Dutch Acute HCV in HIV Study (DAHHS)

• Sponsor: Erasmus Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01912495
• Collaborator: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other), Onze Lieve Vrouwe Gasthuis (Other), UMC Utrecht (Other), University Medical Center Groningen (Other), Maastricht University Medical Center (Other), Rijnstate Hospital (Other), Slotervaart Hospital (Other), Radboud University Medical Center (Other)
• Enrollment: 65
• Locations: 9
• Arm: 1
• Duration (Months): 29
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Prospective open label proof of concept feasibility interventional clinical trial in which 60 acute HCV genotype 1 patients co-infected with HIV will receive 12 weeks of boceprevir in addition to Standard Of Care Peginterferon + Ribavirin if they show a Rapid Viral Responds at week 4.

The primary hypothesis of this study is that the subset of patients with a Rapid Viral Responds after 4 weeks of triple therapy with boceprevir, peginterferon alpha-2b (P) and ribavirin (RVR4) can be successfully treated with a shorter 12-week triple therapy regimen.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C; Human Immunodeficiency Virus	Drug: Boceprevir	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy of 12 Week Boceprevir in Addition to Standard of Care Therapy Consisting of Peginterferon-alpha-2b and Ribavirin for the Treatment of Acute HCV Genotype 1 in HIV Co-infected Patients. A Proof of Concept Feasibility Clinical Trial.
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Boceprevir, peginterferon ribavirin All patients were intended to be treated in the 12 week peginterferon, ribavirin and boceprevir arm.	Drug: Boceprevir; Other Names: Victrelis

Outcome Measures

Primary Outcome Measures

1. Sustained Viral Response(SVR) 12 Weeks of Follow up After the End of All Therapy for the Rapid Viral Response at Week 4(RVR4) Population. [12 weeks]

   The outcome is a number of the patients with an undetectable Hepatitis C Virus (HCV) RNA at week 4 that have an undetectable HCV RNA 12 weeks after end of treatment.

Secondary Outcome Measures

1. SVR 12 Weeks After the End of All Therapy in the Entire Study Population (With or Without RVR4). [12 weeks]

   The outcome is a number of all patients who started treatment having an undetectable HCV RNA 12 weeks after the end of therapy

2. SVR 12 Weeks After End of Therapy in Patients With Already a RVR at Week 1. [12 weeks]

   The number of patients who were undetectable for HCV at week one that had an undetectable HCV RNA load 12 weeks after the end of treatment

3. SVR 12 Weeks After End of Therapy in Patients That Started Therapy ≤12weeks After the Presumed HCV Infection Date Versus Those After 12 Weeks. [12 weeks]

   The number of patients having a undetectable HCV RNA 12 weeks after the end of treatment in the group patients that was treated within 12 week of calculated transmission date.

4. Alterations of Biomarkers by Therapy Induced Viral Eradication: Viral Sequencing, Mutation Analysis, Gene Expression Analysis, and RNA Analysis. [72 weeks]

5. Safety: Treatment Related (Serious) Adverse Events ((S)AE) and Treatment Discontinuation for (S)AE. [72 weeks]

   only serious adverse events are recorded in this secondary endpoint

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Documented recent HCV genotype 1 infection (≤26 weeks old at the time of the baseline visit) according to definition mentioned below.

2. Plan to start a Standard Of Care therapy for acute HCV consisting of 24 weeks of Peginterferon + Ribavirin. HCV RNA plasma viral load at screening >1000 IU/ml.

3. A previously performed HCV RNA plasma measurement can be used for screening if <4 weeks old.

4. On HAART at the time of screening.

5. Minimum age 18 years.

Exclusion Criteria:

1. Disallowed co-medication that cannot be stopped or replaced: Several potentially life-threatening drug-drug interactions (DDI) are possible when boceprevir is combined with other drugs. Therefore ALL co-medication, including over-the-counter drugs should be checked for potential DDI with DDI table in the Dutch summary of product characteristics (SPC, appendix A). If the co-medication is not mentioned in the SPC DDI table, www.HCV-druginteractions.org should be used.

2. Contraindications for the use of full dose of peginterferon alpha-2b or ribavirin: neutrophils <0,75×109/l or thrombocytes < 100.000×109/l or a Hb <6.2mmol/L, creatinine clearance <50ml/min).

3. History of liver cirrhosis or >F1 fibrosis on fibroscan. Inclusion of patients with a chronic well-controlled HBV (HBV-DNA below the limit of detection) with tenofovir, lamivudine or emtricitabine therapy is allowed if fibroscan excludes >F1 fibrosis. Fibroscan reports <2 years old can be used for screening. Fibroscan is not required for other patients at screening.

4. HAART was started <4 weeks before baseline visit.

5. Inability to switch to a HAART regimen consisting of 2 nucleoside/tide reverse transcriptase inhibitors + Raltegravir (Isentress®) 400mg BID or rilpivirine 25mg QD or atazanavir (Reyataz®) 300mg QD + ritonavir (Norvir®) 100mg QD.

6. Patient that virologically failed HAART in the past

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Erasmus MC	Rotterdam	Zuid Holland	Netherlands	3000CA
2	AMC	Amsterdam		Netherlands
3	OLVG	Amsterdam		Netherlands
4	Slotervaart	Amsterdam		Netherlands
5	Ziekenhuis Rijnstate	Arnhem		Netherlands
6	UMCG	Groningen		Netherlands
7	MUMC	Maastricht		Netherlands
8	Radboud UMCN	Nijmegen		Netherlands
9	UMCU	Utrecht		Netherlands

Sponsors and Collaborators

• Erasmus Medical Center
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Onze Lieve Vrouwe Gasthuis
• UMC Utrecht
• University Medical Center Groningen
• Maastricht University Medical Center
• Rijnstate Hospital
• Slotervaart Hospital
• Radboud University Medical Center

Investigators

• Principal Investigator: Bart Rijnders, MD, PhD, Erasmus MC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bart Rijnders, MD,PhD, Erasmus Medical Center
• ClinicalTrials.gov Identifier: NCT01912495
• Other Study ID Numbers: NL44825.078.13
• First Posted: Jul 31, 2013
• Last Update Posted: Apr 1, 2016
• Last Verified: Mar 1, 2016

• Additional relevant MeSH terms: Hepatitis C; Acquired Immunodeficiency Syndrome; HIV Infections

Study Results

Participant Flow

Arm/Group Title	Boceprevir
Arm/Group Description	12 week Boceprevir, Peginterferon and Ribavirin in RVR4 group
Period Title: Overall Study
STARTED	57
COMPLETED	57
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Boceprevir/Peginterferon/Ribavirin
Arm/Group Description	Boceprevir with Peginterferon and Ribavirin
Overall Participants	57
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	40
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	57 100%
Region of Enrollment (participants) [Number]
Netherlands	57 100%

Outcome Measures

1. Primary Outcome

Title	Sustained Viral Response(SVR) 12 Weeks of Follow up After the End of All Therapy for the Rapid Viral Response at Week 4(RVR4) Population.
Description	The outcome is a number of the patients with an undetectable Hepatitis C Virus (HCV) RNA at week 4 that have an undetectable HCV RNA 12 weeks after end of treatment.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

41 patients had a RVR4

Arm/Group Title	Boceprevir, Peginterferon and Ribavirin
Arm/Group Description	12 week Boceprevir, Peginterferon and Ribavirin
Measure Participants	41
Number [participants]	41 71.9%

2. Secondary Outcome

Title	SVR 12 Weeks After the End of All Therapy in the Entire Study Population (With or Without RVR4).
Description	The outcome is a number of all patients who started treatment having an undetectable HCV RNA 12 weeks after the end of therapy
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Total intention to treat population

Arm/Group Title	Boceprevir, Peginterferon and Ribavirin
Arm/Group Description	12 week boceprevir, peginterferon and ribavirin in intention to treat group
Measure Participants	57
Number [participants]	49 86%

3. Secondary Outcome

Title	SVR 12 Weeks After End of Therapy in Patients With Already a RVR at Week 1.
Description	The number of patients who were undetectable for HCV at week one that had an undetectable HCV RNA load 12 weeks after the end of treatment
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All patients having a rapid viral response at week 4 had a sustained viral response at 12(SVR12) weeks after treatment.

Arm/Group Title	Boceprevir, Peginterferon and Ribavirin
Arm/Group Description	12 week Boceprevir, Peginterferon and Ribavirin
Measure Participants	5
Number [participants]	5 8.8%

4. Secondary Outcome

Title	SVR 12 Weeks After End of Therapy in Patients That Started Therapy ≤12weeks After the Presumed HCV Infection Date Versus Those After 12 Weeks.
Description	The number of patients having a undetectable HCV RNA 12 weeks after the end of treatment in the group patients that was treated within 12 week of calculated transmission date.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

5 patients were treated within 12 weeks after calculated transmission date. All other patients were treated between 12 and 26 weeks after calculated transmission date.

Arm/Group Title	Boceprevir Peginterferon Ribavirin
Arm/Group Description	12 week Boceprevir peginterferon and ribavirin
Measure Participants	5
Number [participants]	5 8.8%

5. Secondary Outcome

Title	Alterations of Biomarkers by Therapy Induced Viral Eradication: Viral Sequencing, Mutation Analysis, Gene Expression Analysis, and RNA Analysis.
Time Frame	72 weeks

Outcome Measure Data

Analysis Population Description

data were not collected during this study

Arm/Group Title	Boceprevir Peginterferon Ribavirin
Arm/Group Description	Boceprevir peginterferon and ribavirin
Measure Participants	0

6. Secondary Outcome

Title	Safety: Treatment Related (Serious) Adverse Events ((S)AE) and Treatment Discontinuation for (S)AE.
Description	only serious adverse events are recorded in this secondary endpoint
Time Frame	72 weeks

Outcome Measure Data

Analysis Population Description

57 patients started treatment and were at risk

Arm/Group Title	Boceprevir, Peginterferon and Ribavirin
Arm/Group Description	12 week boceprevir, peginterferon and ribavirin in intention to treat group
Measure Participants	57
Number [participants]	3 5.3%

Adverse Events

Arm/Group Title	Boceprevir
Arm/Group Description	12 week Boceprevir, Peginterferon and Ribavirin in RVR4 group
All Cause Mortality
	Boceprevir
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Boceprevir
	Affected / at Risk (%)	# Events
Total	3/57 (5.3%)
Cardiac disorders
Myocardial infarction	1/57 (1.8%)
General disorders
anemia	1/57 (1.8%)
Vascular disorders
transient ischemic attack	1/57 (1.8%)
Other (Not Including Serious) Adverse Events
	Boceprevir
	Affected / at Risk (%)	# Events
Total	54/57 (94.7%)
Blood and lymphatic system disorders
Anemia	47/57 (82.5%)
anemia	7/57 (12.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.