 Georgetown, Washington, United States

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone; 🇮🇹 Palermo, Sicily, Italy

Azienda Ospedaliero Universitaria Pisana - Stabilimento di Cisanello; 🇮🇹 Pisa, Italy

IRCCS lstituto Ortopedico Rizzoli; 🇮🇹 Bologna, Italy

Leids Universitair Medisch Centrum; 🇳🇱 Leiden, Netherlands

Hospital de La Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan