Stránka klinických studií Nct

Summary
EudraCT Number:2022-001771-14
Sponsor's Protocol Code Number:SRK-015-004
National Competent Authority:Spain - AEMPS
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-12-20
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
A. Protocol Information
A.1Member State ConcernedSpain - AEMPS
A.2EudraCT number2022-001771-14
A.3Full title of the trial
An Open-Label, Multicenter, Extension Trial to Evaluate the Long-Term Safety and Efficacy of Apitegromab in Patients with Type 2 and Type 3 Spinal Muscular Atrophy Who Completed Previous Investigational Trials of Apitegromab
Estudio de extensión abierto y multicéntrico para evaluar la seguridad y la eficacia a largo plazo de apitegromab en pacientes con atrofia muscular espinal de tipo II y tipo III que completaron estudios de investigación previos del apitegromab
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Long-Term Safety and Efficacy of Apitegromab in Patients with Type 2 and Type 3 Spinal Muscular Atrophy Who Completed Previous Investigational Trials of Apitegromab
La seguridad y la eficacia a largo plazo de apitegromab en pacientes con atrofia muscular espinal de tipo II y tipo III que completaron estudios de investigación previos del apitegromab
A.3.2Name or abbreviated title of the trial where available
ONYX
A.4.1Sponsor's protocol code numberSRK-015-004
A.5.4Other Identifiers
Name:INDNumber:136 872
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 SponsorScholar Rock, 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 supportScholar Rock, Inc.
B.4.2CountryUnited States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationScholar Rock, Inc.
B.5.2Functional name of contact pointClinical Information Desk
B.5.3 Address:
B.5.3.1Street Address301 Binney Street, 3rd Floor
B.5.3.2Town/ cityCambridge, MA
B.5.3.3Post code02142
B.5.3.4CountryUnited States
B.5.4Telephone number+1857259 3860
B.5.6E-mailclinops@scholarrock.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/3/18/2115
D.3 Description of the IMP
D.3.1Product nameApitegromab
D.3.2Product code SRK-015
D.3.4Pharmaceutical form 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 INNApitegromab
D.3.9.1CAS number 2278276-46-1
D.3.9.2Current sponsor codeSRK-015
D.3.9.4EV Substance CodeSUB193232
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number50
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
Spinal Muscular Atrophy (SMA)
Atrofia muscular espinal (AME)
E.1.1.1Medical condition in easily understood language
Spinal Muscular Atrophy (SMA)
Atrofia muscular espinal (AME)
E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.1
E.1.2Level LLT
E.1.2Classification code 10041583
E.1.2Term Spinal muscular atrophy, unspecified
E.1.2System Organ Class 100000004850
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
Evaluate the long-term safety and tolerability of apitegromab in patients with Type 2 and Type 3 SMA
Evaluar la seguridad y tolerabilidad a largo plazo de apitegromab en pacientes con AME de tipo II y tipo III
E.2.2Secondary objectives of the trial
Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points

Further evaluate the immunogenicity of apitegromab
Evaluar la eficacia a largo plazo de apitegromab mediante la evaluación de los cambios en los criterios de valoración de la función motora en momentos especificados previamente

Evaluar mejor la inmunogenicidad de apitegromab
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. Informed consent document signed by the patient if the patient is legally an adult. If the patient is legally a minor, informed consent document signed by the patient’s parent or legal guardian and patient’s oral or written assent obtained, if applicable and in accordance with the regulatory and legal requirements of the participating location.
2. Patients who have completed the Phase 2 TOPAZ (Study SRK-015-002) trial or the Phase 3 SAPPHIRE (Study SRK-015-003) trial.
3. Estimated life expectancy >2 years from Baseline (Day 1).
4. Able to receive study drug infusions and provide blood samples through the use of a peripheral IV or a long-term IV access device that the patient has placed for reasons independent from the trial (i.e., for background medical care and not for the purpose of receiving apitegromab in the trial), throughout the trial.
5. Able to adhere to the requirements of the protocol.
6. Females of childbearing potential must have a negative pregnancy test at Baseline and agree to use at least 1 acceptable method of contraception throughout the trial and for 20 weeks after the last dose of apitegromab. Female patients who are expected to have reached reproductive maturity by the end of the trial must agree to adhere to trial-specific contraception requirements.
1. Documento de consentimiento informado firmado por el paciente si este es legalmente mayor de edad. Si el paciente es legalmente menor de edad, el documento de consentimiento informado firmado por el progenitor o tutor legal del paciente se obtiene un asentimiento verbal o escrito del paciente, si corresponde y de acuerdo con los requisitos normativos y legales de la ubicación participante.
2. Pacientes que hayan completado el ensayo de fase II TOPAZ (estudio SRK-015-002) o el ensayo de fase III SAPPHIRE (Estudio SRK-015-003).
3. Esperanza de vida estimada > 2 años desde el inicio (día 1).
4. Poder recibir infusiones del fármaco del estudio y proporcionar muestras de sangre mediante el uso de una vía intravenosa periférica o un dispositivo de acceso intravenoso de larga duración que el paciente se haya colocado por razones independientes del ensayo (es decir, para la atención médica de base y no con el fin de recibir apitegromab en el ensayo), durante todo el ensayo.
5. Capaz de cumplir los requisitos del protocolo.
6. Las mujeres en edad fértil deben tener una prueba de embarazo negativa en el inicio y estar de acuerdo en usar al menos un método anticonceptivo aceptable durante todo el ensayo y durante 20 semanas después de la última dosis de apitegromab. Las pacientes que se espera que hayan alcanzado la madurez reproductiva al final del ensayo deben aceptar cumplir los requisitos de anticoncepción específicos del ensayo.
E.4Principal exclusion criteria
1. Patient permanently discontinued study treatment during the feeder trial (i.e., TOPAZ or SAPPHIRE).
2. Nutritional status that was not stable over the past 6 months and is not anticipated to be stable throughout the trial or medical necessity for a gastric/nasogastric feeding tube, where the majority of feeds are given by this route, as assessed by the investigator.
3. Patient is currently enrolled in any investigational drug trial other than TOPAZ or SAPPHIRE.
4. Prior history of severe hypersensitivity reaction or intolerance to SMN-targeted therapies.
5. Prior history of severe hypersensitivity reaction or intolerance to apitegromab.
6. Use of chronic daytime noninvasive ventilatory support for >16 hours daily in the 2 weeks before dosing, or anticipated to regularly receive such daytime ventilator support chronically throughout the trial.
7. Any acute or comorbid condition interfering with the well-being of the patient at the patient’s last visit in TOPAZ or SAPPHIRE, including active systemic infection, the need for acute treatment, or inpatient observation due to any reason.
8. Pregnant or breastfeeding.
9. Any other condition or clinically significant laboratory result or ECG value that, in the opinion of the Investigator, may compromise safety or compliance, would preclude the patient from successful completion of the trial, or interfere with the interpretation of the results.
1. El paciente suspendió permanentemente el tratamiento del estudio durante el ensayo preliminar (es decir, TOPAZ o SAPPHIRE)
2. Estado nutricional que no ha sido estable en los últimos 6 meses y que no se prevé que sea estable a lo largo del ensayo o necesidad médica de una sonda de alimentación gástrica/nasogástrica, cuando la mayoría de las tomas se administran por esta vía, según lo evaluado por el investigador
3. El paciente está actualmente inscrito en cualquier ensayo con el fármaco en investigación que no sea TOPAZ o SAPPHIRE.
4. Antecedentes de reacción de hipersensibilidad grave o intolerancia a las terapias dirigidas a NMS.
5. Antecedentes de reacción de hipersensibilidad grave o intolerancia a apitegromab.
6. Uso de soporte ventilatorio no invasivo diurno crónico durante > 16 horas diarias en las 2 semanas anteriores a la dosis, o que se prevea que va a recibir regularmente dicho soporte ventilatorio diurno de forma crónica durante todo el ensayo
7. Cualquier afección aguda o comórbida que interfiera en el bienestar del paciente en la última visita del paciente en TOPAZ o SAPPHIRE, incluida la infección sistémica activa, la necesidad de tratamiento agudo o la observación hospitalaria por cualquier motivo.
8. Embarazada o en período de lactancia.
9. Cualquier otra afección o resultado de laboratorio o valor del ECG clínicamente significativo que, según el dictamen del investigador, pueda poner en peligro la seguridad o el cumplimiento terapéutico, que impida al paciente completar con éxito el ensayo o que interfiera en la interpretación de los resultados.
E.5 End points
E.5.1Primary end point(s)
Incidence of TEAEs and SAEs by severity
Incidencia de AADT y AAG por gravedad
E.5.1.1Timepoint(s) of evaluation of this end point
Evaluted at timepoints as described in the protocol
Evaluados en los puntos de tiempo como se describe en el protocolo
E.5.2Secondary end point(s)
- HFMSE total score at prespecified time points (excludes TOPAZ Cohort 1 patients)
- RULM total score at prespecified time points (excludes TOPAZ Cohort 1 patients)
- Number of WHO motor development milestones attained at prespecified time points (excludes TOPAZ Cohort 1 patients)
- RHS total score and results for 6-Minute Walk Test, 30-Second Sit-to-Stand, 10-Meter Walk/Run (from the RHS), and timed rise from floor (from the RHS) at prespecified time points (TOPAZ Cohort 1 patients only)
- Puntuación total de la escala motriz funcional de Hammersmith ampliada (Hammersmith Functional Motor Scale Expanded, HFMSE) en momentos de evaluación especificados previamente (excluidos los pacientes de la cohorte 1 de TOPAZ)
- Puntuación total del módulo revisado para la evaluación de las extremidades superiores (Revised Upper Limb Module, RULM) en puntos temporales especificados previamente (excluidos los pacientes de la cohorte 1 de TOPAZ)
- Número de hitos de desarrollo motriz de la Organización Mundial de la Salud (OMS) alcanzados en puntos temporales especificados previamente (excluidos los pacientes de la cohorte 1 de TOPAZ)
- Puntuación total de la escala revisada de Hammersmith (Revised Hammersmith Scale, RHS) y resultados de la prueba de marcha de 6 minutos, la prueba de sentarse y levantarse en 30 segundos, la prueba de marcha/carrera de 10 metros (de la RHS) y la prueba de elevación cronometrada desde el suelo (de la RHS) en puntos temporales especificados previamente (solo pacientes de la Cohorte 1 de TOPAZ)
E.5.2.1Timepoint(s) of evaluation of this end point
Evaluted at timepoints as described in the protocol
Evaluados en los puntos de tiempo como se describe en el protocolo
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 Yes
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
Immunogenicity, tolerability
Inmunogenicidad, tolerabilidad
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 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 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 concerned2
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA28
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
United States
France
Poland
Netherlands
Spain
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
LVLS
La última visita del último paciente
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years2
E.8.9.1In the Member State concerned months5
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years2
E.8.9.2In all countries concerned by the trial months5
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: 235
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) Yes
F.1.1.5.1Number of subjects for this age range: 182
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 53
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 27
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 Yes
F.3.3.6.1Details of subjects incapable of giving consent
Minors
Menores
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state8
F.4.2 For a multinational trial
F.4.2.1In the EEA 263
F.4.2.2In the whole clinical trial 260
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)
NA
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 Decision2023-05-08
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2023-04-18
P. End of Trial
P.End of Trial StatusOngoing

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit