Trial Outcomes & Findings for Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon (NCT NCT03600714)

NCT ID: NCT03600714

Last Updated: 2021-12-14

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 26 participants
• Primary outcome timeframe: Baseline and 24 weeks
• Results posted on: 2021-12-14

Participant Flow

Participant milestones

Measure	Treatment Patients were treated with lonafarnib 50 mg orally twice daily, ritonavir 100 mg orally twice daily and lambda 180 mcg subcutaneously weekly for 24 weeks
Overall Study STARTED	26
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Treatment Patients were treated with lonafarnib 50 mg orally twice daily, ritonavir 100 mg orally twice daily and lambda 180 mcg subcutaneously weekly for 24 weeks
Overall Study Out of country and could not return for post-treatment visits	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treatment n=26 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Age, Continuous	42 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	14 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants
Body mass index	27.3 kg/m^2 STANDARD_DEVIATION 8.9 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: Three participants who discontinued treatment before 24 weeks did not have HDV RNA measured at 24 weeks. They were seen at post-treatment visits

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

Outcome measures

Measure	Treatment n=23 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Number of Participants With Decline of Hepatitis D Virus (HDV) RNA Viral Titer of >2 Logs	18 Participants

PRIMARY outcome

Timeframe: 24 weeks

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

Outcome measures

Measure	Treatment n=26 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Number of Participants Who Discontinue Medication	3 Participants

SECONDARY outcome

Timeframe: 12 and 24 weeks after completing therapy

Population: 25 participants had data at 24 weeks post treatment

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

Outcome measures

Measure	Treatment n=25 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Number of Participants With Sustained Virologic Response	3 Participants

SECONDARY outcome

Timeframe: End of treatment and 24 weeks after completing therapy.

Population: 21 participants had liver biopsies at 24 weeks post treatment

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

Outcome measures

Measure	Treatment n=21 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Number of Participants With Reduction in Histologic Inflammatory Scores (Modified HAI)	6 Participants

SECONDARY outcome

Timeframe: End of therapy, and 12 and 24 weeks after completing therapy

Population: Two participants did not have ALT measures at 12 weeks post treatment

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.

Outcome measures

Measure	Treatment n=24 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Number of Participants With Normalization of Serum ALT	2 Participants

SECONDARY outcome

Timeframe: Baseline and 24 weeks after completing therapy

Population: Five participant did not have HVPG measured at 24 weeks post treatment

Reduction in hepatic venous pressure gradient (HVPG) measurements by >25% of baseline OR normalization of HVPG (<5 mm Hg) at 24 weeks after completing therapy

Outcome measures

Measure	Treatment n=21 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Number of Participants With Reduction of Hepatic Venous Pressure Gradient (HVPG)	10 Participants

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Only 13 participants had Fibroscans at baseline and 24 weeks

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

Outcome measures

Measure	Treatment n=13 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Number of Participants With Reduction in Fibroscan Transient Elastography Values	4 Participants

SECONDARY outcome

Timeframe: Week 24

Population: 22 participants had HBsAg values at week 24

Loss of HBsAg from the serum at week 24

Outcome measures

Measure	Treatment n=22 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Number of Participants With Loss of HBsAg at Week 24	0 Participants

SECONDARY outcome

Timeframe: 12 weeks after completing therapy

Population: 24 participants had HBsAg measurements at 12 weeks after the end of treatment

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

Outcome measures

Measure	Treatment n=24 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Number of Participants With Loss of HBsAg at Week 12 Weeks After Completing Therapy	0 Participants

SECONDARY outcome

Timeframe: 24 weeks after completing therapy

Population: 24 participants had HBsAg measurements at 24 weeks after the end of treatment

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

Outcome measures

Measure	Treatment n=24 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Number of Participants With Loss of HBsAg at 24 Weeks After Completing Therapy	0 Participants

SECONDARY outcome

Timeframe: Baseline and week 24

Population: 22 participants had HBsAg values at week 24

Change in quantitative log HBsAg levels at from baseline to week 24

Outcome measures

Measure	Treatment n=22 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Change in Quantitative Log HBsAg Levels From Baseline to Week 24	0.15 log IU/mL Standard Deviation 0.22

SECONDARY outcome

Timeframe: Baseline and 24 weeks after completing therapy

Population: 24 participants had HBsAg measurements at 24 weeks after the end of treatment

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

Outcome measures

Measure	Treatment n=24 Participants Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Change in Quantitative Log HBsAg Levels From Baseline 24 Weeks After Completing Therapy	0.16 log IU/mL Standard Deviation 0.19

Adverse Events

Treatment

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment n=26 participants at risk Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda
Gastrointestinal disorders Nausea	69.2% 18/26 • 48 Weeks
Gastrointestinal disorders Diarrhea	80.8% 21/26 • 48 Weeks
Metabolism and nutrition disorders Decreased Appetite	50.0% 13/26 • 48 Weeks
Gastrointestinal disorders GERD	57.7% 15/26 • 48 Weeks
Musculoskeletal and connective tissue disorders Fatigue	30.8% 8/26 • 48 Weeks
Nervous system disorders Headache	3.8% 1/26 • 48 Weeks
Investigations Weight Loss	23.1% 6/26 • 48 Weeks
Skin and subcutaneous tissue disorders Acneiform Rash	15.4% 4/26 • 48 Weeks
Hepatobiliary disorders Hyperbilirubinemia	23.1% 6/26 • 48 Weeks
Hepatobiliary disorders Ascites	3.8% 1/26 • 48 Weeks
Blood and lymphatic system disorders Anemia	7.7% 2/26 • 48 Weeks
Nervous system disorders Insomnia	7.7% 2/26 • 48 Weeks
Skin and subcutaneous tissue disorders Hair Loss	7.7% 2/26 • 48 Weeks
Metabolism and nutrition disorders Hypokalemia	3.8% 1/26 • 48 Weeks

Additional Information

Dr. Christopher Koh

NIDDK

Phone: 301-443-9402

Email: kohchris@mail.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place