TGCTPhase 3TANGENTNCT05417789
Study of Emactuzumab for Tenosynovial Giant Cell Tumor (TGCT)
A Phase 3 study testing Emactuzumab in people with TGCT, run by SynOx Therapeutics Limited at 33 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- TGCT
- What is being tested?
- Emactuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 128 participants
- Where
- 33 sitesin 12 countries
- Study dates
- 9 Oct 2024to 30 Sep 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
33 sites in 12 countries.
33 sites in 12 countries
France7 sites
Institut Bergonie - PPDS
Bordeaux, Gironde, 33000
UNICANCER - Centre Oscar Lambret
Lille, 59000
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
Lyon, Rhône, 69373
AP-HP - Hôpital Cochin - Port-Royal, site Cochin
Paris, Paris, 75014
Institut Curie - Hôpital de Paris
Paris, 75248
Institut de Cancerologie de Ouest - Saint Herblain
Saint-Herblain, Loire-Atlantique, 44115
Oncopole Claudius Regaud Oncologie Médicale
Toulouse, 31059
Italy6 sites
IRCCS lstituto Ortopedico Rizzoli
Bologna, 40136
Fondazione del Piemonte per l'Oncologia (IRCCS)
Candiolo, Piedmont, 10060
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Palermo, Sicily, 90127
Fondazione Policlinico Universitario Campus Bio-Medico
Rome, Lazio, 00128
Istituti Fisioterapici Ospitalieri - IRCCS Istituto Nazionale Tumori Regina Elena
Rome, Lazio, 00144
United States5 sites
NextGen Oncology
Beverly Hills, California, 90212
The Ohio State University
Columbus, Ohio, 43201
MedStar Washington Hospital Center
Georgetown, Washington, 20010
MD Anderson Cancer Center
Houston, Texas, 77030
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90089
Spain4 sites
Hospital de La Santa Creu i Sant Pau
Barcelona, 8041
Hospital Universitario Virgen del Rocio - PPDS
Seville, 41013
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Hospital Universitario Fundacion Jimenez Diaz
Zaragoza, Zaragoza, 50009
Canada3 sites
Arthur J.E. Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 4N1
McGill University Health Centre (MUHC)
Montreal, Quebec, H1T 2M4
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
United Kingdom2 sites
St James's University Hospital
Leeds, LS9 7TF
University College Hospital
London, NW1 2BU
Belgium1 site
Cliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert, Brussels Capital, 1200
Switzerland1 site
Universitäts Kinderspital Beider Basel (UKBB)
Basel, 4031
About this study
Official title: 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, 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.
- Conditions
- TGCT
- Being tested
- Emactuzumab, Placebo
- Keywords
- TGCT, Tenosynovial Giant Cell Tumour, PVNS, Pigmented Villonodular Synovitis, Synovitis, Emactuzumab, Local TGCT, Diffuse TGCT
- Medical subject headings
- Synovitis, Pigmented Villonodular, Synovitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmactuzumabDrug
Emactuzumab administered once every 2 weeks (q2w)
PlaceboDrug
Matching placebo administered once every 2 weeks (q2w)
| Study group | Role | What they receive |
|---|---|---|
| Group 1 in Part 1/Part 2: Emactuzumab | Experimental | 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. Receives: Drug: Emactuzumab |
| Group 2 in Part 1 and Part 2: Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day 0 - Day 180 (6 months)
Secondary outcomes (8)
Physical Function
Change in Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) TGCT from baseline to 6 months
Measured: up to 24 months
Range of Motion (ROM)
Mean change from baseline in active ROM of the joint over time
Measured: up to 24 months
Worst Stiffness
Mean change from baseline in the Worst Stiffness Numeric Rating Scale (NRS) score over time
Measured: up to 24 months
Worst Pain
Mean change in Pain Numerical Rating Scale (NRS) from baseline over time
Measured: up to 24 months
Quality of Life (QoL)
Change in EuroQol 5-dimension, 5-level questionnaire (EQ-5D-5L)
Measured: up to 24 months
Duration of response (DoR)
Duration of response (DoR) as measured by RECIST version 1.1
Measured: up to 24 months
Tumour volume score (TVS)
Change in Tumour volume score (TVS)
Measured: up to 24 months
Surgical Intervention Rate
The number of subjects who undergo surgery during the study for TGCT
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2022
- Study start9 Oct 2024
- Primary completion23 Dec 2025
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TGCTStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 128 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SynOx Therapeutics Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jean Y Blay, Prof, MD, Principal investigator, Comprehensive Cancer Centre of Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05417789
- Sponsor's protocol ID
- SNX-301-020
- Acronym
- TANGENT
- Status last verified
- Jul 2026
- First submitted
- 1 Jun 2022
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Summary (synopsis) of the CSR
Publications
Gelderblom H, Palmerini E, van de Sande M, Martin-Broto J, Tinoco G, Seltzer E, Davies M, Coll R, Veltkamp S, Blay JY. TANGENT study design: a phase III, randomized study of emactuzumab for the treatment of tenosynovial giant cell tumors. Future Oncol. 2026 Aug;22(18):2109-2119. doi: 10.1080/14796694.2026.2702768. Epub 2026 Jul 20.
PubMed 42473802
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05417789
- Acronym / sponsor ID
- TANGENT / SNX-301-020
- Conditions
- TGCT
- Keywords
- TGCT, Tenosynovial Giant Cell Tumour, PVNS, Pigmented Villonodular Synovitis, Synovitis, Emactuzumab, Local TGCT, Diffuse TGCT
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 128 participants (estimated)
- Lead sponsor
- SynOx Therapeutics LimitedIndustry (pharma, biotech, devices)
- Study start
- 9 Oct 2024 (actual)
- Primary completion
- 23 Dec 2025 (actual)
- Study completion
- 30 Sep 2030 (estimated)
- First posted
- 14 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 in Part 1/Part 2: Emactuzumab | Experimental | Drug: EmactuzumabGroup 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 comparator | Drug: PlaceboGroup 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. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EmactuzumabEmactuzumab administered once every 2 weeks (q2w) | Drug | Group 1 in Part 1/Part 2: Emactuzumab |
| PlaceboMatching placebo administered once every 2 weeks (q2w) | Drug | Group 2 in Part 1 and Part 2: Placebo |
Primary outcome
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 according to RECIST v1.1 based on independent, blinded central review
8 secondary outcomes
Physical Function
Time frame: up to 24 months
Range of Motion (ROM)
Time frame: up to 24 months
Worst Stiffness
Time frame: up to 24 months
Worst Pain
Time frame: up to 24 months
Quality of Life (QoL)
Time frame: up to 24 months
Duration of response (DoR)
Time frame: up to 24 months
Tumour volume score (TVS)
Time frame: up to 24 months
Surgical Intervention Rate
Time frame: up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2026.
- Derived from this study: PubMed 42473802Gelderblom H, Palmerini E, van de Sande M, Martin-Broto J, Tinoco G, Seltzer E, Davies M, Coll R, Veltkamp S, Blay JY. TANGENT study design: a phase III, randomized study of emactuzumab for the treatment of tenosynovial giant cell tumors. Future Oncol. 2026 Aug;22(18):2109-2119. doi: 10.1080/14796694.2026.2702768. Epub 2026 Jul 20.
- Individual participant dataSharing planned: No. Summary (synopsis) of the CSR
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean Y Blay, Prof, MD principal investigator
Comprehensive Cancer Centre of Lyon
33 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Emactuzumab in people with TGCT, run by SynOx Therapeutics Limited at 33 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in France, Italy, United States, Spain, Canada and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: Day 0 - Day 180 (6 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05417789, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026.