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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

Data source: BASEC (Imported from 29.11.2021), WHO (Imported from 18.04.2021)
Changed: 25.11.2021
Disease category: Other

Brief description of trial (Data source: 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.

Health conditions investigated (Data source: BASEC)

Aktiver systemischer Lupus erythematodes mit ungenügendem Ansprechen auf die Standardtherapie

Health conditions (Data source: WHO)

Active Systemic Lupus Erythematosus

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: 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 (Data source: WHO)

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

Criteria for participation in trial (Data source: 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.

Exclusion criteria (Data source: 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 (Data source: 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.

Exclusion Criteria:

- Lupus nephritis with urine protein creatinine ratio = 3000 mg/g (or equivalent) at
screening or having required induction therapy within 1 year 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 inflammatory
joint or skin disease other than SLE (confirmed by the investigator) which would
interfere with SLE disease assessment based on investigator judgement.

- 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.

- 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 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, PD-1
inhibitor, PD-L1 inhibitor, 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) or recombinant IL-2 (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 treatment in another investigational device or drug study.

- Ending a treatment with an investigational drug or investigational device less than 3
months or 5 half-lives from the last dose of the investigational drug (whichever is
longer) at screening.

Minimum age: 18 Years
Maximum age: 75 Years
Sex: All

Further information on the trial in WHO primary registry

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

Further information on the trial from WHO database (ICTRP)

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

Further information on trial

Date trial registered

18.12.2020

Incorporation of the first participant

06.05.2021

Recruitment status

Recruiting

Global completion date of trial

30.11.-0001

Academic title (Data source: 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

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).

Phase (Data source: WHO)

Phase 2

Primary end point (Data source: WHO)

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

Secundary end point (Data source: WHO)

Change from Baseline in Lupus Quality of Life (QoL) Questionnaire Score
Change from Baseline in Medical Outcomes Short Form-36 Questionnaire Score
Change from Baseline in Patient-Reported Outcome Measurement Information System Fatigue Short Form 7a Instrument (PROMIS Fatigue SF 7A) Fatigue Score
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
Number of Participants who Experience a Clinically Significant Change in Laboratory Values and Vital Sign Measurements
Number of Participants who Experience a Treatment-Emergent Adverse Event (AE) and Serious Adverse Event (SAE)
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 Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) 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 Achieving a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24
Percent of Participants who Experience a Flare
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
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
Trough Serum and Sparse Postdose Serum Concentration of Efavaleukin Alfa

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Basel, St. Gallen

Countries (Data source: WHO)

Switzerland might not appear as site of trial if it has not yet been entered as such in the WHO primary registry.
Japan, Korea, Poland, Republic of, Turkey, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

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

Contact for general information (Data source: WHO)

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

Contact for scientific information (Data source: WHO)

MD
Amgen

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Amgen

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Ethikkommission Ostschweiz (EKOS)

Date of authorisation by the ethics committee

12.08.2021

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2021-00736

Secondary ID (Data source: WHO)

20200234