Trial Outcomes & Findings for Effect of Insulin Resistance on the Safety and Efficacy of Pegylated Interferon and Ribavirin Treatment in HCV (Study P05562) (NCT NCT00705224)

NCT ID: NCT00705224

Last Updated: 2015-07-01

Results Overview

Sustained Virological response (SVR) was assessed at the end of the study (Visit 4) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma hepatitis C virus RNA (HCV-RNA) at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively.

• Recruitment status: COMPLETED
• Target enrollment: 250 participants
• Primary outcome timeframe: 24 weeks following completion of 24 or 48 weeks of therapy
• Results posted on: 2015-07-01

Participant Flow

Participant milestones

Measure	Pegylated Interferon and Ribavirin Naïve patients with chronic hepatitis C (CHC) of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on hepatitis C virus (HCV) genotype, viral load, activity and stage of hepatitis C.
Overall Study STARTED	250
Overall Study COMPLETED	239
Overall Study NOT COMPLETED	11

Reasons for withdrawal

Measure	Pegylated Interferon and Ribavirin Naïve patients with chronic hepatitis C (CHC) of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on hepatitis C virus (HCV) genotype, viral load, activity and stage of hepatitis C.
Overall Study Adverse Event	1
Overall Study Lack of Efficacy	2
Overall Study Withdrawal by Subject	3
Overall Study Lost to Follow-up	5

Baseline Characteristics

Effect of Insulin Resistance on the Safety and Efficacy of Pegylated Interferon and Ribavirin Treatment in HCV (Study P05562)

Baseline characteristics by cohort

Measure	Pegylated Interferon and Ribavirin n=250 Participants Naïve patients with CHC of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.
Age, Continuous	36.0 years STANDARD_DEVIATION 9.78 • n=5 Participants
Sex: Female, Male Female	104 Participants n=5 Participants
Sex: Female, Male Male	146 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Completer set for the primary analysis included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study.

Sustained Virological response (SVR) was assessed at the end of the study (Visit 4) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma hepatitis C virus RNA (HCV-RNA) at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively.

Outcome measures

Measure	Pegylated Interferon and Ribavirin n=223 Participants Naïve patients with CHC of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.	HOMA-IR >3 Subgroup of naïve patients with CHC of any genotype and a presence of insulin resistance at baseline treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.
Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study	81.2 Percentage of Participants Interval 76.0 to 86.3	—

SECONDARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Completer set for the primary analysis (N=223) included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study. Of the 223 participants in this population, 181 achieved SVR (N=140 and N=40) and were therefore included in this analysis. 1 participant of the 181 had missing values.

SVR was assessed at the end of the study (Visit 4) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as Homeostasis model assessment - of insulin-resistance [HOMA-IR] >3) to investigate the presence or absence of SVR. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of treatment. Visit 4 was considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively.

Outcome measures

Measure	Pegylated Interferon and Ribavirin n=140 Participants Naïve patients with CHC of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.	HOMA-IR >3 n=40 Participants Subgroup of naïve patients with CHC of any genotype and a presence of insulin resistance at baseline treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.
Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype I	45.7 Percentage of Participants	47.5 Percentage of Participants
Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype II	14.3 Percentage of Participants	7.5 Percentage of Participants
Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype III	38.6 Percentage of Participants	45.0 Percentage of Participants
Percentage of Participants Who Achieved Sustained Virological Response as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline Other	1.4 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Timeframe: Week 24 or 48 after treatment start

Population: Completer set for the primary analysis (N=223) included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study. Of the 223 participants in this population, 208 achieved RFT (N=156 and N=51) and were therefore included in this analysis. 1 participant of the 208 had missing values.

Response following treatment (RFT) was assessed at the end of treatment (Visit 3) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR >3) to investigate the presence or absence of RFT. RFT was defined as undetectable plasma HCV-RNA at end of treatment. Visit 3 was considered Week 24 or Week 48 after treatment start depending on treatment duration.

Outcome measures

Measure	Pegylated Interferon and Ribavirin n=156 Participants Naïve patients with CHC of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.	HOMA-IR >3 n=51 Participants Subgroup of naïve patients with CHC of any genotype and a presence of insulin resistance at baseline treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.
Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype III	35.9 Percentage of Participants	41.2 Percentage of Participants
Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype I	50.6 Percentage of Participants	52.9 Percentage of Participants
Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype II	12.2 Percentage of Participants	5.9 Percentage of Participants
Percentage of Participants Who Achieved Response Following Treatment as Assessed at End of Treatment by HCV Genotype and Presence of Insulin-Resistance at Baseline Other	1.3 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Timeframe: 24 weeks following completion of 24 or 48 weeks of therapy

Population: Completer set for the primary analysis (N=223) included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study. Of the 223 participants in this population, 29 participants demonstrated virological relapse (N=18 and N=11) and were therefore included in this analysis.

Virological relapse (VR) was assessed at the end of the study (Visit 4) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR >3) to investigate the percentage of participants who demonstrated VR. VR was defined as undetectable plasma HCV-RNA (RFT +) at end of treatment (Visit 3- considered Week 24 or Week 48 after treatment start depending on treatment duration), but lost RFT (considered sustained non-Responders) at end of study (Visit 4- considered Week 48 or Week 72 depending on a treatment duration of 24 or 48 weeks respectively).

Outcome measures

Measure	Pegylated Interferon and Ribavirin n=18 Participants Naïve patients with CHC of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.	HOMA-IR >3 n=11 Participants Subgroup of naïve patients with CHC of any genotype and a presence of insulin resistance at baseline treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.
Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype I	83.3 Percentage of Participants	72.7 Percentage of Participants
Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype II	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype III	16.7 Percentage of Participants	27.3 Percentage of Participants
Percentage of Participants Who Demonstrated Virological Relapse as Assessed at End of Study by HCV Genotype and Presence of Insulin-Resistance at Baseline Other	0 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Timeframe: Week 12 after treatment start

Population: Completer set for the primary analysis (N=223) included all participants who were administered at least one dose of the study treatment and provided the SVR data at end of study. Of the 223 participants in this population, 210 participants demonstrated early virological response (N=158 and N=50). 2 participants of the 210 had missing values.

Early Virological response (EVR) was assessed at 12 weeks after treatment start (Visit 2) by HCV genotype (I, II, III, or other) and presence of insulin-resistance at baseline (defined as HOMA-IR >3) to investigate the percentage of participants who achieved EVR. EVR was defined as a substantial (greater than 2 log10) decrease in viral load (measured as International Units/milliliter) and/or negative Polymerase chain reaction (PCR)-based viral load qualitative result as assessed at visit 2 of the study.

Outcome measures

Measure	Pegylated Interferon and Ribavirin n=158 Participants Naïve patients with CHC of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.	HOMA-IR >3 n=50 Participants Subgroup of naïve patients with CHC of any genotype and a presence of insulin resistance at baseline treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.
Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype I	51.3 Percentage of Participants	54.0 Percentage of Participants
Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype II	12.7 Percentage of Participants	6.0 Percentage of Participants
Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline Genotype III	34.8 Percentage of Participants	40.0 Percentage of Participants
Percentage of Participants Who Achieved Early Virological Response as Assessed at Visit 2 by HCV Genotype and Presence of Insulin-Resistance at Baseline Other	1.3 Percentage of Participants	0 Percentage of Participants

Adverse Events

Pegylated Interferon and Ribavirin

Serious events: 2 serious events

Other events: 177 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pegylated Interferon and Ribavirin n=250 participants at risk Naïve patients with chronic hepatitis C (CHC) of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.
Injury, poisoning and procedural complications Drug Exposure During Pregnancy	0.40% 1/250 • Number of events 1 Safety set: All participants who were administered at least one dose of the study treatment.
Nervous system disorders Acoustic Neuritis	0.40% 1/250 • Number of events 1 Safety set: All participants who were administered at least one dose of the study treatment.

Other adverse events

Measure	Pegylated Interferon and Ribavirin n=250 participants at risk Naïve patients with chronic hepatitis C (CHC) of any genotype treated with a standard treatment regimen of pegylated interferon and ribavirin according to routine clinical practice in Russia. Each dose of pegylated interferon was administered as a subcutaneous injection calculated as 1.5 mcg/kg once a week. The doses were corrected in case adverse events related to pegylated interferon registered. Ribavirin was taken orally as 200 mg gelatinous capsules. The daily dose varied from 800 to 1200 mg (depending on patient's body weight) twice daily in the morning and in the evening with meal. Therapy duration varied from 24 to 48 weeks depending on HCV genotype, viral load, activity and stage of hepatitis C.
Blood and lymphatic system disorders Anaemia	27.6% 69/250 • Number of events 69 Safety set: All participants who were administered at least one dose of the study treatment.
Blood and lymphatic system disorders Leukopenia	36.0% 90/250 • Number of events 90 Safety set: All participants who were administered at least one dose of the study treatment.
Blood and lymphatic system disorders Neutropenia	12.0% 30/250 • Number of events 30 Safety set: All participants who were administered at least one dose of the study treatment.
Blood and lymphatic system disorders Thrombocytopenia	20.0% 50/250 • Number of events 50 Safety set: All participants who were administered at least one dose of the study treatment.
General disorders Asthenia	12.4% 31/250 • Number of events 31 Safety set: All participants who were administered at least one dose of the study treatment.
General disorders Influenza Like Illness	36.4% 91/250 • Number of events 91 Safety set: All participants who were administered at least one dose of the study treatment.
General disorders Pyrexia	6.8% 17/250 • Number of events 17 Safety set: All participants who were administered at least one dose of the study treatment.
Investigations Weight Decreased	10.4% 26/250 • Number of events 26 Safety set: All participants who were administered at least one dose of the study treatment.
Psychiatric disorders Depression	10.0% 25/250 • Number of events 25 Safety set: All participants who were administered at least one dose of the study treatment.
Skin and subcutaneous tissue disorders Alopecia	5.6% 14/250 • Number of events 14 Safety set: All participants who were administered at least one dose of the study treatment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee PI agrees for a period of five years following the Effective Date to retain the Disclosure made to the SPONSOR or on behalf of SPONSOR, in confidence and not disclose it to any third party.
• Publication restrictions are in place

Restriction type: OTHER