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SNCTP000004576 | NCT04680637 | BASEC2021-00736

Beurteilung der Wirksamkeit und Sicherheit von Efavaleukin alfa bei Personen mit aktivem systemischem Lupus erythematodes, die nicht ausreichend auf die Standardtherapie angesprochen haben

Base di dati: BASEC (Importata da 27.01.2022), WHO (Importata da 18.01.2022)
Cambiato: 18.01.2022
Categoria di malattie: Altro

Descrizione riassuntiva della sperimentazione (Fonte di dati: BASEC)

Systemischer Lupus erythematodes ist eine Multisystem-Autoimmunerkrankung unbekannter Ursache mit vielfältigen klinischen Manifestationen. Systemischer Lupus erythematodes kann die Haut, den Bewegungsapparat, das Nervensystem, die Lunge, Herz und Kreislauf, die Nieren und das Blut betreffen.
Um eine aktive Lupus-Erkrankung unter Kontrolle zu bringen, werden derzeit Corticosteroide, Immunsuppressiva, Immunmodulatoren und zytotoxische Wirkstoffe eingesetzt. Es besteht jedoch ein erheblicher Bedarf an Behandlungsmöglichkeiten mit höherer Wirksamkeit und geringerer Kurz- und Langzeittoxizität.
An dieser Studie werden weltweit 320 Patienten teilnehmen. Die Dauer der Studie für den einzelnen Patienten beträgt 56 Wochen (einschließlich der Sicherheitsbeobachtungsphase) zuzüglich der Voruntersuchungsphase (Screening). Die Behandlung wird alle zwei Wochen als subkutane Injektion verabreicht; die letzte Verabreichung findet in Woche 50 statt. Alle Patienten werden nach der letztmaligen Gabe des Prüfpräparats für 6 Wochen einer Sicherheitsbeobachtung unterzogen.
Das Ziel in Bezug auf die Wirksamkeit besteht darin, die Überlegenheit der Behandlung im Vergleich zur Placebo-Kontrollgruppe (in der keine arzneilich wirksame Substanz verabreicht wird) nachzuweisen.

Malattie studiate (Fonte di dati: BASEC)

Aktiver systemischer Lupus erythematodes mit ungenügendem Ansprechen auf die Standardtherapie

Health conditions (Fonte di dati: WHO)

Active Systemic Lupus Erythematosus

Malattia rara (Fonte di dati: BASEC)

No

Interventi esaminati (p. es. medicamento, terapia, campagna) (Fonte di dati: BASEC)

Efavaleukin alfa ist eine Substanz, die mit der Zielsetzung entwickelt wurde, ihre Selektivität im Vergleich mit einem anderen, bereits untersuchten Wirkstoff zu erhöhen. Die neue Substanz scheint ausserdem stabiler zu sein als die zuvor verwendete, was eine geringere Verabreichungshäufigkeit ermöglicht, ohne Abstriche bei der erwarteten Wirkung machen zu müssen.
Diese Dosisfindungsstudie der Phase 2b, in der die Behandlung nach dem Zufallsprinzip (wie beim Werfen einer Münze) festgelegt wird und weder Sie noch Ihr Arzt wissen, welche Behandlung Sie erhalten, dient der Beurteilung der Sicherheit und Wirksamkeit dreier verschiedener Dosierungen von Efavaleukin alfa im Vergleich mit Placebo bei Patienten mit aktivem systemischem Lupus erythematodes, die nicht ausreichend auf die Standardtherapie angesprochen haben.

Interventions (Fonte di dati: WHO)

Drug: Efavaleukin Alfa;Drug: Placebo;Other: Standard of Care

Criteri per la partecipazione alla sperimentazione (Fonte di dati: BASEC)

- Personen im Alter von 18 bis 75 Jahren, die im Rahmen der Voruntersuchung (Screening) vor der Durchführung jeglicher studienspezifischer Maßnahmen/Verfahren eine Einwilligungserklärung abgegeben haben.
- Die Studienteilnehmer müssen eines der folgenden Arzneimittel zur SLE-Behandlung (oder ein regionsspezifisches gleichwertiges Ersatzpräparat) einnehmen: Mycophenolat-Mofetil, Azathioprin, Methotrexat, Hydroxychloroquin, Chloroquin, Dapson, Quinacrin, orale Calcineurin-Inhibitoren oder orale Corticosteroide (OCS). Eine Teilnahme an der Studie unter alleiniger Behandlung mit einem OCS (Prednison  10 mg/Tag oder gleichwertiges Präparat) ist nur dann möglich, wenn bereits ein dokumentierter Therapieversuch mit einem gegen SLE wirksamen Anti-Malaria-Mittel oder Immunsuppressivum stattgefunden hat. Für sämtliche Anti-Malaria-Mittel und Immunsuppressiva gilt, dass die Studienteilnehmer über einen Zeitraum von ≥ 8 Wochen vor der Voruntersuchung eine unveränderte Dosierung erhalten haben müssen, während die Dosierung von OCS über einen Zeitraum von  2 Wochen vor der Voruntersuchung unverändert geblieben sein muss.

Criteri di esclusione (Fonte di dati: BASEC)

- Aktiver Lupus des Zentralnervensystems (ZNS) innerhalb von 1 Jahr vor der Voruntersuchung
- Aktuelles Leiden an einer anderen entzündlichen Gelenk- oder Hauterkrankung als SLE oder Diagnose einer solchen Erkrankung innerhalb eines Zeitraums von 1 Jahr vor der Voruntersuchung
- Aktive Infektion (einschließlich chronischer oder lokal begrenzter Infektionen), für die eine Behandlung mit Antiinfektiva angezeigt war, innerhalb von 4 Wochen vor dem Voruntersuchungstermin oder Vorliegen einer schwerwiegenden Infektion (definiert als Infektion, die einen Spitalaufenthalt oder eine intravenöse Behandlung mit Antiinfektiva erfordert hat) innerhalb von 8 Wochen vor dem Voruntersuchungstermin.

Inclusion/Exclusion Criteria (Fonte di dati: WHO)


Inclusion Criteria:

- Participant has provided informed consent prior to initiation of any study specific
activities/procedures.

- Participant is aged between 18 and 75.

- Fulfills classification criteria for systemic lupus erythematosus (SLE) according to
the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology
(ACR) classification criteria for SLE with antinuclear antibody = 1:80 by
immunofluorescence on Hep-2 cells being present at screening.

- Hybrid SLEDAI score = 6 points with a Clinical hSLEDAI score = 4 points. The
Clinical hSLEDAI is the hSLEDAI assessment score without the inclusion of points
attributable to laboratory results, including urine or immunologic parameters.

- British-Isles Lupus Assessment Group (BILAG) index score (BILAG 2004) of = 1 A item or
= 2 B items.

- Must be taking = 1 of the following SLE treatments (or regional equivalent):
hydroxychloroquine, chloroquine, quinacrine, mycophenolate mofetil, azathioprine,
methotrexate, dapsone, or oral calcineurin inhibitors, or OCS. A participant may enter
the study on OCS alone (prednisone = 10 mg/day or equivalent) only if the participant
has previously documented trial of anti-malarial or immunosuppressant treatment for
SLE. Participants must be on a stable dose for = 8 weeks prior to screening for all
antimalarials and immunosuppressants, with the exception of OCS doses which must be
stable for = 2 weeks prior to screening.

- For participants taking OCS, dose must be = 20 mg/day of prednisone or OCS equivalent,
and the dose must be stable at baseline visit and for = 2 weeks prior to screening
visit.

- Stability of SLE treatments: OCS and other immunosuppressants/immunomodulator agents
and doses must be stable since screening visit.

- Disease activity: active disease as indicated by clinical hSLEDAI score = 4 must be
observed (clinical hSLEDAI score is the hSLEDAI assessment score without the inclusion
of points attributable to laboratory results including urine and immunologic
parameters).

Exclusion Criteria:

- Lupus nephritis if any of the following are present: urine protein creatinine ratio =
2000 mg/g (or equivalent) at screening, OR having required induction therapy within 1
year prior to screening, OR histological evidence (if available) of diffuse
proliferative glomerulonephritis within 12 weeks prior to screening.

- Active CNS lupus within 1 year prior to screening including, but not limited to,
aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating
syndrome, optic neuritis, psychosis, seizures, or transverse myelitis.

- Currently present or within 1 year prior to screening a diagnosis of any chronic
inflammatory disease other than SLE (eg, rheumatoid arthritis) which would interfere
with SLE disease assessment.

- History of any disease other than SLE that has required treatment with oral or
parenteral corticosteroids for > 2 weeks within 4 months prior to screening.

- Active infection (including chronic or localized infections) for which anti-infectives
were indicated within 4 weeks prior to screening visit OR presence of serious
infection, defined as requiring hospitalization or intravenous anti-infectives within
8 weeks prior to screening visit.

- Active tuberculosis or latent tuberculosis with no documented past history of adequate
treatment per local standard of care.

- Positive test for tuberculosis during creening defined as: either a positive or
indeterminate QuantiFERON®-TB or T-spot test OR positive purified protein derivative
(PPD) (=5 mm of induration at 48 to 72 hours after test is placed).

- Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core
antibody (HBcAb). A history of hepatitis B vaccination without history of hepatitis B
infection (ie, positive hepatitis B surface antibody (HBsAb), negative HBsAg and
negative HBcAb) is allowed.

- Positive for hepatitis C antibody.

- Known history of HIV or positive HIV test at screening.

- Presence of 1 or more significant concurrent medical conditions, including but not
limited to the following:

- poorly controlled diabetes (hemoglobin A1C > 7) or hypertension

- symptomatic heart failure (New York Heart Association class III or IV)

- myocardial infarction or unstable angina pectoris within the past 12 months prior
to screening

- severe chronic pulmonary disease requiring oxygen therapy

- multiple sclerosis or any other demyelinating disease

- Any history of malignancy with the following exceptions:

- resolved non-melanoma skin cancers > 5 years prior to screening

- resolved cervical carcinoma > 5 years prior to screening

- resolved breast ductal carcinoma in situ > 5 years of screening

- Currently receiving or had treatment with: cyclophosphamide, chlorambucil, nitrogen
mustard, or any other alkylating agent within 6 months prior to screening or sirolimus
within 4 weeks prior screening.

- Currently receiving or had treatment with a Janus kinase (JAK) inhibitor within 3
months or less than 5 drug half-lives (whichever is longer) prior to screening.

- Currently receiving or had treatment with an immune checkpoint inhibitor (eg,
programmed death 1 [PD-1] inhibitor, programmed death ligand 1 [PD-L1] inhibitor,
cytotoxic T-lymphocyte associated protein 4 [CTLA-4] inhibitor).

Note: Abatacept is not considered a CTLA-4 inhibitor and is referred to below.

- Currently receiving or had treatment within 12 months prior to screening with T-cell
depleting agents (eg, antithymocyte globulin, Campath).

- Currently receiving of had treatment with an interleukin 2 (IL-2) based therapy (eg,
Proleukin).

- Current or previous treatment with a biologic agent as follows: rituximab within 6
months prior to screening; abatacept and belimumab within the past 3 months prior to
screening; other biologics within < 5 drug half lives prior to screening.

- Participants who have received intraarticular, intralesional, or intramuscular
corticosteroids within 2 weeks prior to screening or intravenous corticosteroids
within 6 weeks prior to screening.

- Participants who have received live vaccines within 5 weeks prior to screening, or
plan to receive live vaccines during the treatment period and up to 6 weeks after the
end of treatment period in the study.

- Currently receiving

Altri dati sulla sperimentazione nel registro primario dell’OMS

https://clinicaltrials.gov/show/NCT04680637

Altri dati sulla sperimentazione dalla banca dati dell’OMS (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04680637

Altre informazioni sulla sperimentazione

Data di registrazione della sperimentazione

18.12.2020

Inserimento del primo partecipante

06.05.2021

Stato di reclutamento

Recruiting

Titolo scientifico (Fonte di dati: WHO)

A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus With Inadequate Response to Standard of Care Therapy

Tipo di sperimentazione (Fonte di dati: WHO)

Interventional

Disegno della sperimentazione (Fonte di dati: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).

Fase (Fonte di dati: WHO)

Phase 2

Punti finali primari (Fonte di dati: WHO)

Percent of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 52

Punti finali secondari (Fonte di dati: WHO)

Percent of Participants Achieving a British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 24 and Week 52;Percent of Participants Achieving a Lupus Low Disease Activity State (LLDAS) Response at Week 52;Percent of Participants with a Reduction of Oral Corticosteroid (OCS) to Less Than or Equal to 7.5 mg/day by Week 44 and Sustained Through Week 52 in Participants with a Baseline OCS Dose = 10 mg/day;Percent of Participants Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24;Percent of Participants Achieving a Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) Response at Week 24 and Week 52;Tender and Swollen Joint Count = 50% Improvement from Baseline at Weeks 8, 12, 24, 36, and 52 in Participants with = 6 Tender and Swollen Joints Involving the Hands and Wrists at Baseline;Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Activity Score = 50% Improvement from Baseline at Week 8, 12, 24, 36, and 52 in Participants with a CLASI Activity Score = 8 at Baseline;Percent of Participants who Experience a Flare;Change from Baseline in Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a Instrument (PROMIS Fatigue SF 7A) Fatigue Score;Change from Baseline in Medical Outcomes Short Form-36 Questionnaire Score;Change from Baseline in Lupus Quality of Life (QoL) Questionnaire Score;Number of Participants who Experience a Treatment-Emergent Adverse Event (AE) and Serious Adverse Event (SAE);Number of Participants who Experience a Clinically Significant Change in Laboratory Values and Vital Sign Measurements;Trough Serum and Sparse Postdose Serum Concentration of Efavaleukin Alfa

Contatto per informazioni (Fonte di dati: WHO)

Please refer to primary and secondary sponsors

Risultati della sperimentazione (Fonte di dati: WHO)

Sintesi dei risultati

ancora nessuna informazione disponibile

Collegamento ai risultati nel registro primario

ancora nessuna informazione disponibile

Informazioni sulla disponibilità dei dati dei singoli partecipanti

ancora nessuna informazione disponibile

Siti di esecuzione della sperimentazione

Siti di esecuzione in Svizzera (Fonte di dati: BASEC)

Basilea, San Gallo

Paesi di esecuzione (Fonte di dati: WHO)

Austria, Bulgaria, Greece, Hong Kong, Italy, Japan, Korea, Mexico, Poland, Republic of, Russian Federation, Spain, Switzerland, Taiwan, Turkey, United States

Contatto per maggiori informazioni sulla sperimentazione

Dati della persona di contatto in Svizzera (Fonte di dati: BASEC)

Dr. Thomas Schwaller
+41 41 3692520
tschwall@amgen.com

Contatto per informazioni generali (Fonte di dati: WHO)

MD;Amgen Call Center
Amgen
866-572-6436
medinfo@amgen.com

Contatto per informazioni scientifiche (Fonte di dati: WHO)

MD;Amgen Call Center
Amgen
866-572-6436
medinfo@amgen.com

Responsabile della sperimentazione

Sponsor principale (Fonte di dati: WHO)

Amgen

Autorizzazione da parte della commissione d’etica (Fonte di dati: BASEC)

Nome della commissione d’etica che rilascia l’autorizzazione (nel caso di studi multicentrici solo la commissione direttiva)

Ethikkommission Ostschweiz (EKOS)

Data di autorizzazione da parte della commissione d’etica

12.08.2021

Altri numeri di identificazione delle sperimentazioni

Numero di identificazione della sperimentazione della commissione d’etica (BASEC-ID) (Fonte di dati: BASEC)

2021-00736

Secondary ID (Fonte di dati: WHO)

20200234