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SNCTP000003907 | NCT03719313 | BASEC2019-01466

Eine klinische Studie zur Beurteilung der Wirksamkeit und Sicherheit des Prüfmedikaments Lonafarnib bei gleichzeitiger Gabe mit Ritonavir bei Patienten mit chronischer Infektion mit dem Hepatitis-Delta-Virus, die eine Anti-HBV-Langzeittherapie mit Nukleos(t)iden erhalten (D-LIVR)

Data source: BASEC (Imported from 25.09.2020), WHO (Imported from 20.09.2020)
Changed: 16.09.2020
Disease category: Infections and Infestations

Brief description of trial (Data source: BASEC)

In der D-LIVR-Studie werden das Wirksamkeits- und Sicherheitsprofil des Prüfmedikaments bei Menschen mit einer chronischen Infektion mit dem Hepatitis-Delta-Virus (HDV) beurteilt. Die Studie besteht aus einem Vorabuntersuchungsabschnitt (bis zu 6 Monate bzw. bis zu 45 Tage), einem Behandlungsabschnitt (etwa 48 Wochen) und einem Nachbeobachtungsabschnitt (etwa 24 Wochen). Die Studie umfasst 25 Besuchstermine über einem Zeitraum von 24 Monaten.

Die Studienteilnehmer werden nach dem Zufallsprinzip 1 von 4 Gruppen zugeordnet, die das Prüfmedikament erhalten. Zwei Gruppen erhalten das Prüfmedikament als ein ausschließlich oral einzunehmendes Medikament und die beiden anderen Gruppen erhalten ein oral einzunehmendes Prüfmedikament sowie ein injizierbares Prüfpräparat. Weder der Studienteilnehmer noch das Studienteam wissen, welche Behandlung ein Studienteilnehmer erhält.

Das primäre Ziel der Studie besteht darin, die Wirkung von Lonafarnib/Ritonavir im Vergleich zu einem Placebo (Scheinbehandlung) bei Studienteilnehmern zu beurteilen.

Es werden voraussichtlich weltweit bis zu 400 Patienten mit chronischer HDV an dieser Studie teilnehmen.

Health conditions investigated (Data source: BASEC)

Hepatitis-Delta-Virus (HDV)

Health conditions (Data source: WHO)

Hepatitis Delta Virus

Rare disease (Data source: BASEC)

Yes

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

Lonafarnib: Prüfmedikament, zwei Kapseln zweimal täglich
Norvir® (Ritonavir): zugelassenes Medikament, eine Tablette zweimal täglich
Pegasys® (Peginterferon alfa-2a): in vielen Ländern zugelassen, Injektion einmal wöchentlich
Placebo Lonafarnib: zwei Kapseln zweimal täglich
Placebo Norvir® (Ritonavir): eine Tablette zweimal täglich

Interventions (Data source: WHO)

Drug: Lonafarnib;Drug: Ritonavir;Drug: PEG IFN-alfa-2a;Drug: Placebo Lonafarnib;Drug: Placebo Ritonavir

Criteria for participation in trial (Data source: BASEC)

• männliche und weibliche Patienten im Alter von mindestens 18 Jahren
• chronische HDV
• nachweisliche Unterdrückung der DNA des Hepatitis-B-Virus (< 20 IE/ml) nach einer
mindestens 12-wöchigen Behandlung mit den Anti-HBV-Nukleos(t)iden Entecavir oder
Tenofovir vor der Einleitung der Prüfbehandlung

Exclusion criteria (Data source: BASEC)

• vorherige Einnahme von Lonafarnib innerhalb von 12 Monaten vor dem Vorabuntersuchungs- bzw. dem Voruntersuchungsabschnitt
oder während der Studie
• Infektion mit dem Hepatitis-A-, Hepatitis-C- oder Hepatitis-E-Virus
• Humanes Immunschwäche-Virus (HIV)

Inclusion/Exclusion Criteria (Data source: WHO)


Inclusion Criteria:

1. Chronic HDV infection for at least 6 months in duration, documented by a positive HDV
antibody test and HDV RNA = 500 IU/mL.

Note: All genotypes of HDV permitted.

2. Demonstrable suppression of HBV DNA following at least 12 weeks of anti-HBV
nucleos(t)ide treatment with entecavir or tenofovir prior to initiating therapy.

3. Serum ALT > 1.3 x upper limit of the normal range (ULN) and < 10 x ULN.

4. Baseline liver biopsy demonstrating evidence of chronic hepatitis.

5. ECGs demonstrating no acute ischemia or clinically significant abnormality.

6. Normal dilated retinal examination.

Exclusion Criteria:

General Exclusions

1. Previous use of LNF within 12 months.

2. Current or previous history of decompensated liver disease.

3. Co-infected with human immunodeficiency virus or hepatitis C virus (HCV) by detectable
HIV RNA and HCV RNA, respectively.

4. Evidence of significant portal hypertension.

5. Current evidence or history of ascites requiring diuretics or paracentesis, or hepatic
encephalopathy.

6. History of hepatocellular carcinoma.

7. Patients with any of the following:

- Current eating disorder

- Evidence of alcohol substance use disorder.

- Drug abuse within the previous 6 months before screening.

8. Prior history or current evidence of any of the following:

- Immunologically mediated disease,

- Retinal disorder or clinically relevant ophthalmic disorder,

- Any malignancy within 5 years before screening,

- Cardiomyopathy or significant ischemic cardiac or cerebrovascular disease,

- Chronic pulmonary disease,

- Pancreatitis or colitis,

- Severe or uncontrolled psychiatric disorder.

9. Other significant medical condition that may require intervention during the study.

10. Any condition that may impact proper absorption.

11. Therapy with an immunomodulatory agent, IFN-a (eg, IFN alfa-2a or IFN-alfa-2b, or
pegylated IFN-alfa-2a or alfa 2b), cytotoxic agent, or chronic systemic
corticosteroids within 12 months of screening.

12. Use of heparin or warfarin.

13. Systemic antibiotics, antifungals, or antivirals for treatment of active infection
other than HBV.

14. Receipt of systemic immunosuppressive therapy.

15. History or evidence for any intolerance or hypersensitivity to LNF, RTV, PEG
IFN-alfa-2a, tenofovir or entecavir.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03719313

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03719313

Further information on trial

Date trial registered

18.10.2018

Incorporation of the first participant

01.12.2018

Recruitment status

Recruiting

Academic title (Data source: WHO)

A Phase 3, Matrix Design, Partially Double-Blind, Randomized Study of the Efficacy and Safety of 50 mg Lonafarnib/100 mg Ritonavir BID With and Without 180 mcg PEG IFN-alfa-2a for 48 Weeks Compared With PEG IFN-alfa-2a Monotherapy and Placebo Treatment in Patients Chronically Infected With Hepatitis Delta Virus Being Maintained on Anti-HBV Nucleos(t)Ide Therapy (D-LIVR)

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)

To compare the composite virologic and biochemical response rate at end-of-treatment (EOT) in patients who receive LNF 50 mg/RTV 100 mg BID vs patients who receive placebo.;To compare the composite virologic and biochemical response rate at EOT in patients who receive LNF 50 mg/RTV 100 mg BID with PEG IFN-alfa-2a 180 mcg QW vs patients who receive placebo.

Secundary end point (Data source: WHO)

To compare the histologic response rate at EOT in patients who receive LNF 50 mg/RTV 100 mg BID vs patients who receive placebo.;To compare the histologic response rate at EOT in patients who receive LNF 50 mg/RTV 100 mg BID with PEG IFN-alfa-2a 180 mcg QW vs patients who receive placebo.;To evaluate the health-related quality of life (HRQL) over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID vs placebo.;To evaluate the HRQL over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID/PEG IFN-alfa-2a 180 mcg QW vs placebo.;To evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID vs placebo.;To evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] over a 48-week treatment period in patients who receive LNF 50 mg/RTV 100 mg BID/PEG IFN-alfa-2a 180 mcg QW vs placebo.

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)

Bern

Countries (Data source: WHO)

Belgium, Bulgaria, Canada, France, Germany, Greece, Israel, Italy, Moldova, Mongolia, New Zealand, Pakistan, Republic of, Romania, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States, Vietnam

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Marco Pecora
+4161270832
StartupSwitzerland@IQVIA.com

Contact for general information (Data source: WHO)

Sue Speyer
650-272-6138
DLIVR@eigerbio.com

Contact for scientific information (Data source: WHO)

Sue Speyer
650-272-6138
DLIVR@eigerbio.com

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Eiger BioPharmaceuticals

Authorisation by the ethics committee (Data source: BASEC)

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

Kantonale Ethikkommission Bern

Date of authorisation by the ethics committee

13.05.2020

Further trial identification numbers

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

2019-01466

Secondary ID (Data source: WHO)

EIG-LNF-011