Stránka klinických studií Nct

Summary
EudraCT Number:2014-003346-27
Sponsor's Protocol Code Number:ATYR1940-C-003
National Competent Authority:Italy - Italian Medicines Agency
Clinical Trial Type:EEA CTA
Trial Status:Prematurely Ended
Date on which this record was first entered in the EudraCT database:2021-01-19
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
A. Protocol Information
A.1Member State ConcernedItaly - Italian Medicines Agency
A.2EudraCT number2014-003346-27
A.3Full title of the trial
An Open-Label, Intrapatient Dose-Escalation Study to Evaluate the Safety, Tolerability, Immunogenicity, and Biological Activity of ATYR1940 in Patients With Early Onset and Other Pediatric Onset Facioscapulohumeral Muscular Dystrophy
Uno studio, dose-escalation, intra-paziente, in aperto per valutare la sicurezza, la tollerabilit¿, l¿immunogenicit¿ e l¿attivit¿ biologica di ATYR1940 in pazienti affetti da distrofia muscolare facioscapolomerale ad insorgenza precoce e ad altra insorgenza pediatrica
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
A Study to Evaluate the Safety, Tolerability, Immunogenicity and Biological Activity of ATYR1940 in Patients With Pediatric Onset FHSD
Uno studio per valutare la sicurezza, la tollerabilit¿, l¿immunogenicit¿ e l¿attivit¿ biologica di ATYR1940 in pazienti affetti da distrofia muscolare facioscapolomerale ad insorgenza pediatrica
A.3.2Name or abbreviated title of the trial where available
na
na
A.4.1Sponsor's protocol code numberATYR1940-C-003
A.5.4Other Identifiers
Name:IND NumberNumber:122045
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 SponsorATYR PHARMA, 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 supportATYR PHARMA, INC.
B.4.2CountryUnited States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationVOISIN CONSULTING
B.5.2Functional name of contact pointClinical Trial Operations
B.5.3 Address:
B.5.3.1Street Address3 rue des Longs Pr¿s
B.5.3.2Town/ cityBoulogne-Billancourt
B.5.3.3Post code92100
B.5.3.4CountryFrance
B.5.4Telephone number0033 1 41 31 83 00
B.5.5Fax number0033 1 41 31 83 09
B.5.6E-mailclinicaltrialinformation@voisinconsulting.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 Yes
D.2.5.1Orphan drug designation numberEU/3/15/1448
D.3 Description of the IMP
D.3.1Product nameATYR1940
D.3.2Product code ATYR1940
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.3.9.2Current sponsor codeATYR1940
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 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 Information not present in EudraCT
D.3.11.3.2Gene therapy medical product Information not present in EudraCT
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
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 Yes
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 placeboSolution 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
Early Onset and Other Pediatric Onset Facioscapulohumeral Muscular Dystrophy
distrofia muscolare facioscapolomerale ad insorgenza precoce e ad altra insorgenza pediatrica
E.1.1.1Medical condition in easily understood language
Genetic myopathy
distrofie muscolari genetiche
E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10064087
E.1.2Term Facioscapulohumeral muscular dystrophy
E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
To evaluate the safety, tolerability, and immunogenicity of weekly intravenous (IV) administration of ATYR1940, at doses of 0.3, 1.0, and 3.0 mg/kg, to patients with early onset FSHD
Valutare la sicurezza, la tollerabilit¿ e l¿immunogenicit¿ della somministrazione settimanale di ATYR1940 per via endovena (EV) in dosi da 0.3, 1.0 e 3.0 mg/kg in pazienti con insorgenza precoce della distrofia muscolare facio-scapolo-omerale (FSHD).
E.2.2Secondary objectives of the trial
To explore the biological and pharmacodynamic (PD) activity of ATYR1940 in patients with early onset FSHD, based on changes in
- Inflammatory immune state in peripheral blood
- Muscle strength
- Upper and lower extremity muscle function
- Muscle disease burden, based on skeletal muscle MRI
- Patient-reported quality of life
Esplorare l¿attivit¿ biologica e farmacodinamica (PD) dell¿ATYR1940 in pazienti con insorgenza precoce di FSHD sulla base dei seguenti cambiamenti
- stato immunitario con infiammazione nel sangue periferico
- forza muscolare
- funzionalit¿ muscolare degli arti superiori ed inferiori
- carico della malattia a livello muscolare, valutato sulla base di una risonanza magnetica a livello muscolare e scheletrico
- qualit¿ della vita riferita dal paziente
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. Male or female, between the ages of 16 and 25 years, inclusive, in Stage 1 and 12 and 15 years, inclusive, in Stage 2.
2. Established, genetically confirmed diagnosis of FSHD (Type 1 or 2).
3. Onset of FSHD signs or symptoms (e.g., facial weakness, scapular winging, weakness in upper or lower extremities) prior to 10 years of age, as documented in the patient's medical record or based on patient or family report.
4. Provide written informed consent or assent (as appropriate, based on age of majority).
5. In the Investigator's opinion, patient is willing and able to complete all study procedures and comply with the weekly study visit schedule
1. Paziente maschio o femmina, di età compresa tra 16 e 25 anni compresi, nella Fase 1 e 12 e 15 anni compresi, nella Fase 2
2. Paziente con diagnosi dimostrata, geneticamente confermata, di FSHD (Tipo 1 o 2).
3. Insorgenza di segni o sintomi di FSHD (ad es., debolezza facciale, scapole alate, debolezza degli arti superiori ed inferiori) prima dei 10 anni di età, come indicato nella cartella clinica del paziente o come riferito dal paziente o dalla sua famiglia.
4. Paziente che ha fornito il consenso o l’assenso informato (a seconda dei casi, in base alla maggiore età).
5. Paziente che, secondo il parere del Ricercatore, è desideroso e in grado di seguire tutte le procedure dello studio e di rispettare il programma settimanale delle visite previste dallo studio.
E.4Principal exclusion criteria
1. Currently receiving treatment with an immunomodulatory agent or history of such treatment, including targeted biological therapies (e.g., etanercept, omalizumab) within the 3 months before baseline; corticosteroids within 3 months before baseline; or high-dose nonsteroidal
anti-inflammatory agents (NSAIDs; either chronic or intermittent) within 2 weeks before baseline.
2. Currently receiving curcumin or albuterol or requires such treatment during study participation; use of a product that putatively enhances muscle growth (e.g., insulin-like growth factor, growth hormone) or activity (e.g., Coenzyme Q, Coenzyme A, creatinine, L-carnitine) on a chronic basis within 4 weeks before baseline; statin treatment initiatio or significant adjustment to statin regimen within 3 months before baseline (stable, chronic statin use is permissible).
3. Use of an investigational product or device (other than a mobility assistance device) within 30 days before baseline.
4. Evidence of an alternative diagnosis other than FSHD or a co-existing myopathy or dystrophy, based on prior muscle biopsy or other available investigations.
5. History of severe restrictive or obstructive lung disease (including interstitial lung disease, pulmonary fibrosis, or asthma), or evidence for interstitial lung disease on screening chest radiograph.
6. History of anti-synthetase syndrome, prior Jo-1 Ab-positivity, or Jo 1 Ab level = 0.6 U/mL on screening.
7. Acute or clinically relevant Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection or re-activation.
8. Chronic infection, such as hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) or a history of tuberculosis.
9. Vaccination within 8 weeks before baseline or vaccination is planned during study participation.
10. Evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, dermatological, or gastrointestinal disease, cognitive impairment, or a condition that requires immediate surgical intervention or other treatment, or may not allow safe participation in the study.
11. Muscle biopsy within 30 days before baseline.
1. Attualmente il paziente sta ricevendo un trattamento con un agente immunomodulante o ha seguito in precedenza tale trattamento, comprese terapie biologiche mirate (ad es. etanercept, omalizumab) nei 3 mesi precedenti la visita baseline; corticosteroidi nei 3 mesi precedenti la visita baseline; o agenti antinfiammatori non-steroidei (NSAID) a dosaggio elevato (cronico o intermittente) nelle 2 settimane prima della visita baseline.
2. Attualmente il paziente sta ricevendo curcumina o albuterolo o esige un trattamento di questo tipo durante la partecipazione allo studio; sta utilizzando un prodotto che si ritiene possa potenziare la crescita muscolare (ad es., fattore di crescita insulino-simile, ormone della crescita) o l’attività muscolare (ad es., Coenzima Q, Coenzima A, creatina, L-carnitina) su base cronica nelle 4 settimane precedenti la visita baseline; il paziente ha iniziato un trattamento con una statina oppure il suo regime con la statina ha subito una correzione significativa nei 3 mesi precedenti la visita baseline (l’uso cronico e stabile di statina è ammesso).
3. Il paziente ha usato prodotti o dispositivi di ricerca (diversi da un dispositivo di deambulazione) nei 30 giorni precedenti la visita baseline;
4. Evidenze di una diagnosi alternativa diversa dalla FSHD o di miopatia o distrofia coesistenti, basate su una biopsia muscolare precedente o su altre indagini disponibili.
5. Precedenti di una malattia polmonare restrittiva o ostruttiva (compresa malattia interstiziale polmonare, fibrosi polmonare o asma), o evidenza di una malattia interstiziale polmonare in base a una radiografia al torace eseguita durante lo screening.
6. Il paziente ha un precedente di sindrome anti-sintetasi, una precedente positività all’anticorpo Jo-1 (Ab) o ha livelli di Jo-1 Ab = 0.6 U/mL allo screening.
7. Il paziente ha un’infezione o una ri-attivazione acuta o clinicamente rilevante del virus di Epstein-Barr o del citomegalovirus (CMV).
8. Il paziente ha un’infezione cronica come il virus dell’epatite B, dell’epatite C o il virus da immunodeficienza umana (HIV) o un precedente di tubercolosi.
9. Il paziente ha ricevuto una vaccinazione nelle 8 settimane precedenti la visita baseline o è programmata una vaccinazione durante la sua partecipazione allo studio.
10. Il paziente ha evidenza di malattia cardiovascolare, polmonare, epatica, renale, ematologica, metabolica, dermatologica o gastrointestinale clinicamente significativa, deterioramento cognitivo o è in uno stato che richiede un intervento chirurgico immediato o un altro trattamento, o che potrebbe non consentire una partecipazione sicura allo studio.
11. Il paziente è stato sottoposto a una biopsia muscolare nei 30 giorni precedenti la visita baseline.
E.5 End points
E.5.1Primary end point(s)
Safety and tolerability
• Incidence of treatment-emergent AEs and SAEs overall and by intensity.
• Changes from baseline in:
- Safety laboratory test results
- ECG findings
- Vital signs measurements
- Pulmonary evaluations
- Visual acuity and retinal morphology
- Hearing

Immunogenicity
• Incidence and level of ADA titers and Jo-1 Ab.
• Exploratory characterization of immune response to ATYR1940.
Sicurezza e la tollerabilità
• Incidenza degli AE emergenti dal trattamento e dei SAE complessivi e per intensità.
• Cambiamenti rispetto ai valori baseline di
- Risultati dei test di laboratorio sulla sicurezza
- Esiti degli ECG
- Misurazioni dei segni vitali
- Valutazioni polmonari
- Acutezza visiva e morfologia retinica
- Udito

Immunogenicità:
• Incidenza e livello dei titoli ADA e dell’anticorpo Jo-1 Ab.
• Caratterizzazione esploratoria della risposta immune ad ATYR1940.
E.5.1.1Timepoint(s) of evaluation of this end point
AEs & vital signs: throughout the study
Safety laboratory tests: at Screening and at weeks 1 to 4, 6, 8, 10, 12, 14, 17 and 25
ECG: at Screening, at week 2, 4, 8/9, 13 and 14
Pulmonary function tests: at Screnning, at weeks 3, 5, 8/9, 13 and 17
Pulse oximetry: weeks 1 to 13
Visual acuity, retinal morphology & Hearing: at Screening and at week 13

ADA titers: at Screening and at weeks 4, 6, 8, 10, 13, 14, 17 and 25
Jo-1 Ab: at Screening and at week 3 to 25
Plasma complement levels: weeks 1, 4, 8 and 14
Serum complement and tryptase levels: weeks 1 and 14
Eventi avversi & segni vitali: nel corso dello studio
Valutazioni di laboratorio sulla sicurezza: Screening e settimane 1 a 4, 6, 8, 10, 12, 14, 17 e 25
ECG: Screening, settimane 2, 4, 8/9, 13 e 14
Test della funzionalità polmonare: Screnning, settimane 3, 5, 8/9, 13 e 17
Pulsossimetria: settimana 1 a 13
Acutezza visive, morfologia retinica & audiometria: Screening e settimana 13

Titoli ADA: Screening e settimane 4, 6, 8, 10, 14, 17 e 25
Anticorpo Jo-1 Ab: Screening e settimana 3 a 25
Livelli plasmatici del complemento: settimane 1, 4, 8 e 14
Livelli sierici di complemento e triptasi: settimane 1 e 14
E.5.2Secondary end point(s)
PD activity
¿ Changes in FSHD-related inflammatory immune state in peripheral blood.
¿ Changes from baseline in the following clinical parameters:
- Muscle strength
- Upper and lower extremity muscle function
- Lower extremity muscle disease burden, based on muscle MRI
- Quality of life
Attivit¿ PD:
¿ Cambiamenti nello stato immunitario infiammatorio correlato a FSHD nel sangue periferico.
¿ Cambiamenti nei seguenti parametri clinici rispetto ai valori baseline:
- Forza muscolare
- Funzionalit¿ muscolare degli arti superiori ed inferiori
- Carico della malattia muscolare negli arti inferiori, valutato sulla base di una risonanza magnetica a livello muscolare
- Qualit¿ della vita
E.5.2.1Timepoint(s) of evaluation of this end point
Immunophenotyping and culture for immune protein release: at Screening and at weeks 1, 9 and 14
MMT & Upper and lower extremity muscle function: at Screening and at weeks 7, 10 and 14
MRI: at Screening and at week 14
INQoL: at Screening and at weeks 7, 14 and 25
Immunofenotipizzazione e coltura per rilascio di proteine immunitarie:
Screening e settimane 1, 9 e 14
MMT & Funzionalit¿ muscolare degli arti superiori ed inferiori: Screening e settimane 7, 10 e 14
MRI: Screening e settimana 14
INQoL: Screening e settimane 7, 14 e 25
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 Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Tolerability, immunogenicity
tollerabilit¿, immunogenicit¿
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 1b/2: Safety, Tolerability, Immunogenicity and Pharmacodynamics
Fase 1b/2 : sicurezza, tollerabilit¿ e farmacodinamica
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 No
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.8.3 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 EEA2
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 Information not present in EudraCT
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
Italy
United States
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
LVLS, including the 12-week follow-up visit
LVLS, tra cui la visita di follow-up di 12 settimana
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 months6
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years1
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 Yes
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: 8
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 8
F.1.3Elderly (>=65 years) No
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 state4
F.4.2 For a multinational trial
F.4.2.1In the EEA 8
F.4.2.2In the whole clinical trial 16
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)
Subjects will return to their standard of care treatment as determined by their physician after completion of the trial.
I soggetti torneranno al loro trattamento di cura abituale, come stabilito dal medico, dopo il completamento della sperimentazione.
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 Decision2015-11-06
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

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