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SNCTP000003557 | NCT03744910 | BASEC2019-01145

Studie zur Bewertung der Wirksamkeit und Sicherheit der Behandlung des Prüfmedikaments Clazakizumab im Vergleich zu einem Placebo (inaktive Substanz) bei Empfängern von Nierentransplantationen mit chronisch aktiver Antikörper-vermittelter Abstoßung (CABMR)

Data source: BASEC (Imported from 27.01.2022), WHO (Imported from 18.01.2022)
Changed: 19.10.2021
Disease category: Other

Brief description of trial (Data source: BASEC)

Ziel dieser Studie ist es, die Wirksamkeit und Sicherheit der Behandlung mit Clazakizumab im Vergleich zu einem Placebo (inaktive Substanz) bei Empfängern von Nierentransplantationen mit CABMR zu untersuchen. In der Studie wird untersucht, ob Clazakizumab den Funktionsverlust der transplantierten Niere verlangsamen oder verhindern und den Zeitraum verlängern kann, bevor die Patienten wieder zur Dialyse gehen oder eine neue Niere bekommen müssen.

Clazakizumab oder das Placebo wird alle 4 Wochen subkutan (Injektionen unter die Haut) verabreicht.

Die Studie wird aus folgenden Behandlungsperioden bestehen:
- Das Screening-Verfahren beträgt bis zu 6 Wochen. Der Screening-Besuch besteht aus einer Bewertung, um festzustellen, ob die Patienten alle Zulassungsvoraussetzungen für die Teilnahme an der Studie erfüllen.
- Die Behandlungsdauer beträgt bis zu 260 Wochen, wobei die Patienten alle 4 Wochen eine subkutane Injektion (entweder Clazakizumab 12,5 mg / ml oder Placebo 1 ml) erhalten.
- Die Nachbeobachtungszeit beträgt bis zu 5 Monaten nach der letzten Dosis des Prüfpräparats.
Die maximale Studiendauer für einen einzelnen Patienten beträgt ca. 5,5 Jahre.

Health conditions investigated (Data source: BASEC)

Behandlung einer chronisch aktiven Antikörper-vermittelten Abstoßung bei Patienten mit Nierentransplantationen

Health conditions (Data source: WHO)

Antibody-mediated Rejection

Rare disease (Data source: BASEC)

No

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

Die Patienten werden nach dem Zufallsprinzip ausgewählt und erhalten entweder:
Clazakizumab 12,5 mg / ml SC-Injektion einmal alle 4 Wochen für bis zu 260 Wochen oder bis zum Verlust des Allotransplantats oder Tod
oder
- Placebo-1-ml-SC-Injektion alle 4 Wochen bis zu 260 Wochen oder bis zum Verlust des Allotransplantats oder Tod
- Die Patienten müssen auch eine prophylaktische Behandlung (orales Trimethoprim / Sulfamethoxazol 80 mg als Trimethoprim täglich oder 160 mg als Trimethoprim x 3 pro Woche) für PJP (Pneumocystis jiroveci pneumonia) vom Screening-Termin bis einschließlich Woche 52 einnehmen alternative prophylaktische PJP-Therapie beim Screening Sie können nach Ermessen des Prüfarztes verbleiben oder wenn die derzeitige Therapie nicht geeignet ist, sollte Trimethoprim / Sulfamethoxazol mindestens 1 Woche vor V2 begonnen werden. Für den Rest der Studie (> Woche 52) sollte die PJP-Prophylaxe nach Ermessen des Prüfarztes fortgesetzt werden.

Interventions (Data source: WHO)

Biological: Clazakizumab;Drug: Physiologic saline solution

Criteria for participation in trial (Data source: BASEC)

1. Alter 18-70 Jahre
2. Empfänger von Lebendspender- / verstorbenen Spendernierentransplantaten ≥ 6 Monate ab dem Zeitpunkt
der Transplantation
3. Diagnose von CABMR (gemäß den diagnostischen Kriterien von Banff 2015)

Exclusion criteria (Data source: BASEC)

1. eGFR <25 mL/min/1.73 m2 or >65 mL/min/1.73 m2 (MDRD4)
2. Vorgeschichte von Magen - Darm - Perforationen, Divertikelerkrankungen oder Divertikulitis oder entzündliche Darmerkrankung
3. Aktive Infektionen, die systemische antimikrobielle Wirkstoffe erfordern und sind ungelöst vor dem Screening

Inclusion/Exclusion Criteria (Data source: WHO)


- Inclusion criteria:

1. Age 18-70 years.

2. Living donor/deceased donor kidney transplant recipients =6 months from time of
transplant.

3. Diagnosis of CABMR determined by kidney biopsy and the presence of HLA DSA using
single-antigen bead-based assays.

NOTE: If conducted within 6 months (+3 weeks) of the start of the screening
period, the biopsy and DSA analysis do not need to be repeated at screening. To
be considered for determination of study eligibility, the biopsy and DSA analysis
must be performed at least 2 months ± 2 weeks after the end of any prior
treatment for ABMR (including CABMR) or TCMR, in order to show continuing CABMR
and presence of HLA DSA. In addition, treatments for ABMR or TCMR are not allowed
within 3 months of the start of screening.

The following histopathologic and serologic diagnostic criteria (based on Banff
2015 criteria [Loupy et al, 2017]) must be met for inclusion:

- Morphologic evidence of chronic tissue injury, as demonstrated by TG (cg>0).
Biopsies without evidence of chronic tissue injury on light microscopy, but
with glomerular basement membrane double contours on electron microscopy
(cg1a) are eligible.

- Evidence of current/recent antibody interaction with vascular endothelium,
including 1 or more of the following.

- Linear C4d staining in peritubular capillaries or medullary vasa recta (C4d2
or C4d3 by immunofluorescence on frozen sections, or C4d > 0 by
immunohistochemistry on paraffin sections).

- At least moderate microvascular inflammation ([g + ptc] = 2) in the absence
of recurrent or de novo glomerulonephritis, although in the presence of
acute TCMR, borderline infiltrate, or infection, ptc = 2 alone is not
sufficient and g must be = 1.

NOTE: The local pathologist's diagnosis must be reviewed by a central pathologist
to confirm eligibility for entry into the study. Biopsies with other
histopathologic changes (eg, BKV nephropathy or recurrent glomerulonephritis) may
be eligible if concurrent CABMR changes (as detailed above) are present and
determined to be the predominant cause of renal dysfunction.

4. Serologic evidence of circulating DSA to HLA. NOTE: The local laboratory DSA
results must be reviewed and confirmed by the central HLA reviewer during the
screening period.

- Exclusion criteria:

1. Multi-organ transplant recipient (except for simultaneous kidney-pancreas or
previous multiple kidney transplants) or cell transplant (islet, bone marrow,
stem cell) recipient.

2. Treatment for ABMR (including CABMR) or TCMR within 3 months of the start of
screening.

3. Received T cell depleting agents (e.g., alemtuzumab, anti-thymocyte globulin)
within 3 months of the start of screening.

4. Pregnant, breastfeeding, or unwillingness to practice adequate contraception.

5. History of active tuberculosis (TB).

6. History of human immunodeficiency virus (HIV) infection or positive for HIV.

7. Seropositive for hepatitis B surface antigen (HBsAg)

8. Hepatitis C virus (HCV) RNA positive.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03744910

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT03744910

Further information on trial

Date trial registered

06.11.2018

Incorporation of the first participant

14.10.2019

Recruitment status

Recruiting

Academic title (Data source: WHO)

A Pivotal Phase 3 Trial to Evaluate the Safety and Efficacy of Clazakizumab for the Treatment of Chronic Active Antibody-mediated Rejection in Kidney Transplant Recipients

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

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

Phase (Data source: WHO)

Phase 3

Primary end point (Data source: WHO)

Time to all-cause composite allograft loss

Secundary end point (Data source: WHO)

Time of maximum serum concentration (Tmax, Tmax ss) of CSL300;Area under the concentration-time curve (AUC0-tau) at steady state of CSL300;Trough serum concentrations (Ctrough, Ctrough ss) of CSL300;Maximum serum concentration (Cmax, Cmax ss) of CSL300;Overall patient survival;Change in Banff lesion grading score (2015 criteria) of pre-treatment to post-treatment (Week 52) kidney biopsies;Incidence of acute rejection episodes of T cell-mediated rejection(TCMR) and Antibody-mediated rejection (ABMR) from Baseline to EOT;Change in (Donor-specific antibodies) DSA titers and Mean fluorescence intensity (MFI) scores from Baseline to EOT;Change in spot urine albumin creatinine ratio (UACR) from Baseline to EOT;Change in mean estimated glomerular filtration rate (eGFR) from Baseline to End of Treatment (EOT);Incidence and time to death-censored allograft loss

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)

Zurich

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.
Australia, Canada, Czechia, France, Germany, Hungary, Netherlands, Spain, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Prof. Dr. Thomas Müller
+41 44 255 27 75
Thomas.Mueller@usz.ch

Contact for general information (Data source: WHO)

Study Director;Trial Registration Coordinator
CSL Behring
610-878-4000
clinicaltrials@cslbehring.com

Contact for scientific information (Data source: WHO)

Study Director;Trial Registration Coordinator
CSL Behring
610-878-4000
clinicaltrials@cslbehring.com

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

CSL Behring

Additional sponsors (Data source: WHO)

ICON Clinical Research

Authorisation by the ethics committee (Data source: BASEC)

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

Kantonale Ethikkommission Zürich

Date of authorisation by the ethics committee

03.12.2019

Further trial identification numbers

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

2019-01145

Secondary ID (Data source: WHO)

2018-003682-34
VKTX01
CSL300_3001