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Clinical Trial Results:
Pilot study to assess efficacy and safety of Sofosbuvir/Ledipasvir (GS-5885) fixed-dose combination in NS3/4A protease inhibitor-experienced subjects with HCV genotype 1 infection and HIV co-infection

Summary
EudraCT number	2013-002607-33
Trial protocol	FR
Global end of trial date	04 Dec 2015

Results information
Results version number	v1(current)
This version publication date	08 Mar 2024
First version publication date	08 Mar 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

ANRS HC 31 SOFTRIH

ISRCTN number

US NCT number

NCT02125500

WHO universal trial number (UTN)

Sponsor organisation name

Inserm-ANRS

Sponsor organisation address

101 rue de Tolbiac, Paris, France, 75013

Public contact

Pr. Eric Rosenthal, Service de Médecine interne, +33 4 92 03 58 51, rosenthal.e@chu-nice.fr

Scientific contact

Pr. Eric Rosenthal, Service de Médecine interne, +33 4 92 03 58 51, rosenthal.e@chu-nice.fr

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

11 Mar 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

04 Dec 2015

Was the trial ended prematurely?

Main objective of the trial

To assess, in patients with HCV genotype 1 infection and HIV co-infection, who had previously failed a NS3/4A protease inhibitor plus PEG/RBV regiment or stopped prematurely their treatment for intolerance, the rate of sustained virological response (SVR) 12 weeks after 24 weeks of treatment in cirrhotic patients and 12 weeks in non-cirrhotic patients with oral Sofosbuvir/Ledipasvir fixed-dose combination, and to determine whether this SVR rate is significantly above 50%.

Protection of trial subjects

This study was conducted in accordance with the updated Declaration of Helsinki, in compliance with the approved protocol and its amendments, the International Council for Harmonisation guideline for Good Clinical Practice (ICH GCP), and French regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Aug 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 68

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Patients were recruited from 30 clinical centers in France from August 2014 to March 2015.

Screening details

Main criteria: Inclusion: at least 18 years old, confirmed HIV infection, infection with HCV genotype 1 only (confirmed at screen visit) Non-inclusion: Child-Pugh B or C cirrhosis or history of decompensated cirrhosis, co-infection with Hepatitis B virus (AgHBs)

Period 1 title

Overall period

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Global

Arm description

Arm type

Experimental

Investigational medicinal product name

Sofosbuvir/Ledipasvir

Investigational medicinal product code

Other name

SOF/LDV

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

SOF: 400 mg LDV: 90 mg The tablet is administered orally, once daily, without regard to food. It is recommended to take their dose in the morning. To be taken during 12 weeks for non-cirrhotic patients and during 24 weeks for cirrhotic patients.

Investigational medicinal product name

Stable antiretroviral combination

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

The patients enrolled in the study had to receive a stable antiretroviral combination of emtricitabine/tenofovir (TRUVADA®) or lamivudine/tenofovir (EPIVIR® + VIREAD®) standard of care backbone plus efavirenz (SUSTIVA®) or raltegravir (ISENTRESS®) or rilpivirine (EDURANT®) or enfuvirtide (FUZEON®). Alternative combinations of the above listed medications were allowed. Single tablets regimen containing emtricitabine/tenofovir plus efavirenz or rilpivirine (ATRIPLA® or EVIPLERA®) were permitted. To be taken during 12 weeks for non-cirrhotic patients and during 24 weeks for cirrhotic patients.

Number of subjects in period 1	Global
Started	68
Completed	65
Not completed	3
Protocol deviation	3

Baseline characteristics

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Reporting group title

Global

Reporting group description

Reporting group values	Global	Total
Number of subjects	68	68
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	64	64
From 65-84 years	4	4
85 years and over	0	0
Age continuous
Units: years
median (inter-quartile range (Q1-Q3))	52 (49 to 54)	-
Gender categorical
Units: Subjects
Female	14	14
Male	54	54

Subject analysis set title

Cirrhotic

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subset formed by the cirrhotic patients.

Subject analysis set title

Non-cirrhotic

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subset formed by non-cirrhotic patients

Subject analysis sets values	Cirrhotic	Non-cirrhotic
Number of subjects	27	41
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	26	38
From 65-84 years	1	3
85 years and over	0	0
Age continuous
Units: years
median (inter-quartile range (Q1-Q3))	53 (51 to 55)	52 (48 to 54)
Gender categorical
Units: Subjects
Female	8	6
Male	19	35

End points

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Reporting group title

Global

Reporting group description

Subject analysis set title

Cirrhotic

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subset formed by the cirrhotic patients.

Subject analysis set title

Non-cirrhotic

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subset formed by non-cirrhotic patients

Primary: SVR12

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End point title

SVR12 ^[1]

End point description

The primary endpoint is the sustained virological response, defined by an undetectable HCV RNA 12 weeks post-treatment (SVR12)

End point type

Primary

End point timeframe

Analyses made 12 weeks after treatment stop. W36 for cirrhotic patients and W24 for non-cirrhotic patients.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint concerns a single arm, adding statistical analyses create errors. See attachments for data.

End point values	Global	Cirrhotic	Non-cirrhotic
Number of subjects analysed	68	27	41
Units: Number of patients	65	25	40

Attachments

SOFTRIH Endpoint data

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Participants reported adverse events during the entire time of the trial.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Non-cirrhotic

Reporting group description

Reporting group title

Cirrhotic

Reporting group description

Reporting group title

Global

Reporting group description

Serious adverse events	Non-cirrhotic	Cirrhotic	Global
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 41 (7.32%)	8 / 27 (29.63%)	11 / 68 (16.18%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 41 (2.44%)	1 / 27 (3.70%)	2 / 68 (2.94%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gamma-glutamyltransferase increased
subjects affected / exposed	2 / 41 (4.88%)	1 / 27 (3.70%)	3 / 68 (4.41%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Wrist fracture
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Arteritis
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Craniocerebral injury
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
General physical health deterioration
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malaise
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastric ulcer
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Lung disorder
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 41 (0.00%)	1 / 27 (3.70%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Non-cirrhotic	Cirrhotic	Global
Total subjects affected by non serious adverse events
subjects affected / exposed	41 / 41 (100.00%)	27 / 27 (100.00%)	68 / 68 (100.00%)
Vascular disorders
Hypertension
subjects affected / exposed	10 / 41 (24.39%)	4 / 27 (14.81%)	14 / 68 (20.59%)
occurrences all number	10	4	14
General disorders and administration site conditions
Asthenia
subjects affected / exposed	6 / 41 (14.63%)	11 / 27 (40.74%)	17 / 68 (25.00%)
occurrences all number	6	11	17
Influenza like illness
subjects affected / exposed	3 / 41 (7.32%)	1 / 27 (3.70%)	4 / 68 (5.88%)
occurrences all number	4	1	5
Psychiatric disorders
Anxiety
subjects affected / exposed	2 / 41 (4.88%)	2 / 27 (7.41%)	4 / 68 (5.88%)
occurrences all number	2	2	4
Depression
subjects affected / exposed	3 / 41 (7.32%)	2 / 27 (7.41%)	5 / 68 (7.35%)
occurrences all number	3	2	5
Insomnia
subjects affected / exposed	3 / 41 (7.32%)	3 / 27 (11.11%)	6 / 68 (8.82%)
occurrences all number	3	3	6
Investigations
Alanine aminotransferase increased
subjects affected / exposed	6 / 41 (14.63%)	5 / 27 (18.52%)	11 / 68 (16.18%)
occurrences all number	8	6	14
Aspartate aminotransferase increased
subjects affected / exposed	8 / 41 (19.51%)	9 / 27 (33.33%)	17 / 68 (25.00%)
occurrences all number	13	10	23
Gamma-glutamyltransferase increased
subjects affected / exposed	5 / 41 (12.20%)	7 / 27 (25.93%)	12 / 68 (17.65%)
occurrences all number	5	8	13
Blood HIV RNA increased
subjects affected / exposed	2 / 41 (4.88%)	2 / 27 (7.41%)	4 / 68 (5.88%)
occurrences all number	3	2	5
Blood bicarbonate decreased
subjects affected / exposed	8 / 41 (19.51%)	12 / 27 (44.44%)	20 / 68 (29.41%)
occurrences all number	11	19	30
Blood phosphorus decreased
subjects affected / exposed	6 / 41 (14.63%)	5 / 27 (18.52%)	11 / 68 (16.18%)
occurrences all number	11	11	22
Nervous system disorders
Headache
subjects affected / exposed	4 / 41 (9.76%)	4 / 27 (14.81%)	8 / 68 (11.76%)
occurrences all number	4	5	9
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	2 / 41 (4.88%)	10 / 27 (37.04%)	12 / 68 (17.65%)
occurrences all number	6	18	24
Leukopenia
subjects affected / exposed	4 / 41 (9.76%)	5 / 27 (18.52%)	9 / 68 (13.24%)
occurrences all number	6	13	19
Neutropenia
subjects affected / exposed	2 / 41 (4.88%)	4 / 27 (14.81%)	6 / 68 (8.82%)
occurrences all number	3	8	11
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	1 / 41 (2.44%)	3 / 27 (11.11%)	4 / 68 (5.88%)
occurrences all number	1	3	4
Nausea
subjects affected / exposed	4 / 41 (9.76%)	2 / 27 (7.41%)	6 / 68 (8.82%)
occurrences all number	4	2	6
Hepatobiliary disorders
Hyperbilirubinaemia
subjects affected / exposed	3 / 41 (7.32%)	4 / 27 (14.81%)	7 / 68 (10.29%)
occurrences all number	3	5	8
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	2 / 41 (4.88%)	2 / 27 (7.41%)	4 / 68 (5.88%)
occurrences all number	2	4	6
Renal and urinary disorders
Proteinuria
subjects affected / exposed	24 / 41 (58.54%)	13 / 27 (48.15%)	37 / 68 (54.41%)
occurrences all number	46	22	68
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 41 (4.88%)	2 / 27 (7.41%)	4 / 68 (5.88%)
occurrences all number	2	3	5
Back pain
subjects affected / exposed	1 / 41 (2.44%)	4 / 27 (14.81%)	5 / 68 (7.35%)
occurrences all number	2	4	6
Infections and infestations
Bronchitis
subjects affected / exposed	2 / 41 (4.88%)	3 / 27 (11.11%)	5 / 68 (7.35%)
occurrences all number	3	4	7
Nasopharyngitis
subjects affected / exposed	4 / 41 (9.76%)	1 / 27 (3.70%)	5 / 68 (7.35%)
occurrences all number	4	1	5
Metabolism and nutrition disorders
Hypophosphataemia
subjects affected / exposed	15 / 41 (36.59%)	8 / 27 (29.63%)	23 / 68 (33.82%)
occurrences all number	25	12	37
Hypokalaemia
subjects affected / exposed	6 / 41 (14.63%)	3 / 27 (11.11%)	9 / 68 (13.24%)
occurrences all number	7	11	18
Hyponatraemia
subjects affected / exposed	3 / 41 (7.32%)	3 / 27 (11.11%)	6 / 68 (8.82%)
occurrences all number	4	3	7
Hypercholesterolaemia
subjects affected / exposed	5 / 41 (12.20%)	1 / 27 (3.70%)	6 / 68 (8.82%)
occurrences all number	5	1	6
Hypercreatininaemia
subjects affected / exposed	9 / 41 (21.95%)	8 / 27 (29.63%)	17 / 68 (25.00%)
occurrences all number	17	16	33
Hyperuricaemia
subjects affected / exposed	3 / 41 (7.32%)	2 / 27 (7.41%)	5 / 68 (7.35%)
occurrences all number	4	3	7

More information

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Were there any global substantial amendments to the protocol? Yes

12 Mar 2014

The substantial modifications included in the amendment 1 of the protocol are: - review and modification of the criterion for discontinuation of treatment in case of virological rebound - rewording of the non-inclusion criterion concerning contraindications to the experimental treatment in order to be consistent with the "Contra-indicated treatments" part of the protocol.

09 Jul 2014

The substantial modifications included in the amendement 2 of the protocol are: - modification of the trial's therapeutic strategy - clarification of the criterion for stopping HCV treatment for virological reasons - update of the list of prohibited treatments.

10 Dec 2014

The substantial modifications included in the amendment 3 of the protocol are: - clarification of the conditions for changing antiretroviral treatment after stopping experimental anti-HCV treatment - modification of the list of contra-indicated antiviral treatments.

11 Feb 2015

The substantial modifications included in the amendment 4 of the protocol are: - modification of the criteria for determining the fibrosis score - deletion of a virological criterion for discontinuation of HCV treatment - update of safety data - modification of the interaction data, the list of contra-indicated treatments and treatments to be used with caution - modification of the adverse event severity rating scale used for the "bicarbonate" item.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/29214737

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Clinical trials

Clinical Trial Results:
Pilot study to assess efficacy and safety of Sofosbuvir/Ledipasvir (GS-5885) fixed-dose combination in NS3/4A protease inhibitor-experienced subjects with HCV genotype 1 infection and HIV co-infection

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: SVR12

Primary: SVR12

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

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Clinical trials

Clinical Trial Results: Pilot study to assess efficacy and safety of Sofosbuvir/Ledipasvir (GS-5885) fixed-dose combination in NS3/4A protease inhibitor-experienced subjects with HCV genotype 1 infection and HIV co-infection

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: SVR12

Primary: SVR12

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
Pilot study to assess efficacy and safety of Sofosbuvir/Ledipasvir (GS-5885) fixed-dose combination in NS3/4A protease inhibitor-experienced subjects with HCV genotype 1 infection and HIV co-infection