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    Summary
    EudraCT Number:2021-001716-29
    Sponsor's Protocol Code Number:SNX-301-020
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2022-06-02
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2021-001716-29
    A.3Full title of the trial
    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.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Trial to Assess the Safety and Efficacy of Emactuzumab versus Placebo in Patients with Giant Cell Tumours.
    A.3.2Name or abbreviated title of the trial where available
    TANGENT
    A.4.1Sponsor's protocol code numberSNX-301-020
    A.5.4Other Identifiers
    Name:INDNumber:153633
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSynOx Therapeutics Ltd
    B.1.3.4CountryIreland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportSynOx Therapeutics Ltd
    B.4.2CountryIreland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSynOx Therapeutics Ltd
    B.5.2Functional name of contact pointRowena Abbey
    B.5.3 Address:
    B.5.3.1Street Address25-28 North Wall Quay
    B.5.3.2Town/ cityDublin
    B.5.3.3Post codeD01 H104
    B.5.3.4CountryIreland
    B.5.4Telephone number+447789626678
    B.5.6E-mailRowena.Abbey@synoxtherapeutics.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEmactuzumab (RO5509554)
    D.3.2Product code RO5509554
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEMACTUZUMAB
    D.3.9.2Current sponsor codeRO5509554, RG7155
    D.3.9.3Other descriptive nameRO5509554, RG7155
    D.3.9.4EV Substance CodeSUB177212
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboConcentrate and solvent for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Tenosynovial Giant Cell Tumour
    E.1.1.1Medical condition in easily understood language
    Giant Cell Tumours
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10025564
    E.1.2Term Malignant giant cell tumor
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To estimate the treatment effect of emactuzumab on objective response rate (ORR) by 6 months from initiation of therapy in the blinded phase compared to placebo.
    E.2.2Secondary objectives of the trial
    -To estimate:
    The effect of emactuzumab on clinical outcome assessments (COAs) for:

    o Physical functioning
    o Range of motion (ROM)
    o Pain
    o Stiffness
    o Patient Global Impressions (PGIs)
    o QoL

    -Further antitumour activity of emactuzumab in TGCT compared to placebo.

    -Surgical Intervention Rate.

    -The Safety Objective of this study is to monitor subject wellbeing and assess treatment tolerability .

    -To assess the health economic impact of treatment with emactuzumab.

    -To further characterize the pharmacokinetic (PK) profile of emactuzumab.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent.
    2. Biopsy-confirmed (standard of care diagnosis history) local or diffuse TGCT where surgical resection would be associated with predicted worsening functional limitations due to surgical damage to the joint and adjacent soft tissues, and/or subject presents with
    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.
    *The multidisciplinary tumour board or equivalent must comprise at least 2 individuals:
    the Investigator plus at least one other qualified physician (orthopaedic surgeon or
    medical oncologist) not involved in this study.
    3. Measurable disease: longest diameter ≥20 mm.
    4. Age >12 years.
    5. Adequate organ and bone marrow function: haemoglobin (Hb) >10.0 g/dL,
    neutrophils >1.5 × 109/L and platelets >100 × 109/L.
    6. Minimum mean score of 4 on NRS for Worst Pain during 7 days prior to randomization,
    based upon a minimum of 4 days of completed diary data.
    7. Minimum mean score of 4 on NRS for Worst Stiffness during 7 days prior to
    randomization, based upon a minimum of 4 days of completed diary data.
    8. Women of childbearing potential (WOCBP) must have a negative urine and serum pregnancy test prior to starting treatment. WOCBP must agree to use a highly effective method of contraception throughout the treatment period and for 7 months after
    discontinuation of treatment. Acceptable methods of contraception according to protocol description.
    9. For Open-Label Phase ONLY:
    Subjects must either:
    -Have responded based on RECIST v1.1 (CR or PR) to initial treatment with emactuzumab during the Double-Blind Phase and then progressed (objective progressive disease on imaging) within 9-18 months of initial treatment on D 1 (Visit 1) with a minimum 6-month washout period between treatments; or
    -Have received placebo and completed the 6-month visit on D 181/Visit 10
    (3 months treatment and 3 months observation) of the Double-Blind Phase and
    have not completed more than 18 months of the study since initial treatment on D1 (Visit1).
    E.4Principal exclusion criteria
    1. Pregnant or breast feeding.
    2. 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. All Lupus Erythematosus are excluded
    irrespective of treatment.
    3. Metastatic TGCT.
    4. TGCT currently affecting multiple joints.
    5. Pexidartinib therapy within 3 months of Screening.
    6. Nilotinib, imatinib; other chemotherapy, radiotherapy, or investigational therapy within 4
    weeks of Screening.
    7. Unresolved clinically significant toxicity from a previous treatment or any history of
    serious liver toxicity.
    8. Current or chronic history of liver disease. This includes, but is not limited to, hepatitis
    virus infections, drug- or alcohol-related liver disease, nonalcoholic steatohepatitis,
    autoimmune hepatitis, haemochromatosis, Wilson’s disease, α-1 antitrypsin deficiency,
    primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease
    which in the opinion of the Investigator is considered clinically significant.
    9. Renal function: creatinine clearance <60 mL/min (Cockcroft-Gault formula).
    10. Liver function: ALT >3.0 × ULN; OR total bilirubin >1.5 × ULN.
    11. 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).
    12. Clinically significant active infection requiring systemic antibiotic treatment.
    Rescreening may occur any time after 7 days post completion of treatment.
    13. Systemic antiretroviral therapy within 3 months of baseline.
    14. Other active cancer that requires concurrent treatment or history of malignancy other than
    TGCT, unless there is the expectation that the malignancy has been cured, and tumor
    specific treatment for the malignancy has not been administered within the previous
    5 years.
    15. Planned surgery during the course of the study with the exception of dental treatment.
    16. Inability to comply with the study procedures.
    17. For the Double-Blind Phase ONLY:
    Previous exposure to emactuzumab and/or neutralizing antibodies.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy objective of this study is to estimate the treatment effect of emactuzumab on objective response rate (ORR) by 6 months from initiation of therapy in the blinded phase compared to placebo.
    E.5.1.1Timepoint(s) of evaluation of this end point
    ORR by 6 months from initiation of therapy based on independent, blinded central review.
    E.5.2Secondary end point(s)
    Change in Patient-Reported Outcomes Measurement Information System-Physical Function
    (PROMIS-PF) TGCT from baseline to 6 months.

    Other secondary endpoints:
    -Change in PROMIS-PF TGCT from baseline over time.
    -Physician/Healthcare Professional (HCP)-Reported Joint Mobility Score by goniometry from baseline over time.
    -Change in Worst Pain Numerical Rating Scale (NRS) from baseline over time.
    -Change in Short Form 12-Item Survey version 2 (SF-12 v2) from baseline over time.
    -Change in Worst Stiffness NRS from baseline over time.
    -PGI of change and severity over time.
    -Change in EuroQol 5-dimension, 5-level questionnaire (EQ-5D-5L) from baseline over time.
    -Duration of response (DoR) as measured by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 based on independent, blinded central review.
    -Disease control rate (DCR) as measured by RECIST v1.1 based on independent, blinded central review
    -Time to progression as measured by RECIST v1.1 based on independent, blinded central review.
    -Change in Tumour volume score (TVS) from baseline over time.
    -Surgical intervention rate, defined as the number of subjects who undergo surgery for TGCT during the study.
    -AEs.
    -Deaths.
    -Any laboratory abnormalities.
    E.5.2.1Timepoint(s) of evaluation of this end point
    From baseline over time.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA45
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United States
    Austria
    France
    Poland
    Sweden
    Netherlands
    Spain
    Switzerland
    Germany
    Italy
    Belgium
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as the date of the last visit of the last subject in the study.
    A subject is considered to have completed the study if he/she has completed all periods of the
    study including the last visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days6
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 3
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 3
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 150
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 7
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Minors from 12 to 17 years old
    F.4 Planned number of subjects to be included
    F.4.1In the member state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 160
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-09-14
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2022-09-20
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