- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01369199
Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B (HBRN)
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
To determine the efficacy of treatment with 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon in the treatment of chronic hepatitis B in hepatitis B "e" antigen (HBeAg) positive adults who are in the immune tolerant phase.
To evaluate safety and sustained responses after treatment with entecavir and peginterferon alfa-2a in the treatment of chronic hepatitis B in HBeAg positive adults who are in the immune tolerant phase.
A single arm treatment study of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon alfa-2a in adults with HBeAg-positive chronic hepatitis B with normal or near normal alanine aminotransferase (ALT) levels and high serum levels of hepatitis B virus (HBV) DNA ("immune tolerant" HBeAg-positive chronic hepatitis B). All participants followed for 48 weeks after treatment discontinuation (week 96 for those who completed treatment).
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 3
Kontakter och platser
Studieorter
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California
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Los Angeles, California, Förenta staterna, 90095
- University of California Los Angeles
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Los Angeles, California, Förenta staterna, 90048
- Cedars Sinai Medical Center
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San Francisco, California, Förenta staterna, 94143
- University of California San Francisco
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San Francisco, California, Förenta staterna, 94115
- California Pacific Medical Center
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Hawaii
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Honolulu, Hawaii, Förenta staterna, 96813
- Queen's Medical Center
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Maryland
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Bethesda, Maryland, Förenta staterna, 20892
- NIH Clinical Center
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Massachusetts
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Boston, Massachusetts, Förenta staterna, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Förenta staterna, 02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, Förenta staterna, 48109
- University of Michigan Health System
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Minnesota
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Minneapolis, Minnesota, Förenta staterna, 55446
- University of Minnesota
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Rochester, Minnesota, Förenta staterna, 55905
- Mayo Clinic
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Missouri
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Saint Louis, Missouri, Förenta staterna, 63110
- Washington University
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Saint Louis, Missouri, Förenta staterna, 63104
- Saint Louis University
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North Carolina
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Chapel Hill, North Carolina, Förenta staterna, 27599
- University of North Carolina
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Durham, North Carolina, Förenta staterna, 27710
- Duke University Medical Center
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Texas
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Dallas, Texas, Förenta staterna, 75390
- University of Texas Southwestern
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Dallas, Texas, Förenta staterna, 75246
- Baylor University Medical Center
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Virginia
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Richmond, Virginia, Förenta staterna, 23498
- Virginia Commonwealth University
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Washington
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Seattle, Washington, Förenta staterna, 98101
- Virginia Mason Medical Center
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Seattle, Washington, Förenta staterna, 98105
- University of Washington Medical Center
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Ontario
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Toronto, Ontario, Kanada, M5T 2S8
- University of Toronto
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Enrolled in & completed the baseline evaluation for NCT01263587 or completed the necessary components of NCT01263587 by the end of baseline visit.
- >18 years of age at the baseline visit (day 0). Patients >50 years of age at baseline will need to have a liver biopsy as standard of care with hepatic activity index (HAI) ≤3 & Ishak fibrosis score ≤1 within 96 weeks prior to baseline visit.
- Documented chronic HBV infection as evidenced by detection of HBsAg in serum for ≥24 weeks prior to baseline visit OR at least one positive HBsAg & negative anti-hepatitis B core (HBc) immunoglobulin (IgM) within 24 weeks prior to baseline visit OR at least one positive HBsAg & two positive HBV DNA over a period of ≥24 weeks prior to baseline visit.
- Presence of HBeAg in serum at last screening visit within 6 weeks of baseline visit.
- Serum HBV DNA level >10˄7 IU/mL on at least two occasions at least 12 weeks apart during the 52 weeks before baseline visit. One of the two HBV DNA levels must be within 6 weeks of baseline visit.
- ALT levels persistently ≤45 U/L in males, ≤30 U/L in females (approx. 1.5 times the upper limit of normal (ULN) range) as documented by at least three values: one taken 28-52 weeks before baseline visit, one taken 6 to 24 weeks before the baseline visit, & the final value within 6 weeks prior to baseline visit.
- No evidence of hepatocellular carcinoma (HCC) based upon alpha-fetoprotein (AFP) ≤20 ng/mL at screening visit (up to 6 weeks prior to baseline visit). a. Participants who meet American Association for the Study of Liver Diseases (AASLD) criteria for HCC surveillance must have negative liver imaging as shown by ultrasound, computerized tomography (CT) or magnetic resonance imaging (MRI) within 28 weeks prior to baseline visit. b. Participants with AFP >20 ng/mL must be evaluated clinically with additional imaging & shown not to have HCC on CT or MRI before they can be enrolled.
Exclusion Criteria:
- History of hepatic decompensation
- Evidence of decompensated liver disease prior to or during screening, including direct bilirubin >0.5 mg/dL, international normalization ratio (INR) >1.5, or serum albumin <3.5 g/dL.
- Platelet count <120,000/mm3, hemoglobin <13 g/dL (males) or <12 g/dL (females), absolute neutrophil count < 1500 /mm3 (<1000/mm3 for African-Americans) at last screening visit.
- Previous treatment with medications that have established activity against HBV including interferon & nucleos(t)ide analogs ≥24 weeks. Patients with <24 weeks of prior HBV treatment & a wash-out period >24 weeks are not excluded.
- Known allergy or intolerance to study medications.
- Females who are pregnant or breastfeeding. Females of childbearing potential unable or unwilling to use a reliable method of contraception during the treatment period.
- Renal insufficiency with calculated creatinine clearance <50 mL/min at screening.
- History of alcohol or drug abuse within 48 weeks of baseline visit.
- Previous liver or other organ transplantation (including engrafted bone marrow).
- Any other concomitant liver disease, including hepatitis C or D. Non-alcoholic fatty liver disease (NAFLD) with steatosis &/or mild to moderate steatohepatitis is acceptable but NAFLD with severe steatohepatitis is exclusionary.
- Presence of anti-hepatitis D virus (HDV) or anti-hepatitis C virus (HCV) (unless HCV RNA negative) in serum on any occasion in the 144 weeks prior to baseline visit. Presence of anti-HIV (test completed within 6 weeks prior to baseline visit).
- Pre-existing psychiatric condition(s), including, but not limited to: current moderate or severe depression, history of depression requiring hospitalization within the past 10 years, history of suicidal or homicidal attempt within the past 10 years, history of severe psychiatric disorders as determined by a study physician.
- History of immune-mediated or cerebrovascular disease, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician.
- Any medical condition that would, in the opinion of a study physician, be predicted to be exacerbated by therapy or that would limit study participation.
- Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study.
- Evidence of active or suspected malignancy, or a history of malignancy within the 144 weeks prior to baseline visit (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).
- Expected need for ongoing use of any antivirals with activity against HBV during the course of the study.
- Concomitant use of complementary or alternative medications purported to have antiviral activity.
- Participation in any other clinical trial involving investigational drugs within 30 days of the baseline visit or intention to participate in another clinical trial involving investigational drugs during participation in this study.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: Peginterferon and entecavir
A combination of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon.
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Entecavir 0.5 mg daily orally for 48 weeks plus peginterferon 180 µg sq weekly during weeks 9-48 of treatment.
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Incidensen av allvarliga biverkningar (SAE) per person-år
Tidsram: Från första behandlingen till slutet av behandlingen (upp till 48 veckor) och slutet av uppföljningen (upp till 96 veckor)
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Incidensen beräknas som antalet SAE dividerat med antalet personår av observation, vilket är summan, för alla deltagare, av antalet år mellan behandlingens början och behandlingens slut, eller slutet av efterföljande -upp, respektive.
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Från första behandlingen till slutet av behandlingen (upp till 48 veckor) och slutet av uppföljningen (upp till 96 veckor)
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Proportion of Participants With HBeAg Loss (Lack of Detectable HBeAg) AND HBV DNA ≤1,000 IU/mL
Tidsram: End of follow-up (up to 96 weeks)
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Lack of data was considered to be treatment failure.
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End of follow-up (up to 96 weeks)
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Incidence of Adverse Events (AEs) Per Person-Year of Observation
Tidsram: From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
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The number of AEs includes both AEs and Serious Adverse Events (SAEs).
The incidence is calculated as the number of AEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.
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From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Andel deltagare med HBeAg Seroconversion
Tidsram: Behandlingsslut (upp till 48 veckor)
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Behandlingsslut (upp till 48 veckor)
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Andel deltagare med HBeAg Seroconversion
Tidsram: Slut på uppföljning (upp till 96 veckor)
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Slut på uppföljning (upp till 96 veckor)
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Andel deltagare med HBsAg Seroconversion
Tidsram: Slut på behandlingen (upp till 48 veckor)
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Slut på behandlingen (upp till 48 veckor)
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Andel deltagare med HBsAg Seroconversion
Tidsram: Slut på uppföljning (upp till 96 veckor)
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Slut på uppföljning (upp till 96 veckor)
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Andel deltagare med HBV-DNA ≤1000 IE/ml
Tidsram: Behandlingsslut (upp till 48 veckor)
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Behandlingsslut (upp till 48 veckor)
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Andel deltagare med HBV-DNA ≤1000 IE/ml
Tidsram: Slut på uppföljning (upp till 96 veckor)
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Slut på uppföljning (upp till 96 veckor)
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Proportion of Participants With HBeAg Loss
Tidsram: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBeAg Loss
Tidsram: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With HBsAg Loss
Tidsram: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBsAg Loss
Tidsram: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With Alanine Aminotransferase (ALT) <45 U/L for Men, <30 U/L for Women
Tidsram: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With ALT <45 U/L for Men, <30 U/L for Women
Tidsram: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)
Tidsram: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)
Tidsram: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With HBV DNA <20 IU/mL
Tidsram: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBV DNA <20 IU/mL
Tidsram: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Absence of Detectable Antiviral Drug-resistance HBV Mutations
Tidsram: End of treatment (up to 48 weeks)
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HBV drug resistance variant testing was performed at the CDC laboratory.
The sequences of the HBV polymerase spanning nucleotide positions 311-1021 were determined by Sanger sequencing.
Drug resistance mutations that were tested in this study included L80VI, L82M, T128N, W153Q, F166L, I169T, V173L, L180M, A181TV, T184ACFGILMS, V191T, A194T, A200V, S202ETV, M204IV, V207I, N236T, M250ILV, and G145R.
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End of treatment (up to 48 weeks)
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Samarbetspartners och utredare
Utredare
- Studiestol: Averell Sherker, MD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Huvudutredare: Anna Lok, MD, University of Michigan
Publikationer och användbara länkar
Användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Matsmältningssystemets sjukdomar
- RNA-virusinfektioner
- Virussjukdomar
- Infektioner
- Blodburna infektioner
- Smittsamma sjukdomar
- Leversjukdomar
- Hepatit, Viral, Human
- Hepadnaviridae-infektioner
- DNA-virusinfektioner
- Enterovirusinfektioner
- Picornaviridae-infektioner
- Hepatit, kronisk
- Hepatit B
- Hepatit
- Hepatit A
- Hepatit B, kronisk
- Anti-infektionsmedel
- Antivirala medel
- Peginterferon alfa-2a
- Entecavir
Andra studie-ID-nummer
- DK082864 HBRN IT Adult Trial
- UL1RR024986 (U.S.S. NIH-anslag/kontrakt)
- UL1TR001111 (U.S.S. NIH-anslag/kontrakt)
- U01DK082916 (U.S.S. NIH-anslag/kontrakt)
- U01DK082864 (U.S.S. NIH-anslag/kontrakt)
- U01DK082874 (U.S.S. NIH-anslag/kontrakt)
- U01DK082944 (U.S.S. NIH-anslag/kontrakt)
- U01DK082843 (U.S.S. NIH-anslag/kontrakt)
- U01DK082871 (U.S.S. NIH-anslag/kontrakt)
- UL1TR000004 (U.S.S. NIH-anslag/kontrakt)
- A-DK-3002-001 (Annat bidrag/finansieringsnummer: Interagency agreement with NIDDK)
- U01DK082863 (U.S.S. NIH-anslag/kontrakt)
- U01DK082866 (U.S.S. NIH-anslag/kontrakt)
- U01DK082867 (U.S.S. NIH-anslag/kontrakt)
- U01DK082872 (U.S.S. NIH-anslag/kontrakt)
- U01DK082919 (U.S.S. NIH-anslag/kontrakt)
- U01DK082923 (U.S.S. NIH-anslag/kontrakt)
- U01DK082927 (U.S.S. NIH-anslag/kontrakt)
- U01DK082943 (U.S.S. NIH-anslag/kontrakt)
- UL1TR000058 (U.S.S. NIH-anslag/kontrakt)
- P30DK050306 (U.S.S. NIH-anslag/kontrakt)
- M01RR000040 (U.S.S. NIH-anslag/kontrakt)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
Tidsram för IPD-delning
Kriterier för IPD Sharing Access
IPD-delning som stöder informationstyp
- STUDY_PROTOCOL
- SAV
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Studerar en amerikansk FDA-reglerad produktprodukt
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-
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