The TAP Study: Treating People Who Inject Drugs in Community-Based Settings Using a Social Network Approach

Macfarlane Burnet Institute for Medical Research and Public Health Ltd

Status and phase: Unknown; Phase 3

Conditions: Hepatitis C; Drug Abuse, Intravenous

Treatments: Drug: Sofosbuvir/ledispasvir fixed dose combination (SOF + LDP)

Study type: Interventional

Funder types: Other

Identifiers

NCT02363517

MacfarlaneBIMRPH

Details and patient eligibility

About

This study will investigate the feasibility of treating people who inject drugs (PWID) with hepatitis C virus (HCV) in community-based settings with a 12-week course of oral therapy combination of sofosbuvir plus ledipasvir. It will also measure the effectiveness of using a social network-based approach to reduce HCV incidence among PWID.

Full description

This study will investigate the feasibility of treating people who inject drugs (PWID) with hepatitis C virus (HCV) in community-based settings with a 12-week course of oral therapy combination of sofosbuvir plus ledipasvir (SOF + LDP). It will also measure the effectiveness of using a social network-based approach ("bring your friends") to reduce HCV incidence among PWID. Participants will initially be sourced from the Burnet Institute's existing SuperMIX cohort (N= 757). This cohort comprises PWID followed for between two and six years (median=1057 days), of whom 299 have chronic HCV infection. The HCV genotype distribution in the SuperMIX cohort is: HCV-1 (55%); HCV-3 (40%) and HCV-6 (<5%).

Participants will be randomly allocated to three groups:

Group 1: Primary (n=40) and secondary (n=100) participants will receive supportive care only.

Group 2: Primary participants (n=40) will be treated with SOF + LDP for 12 weeks. Secondary participants (n=100) will receive supportive care only.

Group 3: Primary (n=40) and secondary participants with chronic HCV infection (n=50%*100) will be treated with SOF + LDP for 12 weeks. Participants in Group C who have evidence of HCV re-infection will be offered re-treatment with SOF + LDP for 12 weeks.

Treatment participants will have a clinical review, questionnaire and blood sample collected at baseline, weeks 4, 8 and 12 (end-of-treatment), and at weeks 12 (SVR12), 24 (SVR24), 36, 48, 60 and 72 post-treatment. Non-treatment participants will have a clinical review, questionnaire and blood sample collected at baseline and weeks 12, 24, 36, 48, 60, 72 and 84.

Enrollment: 420 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

SECONDARY PARTICIPANTS INCLUSION AND EXCLUSION CRITERIA

Study INCLUSION criteria for primary participants are as follows:

• Current PWID (i.e., injected any drug at least once during the previous six months);
• Evidence of chronic HCV infection (detectable plasma HCV RNA viral load above 1000 IU/ml on two occasions ≥ 6 months apart)
• Willing and able to provide written informed consent.

Subjects must have the following laboratory parameters at screening:

• ALT <10 times the upper limit of normal (ULN)
• AST <10 times ULN
• Haemoglobin ≥12g/dL for males, ≥11g/dL for female subjects
• INR ≤1.5 times ULN unless is stable on an anticoagulant regimen affecting INR
• Albumin ≥3g/dL
• Direct bilirubin ≤1.5 times ULN
• Creatinine clearance (CLcr) ≥60mL/min, as calculated by the Cockcroft-Gault Equation.

EXCLUSION criteria for all primary participants are as follows:

• Testing positive for HIV
• History of, or current, decompensated liver disease
• Testing positive for HBsAg
• HCC
• Women who are pregnant or breastfeeding, or men with female partners who are pregnant at screening or baseline, or who were pregnant in the six months prior to screening
• Already enrolled in the TAP Study as a secondary participant (see below)
• Evidence of any condition, therapy, laboratory abnormality or other circumstance (current or prior) that may confound the study's results, or interfere with participation for the full duration of the study, such that it is not in the best interest of the participant;
• Use of concomitant medications.

Additional EXCLUSION criteria for primary participants with HCV genotypes 2-6:

• Increased baseline risk for anaemia (e.g., a history of thalassemia, spherocytosis, history of GI bleeding), or for whom anaemia would be medically problematic;
• Documented or presumed coronary artery disease or cerebrovascular disease if, in the judgment of the investigator, an acute decrease in haemoglobin by up to 4g/dL (as may be seen with ribavirin therapy) would not be well-tolerated.

SECONDARY PARTICIPANTS INCLUSION AND EXCLUSION CRITERIA

The INCLUSION criteria for secondary participants are as follows:

• Is nominated by a primary participant as a current injecting partner (i.e., has engaged in IDU with a primary participant in the previous six months)
• Willing and able to provide written informed consent.

There are no exclusion criteria for secondary participants who are not receiving HCV therapy in this protocol:

EXCLUSION criteria for treated secondary participants (i.e., those in Group C who are HCV positive) are as follows:

• History of, or current, decompensated liver disease
• Women who are pregnant or breastfeeding, or men with female partners who are pregnant at screening or baseline, or who were pregnant in the six months prior to screening
• Testing positive for HIV
• Testing positive for HBsAg
• HCC
• Evidence of any condition, therapy, laboratory abnormality or other circumstance (current or prior) that may confound the study's results, or interfere with participation for the full duration of the study, such that it is not in the best interest of the participant
• Use of concomitant medications.

Additional EXCLUSION criteria for secondary participants with HCV genotypes 2-6:

• Increased baseline risk for anaemia (e.g. a history of thalassemia, spherocytosis, history of GI bleeding) or for whom anaemia would be medically problematic
• Documented or presumed coronary artery disease or cerebrovascular disease if, in the judgment of the investigator, an acute decrease in haemoglobin by up to 4g/dL (as may be seen with ribavirin therapy) would not be well-tolerated.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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420 participants in 3 patient groups

Group A

No Intervention group

Description:

Primary (n=40) and secondary (n=100) participants will receive supportive care only (includes a clinical review, questionnaire and blood sample collected at baseline and weeks 12, 24, 36, 48, 60, 72 and 84). Participants with HCV not allocated to treatment arms will receive deferred treatment at the end of the follow-up period.

Group B

Active Comparator group

Description:

Primary participants (n=40) will be treated with 'Sofosbuvir/ledispasvir fixed dose combination (SOF + LDP) for 12 weeks. Secondary participants (n=100) will receive supportive care only. Participants with HCV not allocated to treatment arms will receive deferred treatment at the end of the follow-up period.

Treatment:

Drug: Sofosbuvir/ledispasvir fixed dose combination (SOF + LDP)

Group C

Active Comparator group

Description:

Primary (n=40) and secondary participants with chronic HCV infection (approx. n=50%\*100) will be treated with 'Sofosbuvir/ledispasvir fixed dose combination (SOF + LDP) for 12 weeks. Participants in Group C who have evidence of HCV re-infection will be offered re-treatment with SOF + LDP for 12 weeks.

Treatment:

Drug: Sofosbuvir/ledispasvir fixed dose combination (SOF + LDP)