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    Summary
    EudraCT Number:2015-000547-17
    Sponsor's Protocol Code Number:FPA008-002
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-07-20
    Trial results View 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 ConcernedFrance - ANSM
    A.2EudraCT number2015-000547-17
    A.3Full title of the trial
    A Phase 1/2 Study of FPA008, an anti-CSF1 Receptor Antibody, in Patients with Pigmented Villonodular Synovitis (PVNS)/ Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)
    Étude de phase 1/2 sur le FPA008, un anticorps anti-récepteur du CSF1 chez les patients atteints de synovite villonodulaire pigmentée (SVNP)/tumeur ténosynoviale à cellules géantes de type diffus (TTCG-td)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A trial to evaluate the safety and tolerability of FPA008 in a condition involving patients with joint disease (involving inflammation and overgrowth of the joint lining)
    A.3.2Name or abbreviated title of the trial where available
    Phase 1/2 of FPA008 in PVNS/dt-TGCT
    A.4.1Sponsor's protocol code numberFPA008-002
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorFive Prime Therapeutics, Inc.
    B.1.3.4CountryUnited States
    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 supportFive Prime Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationFive Prime Therapeutics, Inc.
    B.5.2Functional name of contact pointRobert Sikorski
    B.5.3 Address:
    B.5.3.1Street AddressTwo Corporate Drive
    B.5.3.2Town/ citySouth San Francisco
    B.5.3.3Post codeCA 94080-7047
    B.5.3.4CountryUnited States
    B.5.4Telephone number+14153655761
    B.5.5Fax number+14153655601
    B.5.6E-mailrobert.sikorski@fiveprime.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.3.2Product code FPA008
    D.3.4Pharmaceutical form 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 INNN/A
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeFPA008
    D.3.9.3Other descriptive nameHumanised IgG4 monoclonal antibody with high affinity binding to human colony stimulating factor 1 receptor
    D.3.9.4EV Substance CodeSUB33114
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pigmented villonodular synovitis (PVNS)/Diffuse Type Tenosynovial Giant Cell Tumor (dt-TGCT)
    E.1.1.1Medical condition in easily understood language
    Joint disease involving inflammation and overgrowth of the joint lining
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10047413
    E.1.2Term Villonodular synovitis
    E.1.2System Organ Class 100000004859
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Phase 1: to determine the recommended dose (RD) of FPA008 in patients with PVNS/dt-TGCT
    Phase 2: to estimate the objective response rate (ORR = Complete Response+Partial Response) of FPA008 in patients with PVNS/dt-TGCT
    Phase 1 : Déterminer la dose recommandée (DR) de FPA008 chez des patients atteints de synovite villonodulaire pigmentée (SVNP)/tumeur ténosynoviale à cellules géantes de type diffus (TTCG-td)
    Phase 2 : Estimer le taux de réponses objectives (TRO = RC+RP) du FPA008 chez les patients atteints de SVNP/TTCG-td
    E.2.2Secondary objectives of the trial
    to characterize the safety and tolerability of FPA008 in patients with PVNS/dt-TGCT
    to determine the duration of response in responding patients
    to assess the pharmacokinetics of FPA008 in patients with PVNS/dt-TGCT
    Caractériser la sécurité d'emploi et la tolérance de FPA008 chez les patients atteints de SVNP/TTCG-td
    Déterminer la durée de la réponse chez les patients auxquels il fait de l’effet
    Evaluer la pharmacocinétique du FPA008 chez les patients atteints de SVNP/TTCG-td
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Understand and sign an Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to any study-specific evaluation
    2. Age >=18 years
    3. Histologically confirmed diagnosis of inoperable PVNS/ dt-TGCT or potentially resectable tumor that would result in unacceptable functional loss or morbidity as determined by a qualified surgeon or multi-disciplinary tumor board (must be determined in the CRF during screening)
    4. Measurable PVNS/dt-TGCT by RECIST 1.1 on MRI
    5. ECOG performance status <=1
    6. Willing and able to comply with all study procedures
    7. In sexually-active patients (i.e., females of childbearing potential, who have not undergone menopause as defined by 12 consecutive months of amenorrhea or had a permanent sterilization procedure and males, who have not had a permanent sterilization procedure), willingness to use 2 effective methods of contraception, of which one must be a physical barrier method (condom, diaphragm, or cervical/vault cap) until 6 months after the last dose of FPA008. Other effective forms of contraception are permanent sterilization (hysterectomy and/or bilateral oophorectomy, or bilateral tubal ligation with surgery, or vasectomy) at least 6 months prior to Screening. Females <55 years of age should have FSH >40. Female patients of childbearing potential must be on stable oral contraceptive therapy or intrauterine or implant device for at least 90 days prior to the study, or abstain from sexual intercourse as a way of living.
    1. Comprendre et signer un formulaire de consentement éclairé validé par un comité de protection des personnes avant toute évaluation propre à l’étude.
    2. Âge ≥ 18 ans
    3. Diagnostic confirmé par un bilan histologique de SVNP/TTCG-td inopérable ou de tumeur potentiellement résécable qui donnerait lieu à une perte fonctionnelle ou à une morbidité inacceptable, telle que déterminée par un chirurgien qualifié ou une équipe pluridisciplinaire d’évaluation tumorale (ceci doit être documenté dans le cahier d’observation au cours de la phase de sélection).
    4. SVNP /TTCG-td mesurable par RECIST 1.1 sur IRM
    5. Indice de performance ECOG ≤1
    6. Patient disposé et apte à respecter toutes les procédures du protocole
    7. Chez les patients sexuellement actifs (c’est-à-dire les femmes en âge de procréer, qui ne sont pas en ménopause, définie par 12 mois consécutifs d’aménorrhée ou qui n’ont pas été stérilisées de façon définitive par intervention chirurgicale, et les hommes qui n’ont pas été stérilisés de façon définitive par intervention chirurgicale), être disposé à utiliser deux méthodes contraceptives efficaces, dont une doit être une méthode à barrière physique (préservatif, diaphragme vaginal) jusqu’à 6 mois après la prise de la dernière dose de FPA008. Les autres formes efficaces de contraception sont la stérilisation définitive (hystérectomie et/ou oophorectomie bilatérale, ou ligature bilatérale des trompes par intervention chirurgicale, ou vasectomie) au moins 6 mois avant la sélection. Les femmes < 55 ans doivent avoir une FSH > 40. Les patientes en âge de procréer doivent être sous traitement contraceptif oral stable ou sous stérilet ou implant contraceptif depuis au moins 90 jours au moment du début de l’étude, ou pratiquer l’abstinence sexuelle.

    E.4Principal exclusion criteria
    1. Prior therapy with an anti-CSF1R antibody
    2. Prior therapy with PLX3397 unless discontinued for intolerance (i.e., non-progression on prior kinase inhibitor); prior therapy with imatinib or nilotinib is allowed
    3. CK and liver function tests (including ALT, AST, and total bilirubin), outside of the range of local laboratory normal at Screening
    4. Inadequate organ or bone marrow function defined as: hemoglobin < 10 g/dL, absolute neutrophil count <1.5x 10x9/L, platelet count <100x 10x9/L, serum creatinine >1.5x ULN or calculated creatinine clearance <30 mL/min
    5. Any surgical procedure of the involved joint within 12 weeks prior to first study dose administration (except baseline synovium biopsy, if performed)
    6. Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels
    7. History of congestive heart failure or myocardial infarction <1 year prior to first study dose administration
    8. Decreased cardiac function with NYHA > Class 2
    9. Uncontrolled or significant heart disorder such as unstable angina
    10. Significant abnormalities on ECG at Screening. QTcF >450 msec for males or >470 msec for females at Screening
    11. Contraindications to MRI and use of intravenous gadolinium-based contrast agents
    12. History of severe allergic, anaphylactic, or other infusion related reaction to a previous biologic agent
    13. Treatment with any anticancer therapy or participation in another therapeutic clinical study with investigational drugs ≤ 28 days prior to first dose of FPA008
    14. Known history of ADAs to previous biologic agents
    15. Known history of sensitivity to Tween 20 (polysorbate 20)
    16. Consumption of non-pasteurized milk on a regular basis, or known significant risk of exposure to opportunistic intracellular infections such as listeria, or other such pathogens.
    17. Receipt of any vaccine within 28 days prior to first day of treatment. The effect of FPA008 on mounting an immunologic vaccine response is not known. Flu or other vaccinations may be administered while on study but the impact of FPA008 on the safety and efficacy of the vaccination is unknown.
    18. Current unresolved infection or history of chronic active clinically significant infection (viral [e.g., HBV, HCV], bacterial, fungal, or other), which in the opinion of the Investigator would place the patient at risk from exposure to a CSF1R inhibitor
    19. Known positive test for human immunodeficiency virus (HIV)
    20. Active TB
    21. Positive test for latent TB at Screening (Quantiferon test)
    22. History of prior malignancy, except:
    • Curatively treated non-melanoma skin malignancy
    • Cervical cancer in situ
    • Solid tumor treated curatively more than 2 years previously without evidence of recurrence
    23. Lack of peripheral venous access or any condition that would interfere with drug administration or collection of study samples
    24. Any uncontrolled medical condition or psychiatric disorder which in the opinion of the Investigator would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results
    25. Inability to perform and/or comply with study and follow-up procedures.
    1. Traitement antérieur par un anticorps anti-récepteur du CSF1
    2. Traitement antérieur par PLX3397, sauf s'il a été interrompu pour intolérance (c’est-à-dire non progression sous inhibiteur de kinases antérieur) ; un traitement antérieur par imatinib ou nilotinib est autorisé
    3. Dosages de CK et bilan hépatique (notamment ASAT, ALAT et bilirubine totale) en dehors de la plage des valeurs normales locales de laboratoire à la sélection
    4. Fonction organique ou médullaire insuffisante définie comme : hémoglobine <10 g/dl, nombre absolu de neutrophiles < 1,5 x 109/l, numération plaquettaire <100 x 109/l, créatinine sérique > 1,5 x LSN ou clairance de la créatinine calculée < 30 ml/min
    5. Toute intervention chirurgicale sur l’articulation concernée dans les 12 semaines précédant l'administration de la première dose du traitement à l’étude (à l’exception d’une biopsie synoviale à l'entrée dans l'étude, si elle est pratiquée)
    6. Troubles musculaires cliniquement significatifs actuels ou passés (par exemple myosite), blessure musculaire récente non résolue ou toute pathologie dont on sait qu'elle augmente les taux de CK sérique
    7. Antécédents d'insuffisance cardiaque congestive ou d’infarctus du myocarde < 1 an avant l’administration de la première dose du traitement à l’étude
    8. Fonction cardiaque amoindrie avec un NYHA > classe 2
    9. Trouble cardiaque non contrôlé ou significatif comme l’angor instable
    10. Anomalies importantes à l’ECG à la sélection. QTcF > 450 msec pour les hommes ou > 470 msec pour les femmes à la sélection
    11. Contre-indications à l’IRM et aux produits de contraste à base de gadolinium en intraveineuse
    12. Antécédents de réaction allergique sévère, de réaction anaphylactique ou autre réaction liée à la perfusion d'un agent biologique antérieur
    13. Traitement anticancéreux quelconque ou participation à une autre étude clinique thérapeutique avec des produits expérimentaux ≤ 28 jours avant la prise de la première dose de FPA008
    14. Antécédents connus d'anticorps anti-médicament contre des agents biologiques antérieurs
    15. Antécédents connus de sensibilité au Tween 20 (polysorbate 20)
    16. Consommation régulière de lait non pasteurisé ou risque important connu d’exposition à des infections opportunistes intracellulaires comme listeria ou autres agents pathogènes similaires.
    17. Réception d’un vaccin dans les 28 jours précédant le premier jour du traitement. L’effet du FPA008 sur la réponse immunitaire au vaccin est inconnu. Des vaccins contre la grippe ou autres pourront être administrés pendant l’étude mais l’effet du FPA008 sur la sécurité et l’efficacité de la vaccination est inconnu.
    18. Infection actuelle non résolue ou infection chronique active cliniquement significative (virale [par ex. VHB, VHC] bactérienne, fongique ou autre), qui, de l’avis de l’investigateur, couplée à l'exposition à un inhibiteur du récepteur de CSF1 ferait courir un risque au patient
    19. Positivité connue au virus de l'immunodéficience humaine (VIH)
    20. Tuberculose active
    21. Positivité à une tuberculose latente à la visite de sélection (test QuantiFERON)
    22. Antécédents de tumeur maligne antérieure, sauf :
    – Tumeur maligne cutanée autre que mélanome, traitée curativement
    – Cancer du col utérin in situ
    – Tumeur solide traitée curativement plus de deux ans auparavant, sans signe de récidive
    23. Absence d’accès veineux périphérique ou toute pathologie susceptible d’interférer avec l’administration du médicament ou le prélèvement des échantillons de l’étude
    24. Toute pathologie médicale ou tout trouble psychiatrique non contrôlé(e) qui, de l’avis de l’investigateur, mettrait la sécurité du patient en danger ou perturberait sa participation à l’étude ou l’interprétation des résultats individuels du patient
    25. Incapacité à se soumettre à l’étude et/ou à respecter les procédures de suivi
    E.5 End points
    E.5.1Primary end point(s)
    Phase 1: The incidence of Grade 3 and Grade 4 adverse events (AEs) and clinical laboratory abnormalities defined as dose-limiting toxicities (DLTs)
    Phase 2: The incidence of confirmed objective responses per RECIST 1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    Please refer to protocol
    E.5.2Secondary end point(s)
    PK parameters
    The incidence of AEs, clinical laboratory abnormalities, retinal findings, and ECG abnormalities
    Duration of response per RECIST 1.1
    E.5.2.1Timepoint(s) of evaluation of this end point
    See protocol
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Phase 1/2 study
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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 No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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
    France
    Korea, Republic of
    Netherlands
    Poland
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    Dernière visite du dernier patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    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 No
    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) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 45
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 25
    F.4.2.2In the whole clinical trial 45
    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 Decision2015-07-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-08-25
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-12-30
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