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

• ClinicalTrials.gov Identifier: NCT05417789
• Recruitment Status: Active, not recruiting
• First Posted: June 14, 2022
• Last Update Posted: September 26, 2022
• Sponsor: SynOx Therapeutics Limited
• Information provided by (Responsible Party): SynOx Therapeutics Limited

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 (Clinical Trial)
• Actual 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: July 18, 2022
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: September 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)

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: 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 :

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

Eligibility Criteria

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

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)

Contacts and Locations

Locations

United States, District of Columbia

Medstar Washington Hospital Center

Washington, District of Columbia, United States, 20010-3017

United States, Maryland

Medstart Heart and Vascular Institute

Baltimore, Maryland, United States, 21237

Sponsors and Collaborators

SynOx Therapeutics Limited

Investigators

• Principal Investigator: Jean Y Blay, Prof, MD; Comprehensive Cancer Centre of Lyon

More Information

• Responsible Party: SynOx Therapeutics Limited
• ClinicalTrials.gov Identifier: NCT05417789
• Other Study ID Numbers: SNX-301-02
• First Posted: June 14, 2022
• Last Update Posted: September 26, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by SynOx Therapeutics Limited:

TGCT, Tenosynovial Giant Cell Tumour; PVNS, Pigmented Villonodular Synovitis; Synovitis; Emactuzumab; Local TGCT; Diffuse TGCT

Additional relevant MeSH terms:

Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Synovitis; Joint Diseases; Musculoskeletal Diseases; Tendinopathy; Muscular Diseases