Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda

Liver Disease

Hepatitis D

Peg-interferon Lambda is a covalent conjugate of human recombinant non- pegylated IFN lambda and a 20-kDa linear PEG chain.

Peg-interferon lambda

Lonafarnib

Ritonavir

National Institutes of Health Clinical Center

Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon

Decline of HDV RNA viral titer of >2 logs from baseline at 24 weeks of therapy

Discontinuation of the medication before 24 weeks by the clinical team or patient will be considered a failure to tolerate the medicine.

Undetectable HDV RNA at both 12 and 24 weeks post treatment follow-up visits

Reduction in histologic inflammatory scores (modified HAI) by at leasttwo points with no progression in histologic fibrosis (Ishak) at week 24 post-treatment follow-up.

Normalization of serum ALT (ALT <20 in females and ALT <31 in males) at the end of therapy, at week 12 of posttherapy follow-up and at week 24 of post-therapy follow-up, OR reduction in serum ALT by >50% of baseline at week 12 of post therapy follow up and week 24 of post therapy follow up.

Reduction in hepatic venous pressure gradient (HVPG) measurements by >25% of baseline OR normalization of HVPG (<5 mm Hg) at end of therapy.

Reduction in Fibroscan transient elastography values by >25% of baseline at end of therapy.

Loss of HBsAg from the serum at 12 weeks after completing therapy

Loss of HBsAg from the serum at 24 weeks after completing therapy

Change in quantitative HBsAg levels at from baseline to week 24

Change in quantitative HBsAg levels at from baseline to 24 weeks after completing therapy

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lonafarnib/Ritonavir at 50 mg/100 mg daily for 24 weeks followed by 24 weeks of off therapy follow-up.

Lonafarnib/Ritonavir at 75 mg/100 mg daily for 24 weeks followed by 24 weeks of off therapy follow-up.

Lonafarnib/Ritonavir at 100 mg/100 mg daily for 24 weeks followed by 24 weeks of off therapy follow-up.

Placebo for 12 weeks then Lonafarnib/Ritonavir at 50 mg/100 mg daily for 12 weeks followed by 24 weeks of off therapy follow-up.

Placebo for 12 weeks then Lonafarnib/Ritonavir at 75 mg/100 mg daily for 12 weeks followed by 24 weeks of off therapy follow-up.

Placebo for 12 weeks then Lonafarnib/Ritonavir at 100 mg/100 mg daily for 12 weeks followed by 24 weeks of off therapy follow-up.

Lonafarnib/Ritonavir at 50 mg/100 mg daily for 24 weeks followed by 24 weeks of off therapy follow-up.
Lonafarnib: prenylation inhibitor to be administered daily at doses of 50 mg, 75 mg or 100 mg.
Ritonavir: FDA approved drug for use of boosting other drugs. Will be used to boost ritonavir as they both use the same CYP system. Will be administered at 100 mg daily.

50mg/100mg Lonafarnib/Ritonavir

Lonafarnib/Ritonavir at 75 mg/100 mg daily for 24 weeks followed by 24 weeks of off therapy follow-up.
Lonafarnib: prenylation inhibitor to be administered daily at doses of 50 mg, 75 mg or 100 mg.
Ritonavir: FDA approved drug for use of boosting other drugs. Will be used to boost ritonavir as they both use the same CYP system. Will be administered at 100 mg daily.

75mg/100mg Lonafarnib/Ritonavir

Lonafarnib/Ritonavir at 100 mg/100 mg daily for 24 weeks followed by 24 weeks of off therapy follow-up.
Lonafarnib: prenylation inhibitor to be administered daily at doses of 50 mg, 75 mg or 100 mg.
Ritonavir: FDA approved drug for use of boosting other drugs. Will be used to boost ritonavir as they both use the same CYP system. Will be administered at 100 mg daily.

100mg/100mg Lonafarnib/Ritonavir

Placebo for 12 weeks then Lonafarnib/Ritonavir at 50 mg/100 mg daily for 12 weeks followed by 24 weeks of off therapy follow-up.
Lonafarnib: prenylation inhibitor to be administered daily at doses of 50 mg, 75 mg or 100 mg.
Ritonavir: FDA approved drug for use of boosting other drugs. Will be used to boost ritonavir as they both use the same CYP system. Will be administered at 100 mg daily.
Placebo: Placebo

Placebo Then 50 mg/100 mg Lonafarnib/Ritonavir

Placebo for 12 weeks then Lonafarnib/Ritonavir at 75 mg/100 mg daily for 12 weeks followed by 24 weeks of off therapy follow-up.
Lonafarnib: prenylation inhibitor to be administered daily at doses of 50 mg, 75 mg or 100 mg.
Ritonavir: FDA approved drug for use of boosting other drugs. Will be used to boost ritonavir as they both use the same CYP system. Will be administered at 100 mg daily.
Placebo: Placebo

Placebo Then 75mg/100mg Lonafarnib/Ritonavir

Placebo for 12 weeks then Lonafarnib/Ritonavir at 100 mg/100 mg daily for 12 weeks followed by 24 weeks of off therapy follow-up.
Lonafarnib: prenylation inhibitor to be administered daily at doses of 50 mg, 75 mg or 100 mg.
Ritonavir: FDA approved drug for use of boosting other drugs. Will be used to boost ritonavir as they both use the same CYP system. Will be administered at 100 mg daily.
Placebo: Placebo

Placebo Then 100mg/100mg Lonafarnib/Ritonavir

Total

Sex: Female, Male

Race/Ethnicity, Customized

The number of participants who experienced a > 2 log IU/mL decline in serum HDV RNA at 12 weeks of treatment

Number of Participants With Decline of Hepatitis Delta Virus (HDV) RNA Quantitative Measurements of >2 Logs From Baseline at 12 Weeks of Treatment

The number of participants who experienced a > 2 log IU/mL decline in serum HDV RNA levels at 24 weeks of treatment

Number of Participants With Decline of HDV RNA Quantitative Measurement of > 2 Logs From Baseline at 24 Weeks of Treatment

Lonafarnib/Ritonavir at 50 mg/100 mg daily for 24 weeks followed by 24 weeks of off therapy follow-up.
Lonafarnib: prenylation inhibitor to be administered daily at doses of 50 mg, 75 mg or 100 mg.
Ritonavir: FDA approved drug for use of boosting other drugs. Will be used to boost ritonavir as they both use the same cytochrome p450 (CYP) system. Will be administered at 100 mg daily.

Treatment

Post-treatment Follow-up

Christopher Koh, MD

Lonafarnib/Ritonavir at 50 mg/100 mg daily for 24 weeks.

24 Weeks of 50mg/100mg Lonafarnib/Ritonavir

Lonafarnib/Ritonavir at 75 mg/100 mg daily for 24 weeks.

24 Weeks of 75mg/100mg Lonafarnib/Ritonavir

Lonafarnib/Ritonavir at 100 mg/100 mg daily for 24 weeks.

24 Weeks of 100mg/100mg Lonafarnib/Ritonavir

12 Weeks of Placebo

Lonafarnib/Ritonavir at 50 mg/100 mg daily for second 12 weeks.

12 Weeks of 50 mg/100 mg Lonafarnib/Ritonavir

Lonafarnib/Ritonavir at 75 mg/100 mg daily for second 12 weeks.

12 Weeks of 75mg/100mg Lonafarnib/Ritonavir

Lonafarnib/Ritonavir at 100 mg/100 mg daily for second 12 weeks.

12 Weeks of 100mg/100mg Lonafarnib/Ritonavir

prenylation inhibitor to be administered daily at doses of 50 mg, 75 mg or 100 mg.

FDA approved drug for use of boosting other drugs. Will be used to boost Lonafarnib as they both use the same cytochrome P450 system. Will be administered at 100 mg daily.

hepatitis d/protease

Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon

Treatment of Chronic Delta Hepatitis With Lonafarnib and Ritonavir

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