Comparison of Sofosbuvir/Velpatasvir Fixed Dose Combinati... | NCT02201953

ID	Type	Description	Link
2014-001682-27	EudraCT Number

Label	Type	Description	Intervention Names
SOF/VEL 12 Weeks	Experimental	SOF/VEL FDC for 12 weeks	Drug: SOF/VEL
SOF+RBV 24 Weeks	Experimental	SOF+RBV for 24 weeks	Drug: SOF Drug: RBV

Name	Type	Description	Arm Group Labels	Other Names
SOF/VEL	Drug	400/100 mg FDC tablet administered orally once daily	SOF/VEL 12 Weeks

Measure	Description	Time Frame
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event		Up to 24 weeks

Measure	Description	Time Frame
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR4 and SVR24 are defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug.	Posttreatment Weeks 4 and 24
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Willing and able to provide written informed consent
HCV RNA ≥ 10^4 IU/mL
HCV genotype 3
Chronic HCV infection (≥ 6 months)
Females of childbearing potential must have a negative serum pregnancy test
Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

Exclusion Criteria:

Current or prior history of clinically-significant illness (other than HCV) that may interfere with subject treatment, assessment or compliance with the protocol
Screening ECG with clinically significant abnormalities
Laboratory results outside of acceptable ranges at Screening
Pregnant or nursing female or male with pregnant female partner
Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, cholangitis)
Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)

Name	Affiliation	Role
John McNally, PhD	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Los Angeles	California	90027	United States

References Module

Citations

PubMed Identifier	Type	Citation
	Result	Asselah T, Charlton M, Feld J, Foster GR, Mcnally J, Brainard DM, et al. The ASTRAL Studies: Evaluation of SOF/GS-5816 Single Tablet Regimen for the Treatment of Genotype 1-6 HCV Infection [Poster P1332]. J Hepatol 2015;62:S855-S6.
	Result	Mangia, A., Roberts, SK., Pianko, S., Thompson, A at al. Sofosbuvir/GS-5816 Fixed Dose Combination for 12 Weeks Compared to Sofosbuvir with Ribavirin for 24 Weeks in Genotype 3 HCV Infected Patients: The Randomized Controlled Phase 3 ASTRAL-3 Study. Hepatology 2015; 62: 1 (SUPPL) 338A.
26575258	Result	Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17.

ID	Title	Description
FG000	SOF/VEL 12 Weeks	Sofosbuvir/velpatasvir (SOF/VEL) (400/100 mg) fixed-dose combination (FDC) tablet administered orally once daily for 12 weeks
FG001	SOF+RBV 24 Weeks	Sofosbuvir (SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) administered orally for 24 weeks

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00049± 10.4 BG00150± 10.0 BG00250± 10.2

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000107 BG001101 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00011 BG00111 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Black or African American

Title	Measurements
	BG0003 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

New Zealand

Title	Measurements
	BG0009 BG0018 BG002

HCV Genotype

Number

participants

Title

Denominators

Categories

Genotype 3 (No Confirmed Subtype)

Title	Measurements
	BG0009 BG00118 BG002

Cirrhosis Status

Number

participants

Title

Denominators

Categories

Yes

Title	Measurements
	BG00080 BG00183 BG002

IL28b Status

The CC, CT, and TT alleles are different forms of the IL28b gene.

Number

participants

Title

Denominators

Categories

Title	Measurements
	BG000105 BG001111 BG002

HCV RNA

Mean

Standard Deviation

log10 IU/mL

Title

Denominators

Categories

Title	Measurements
	BG0006.2± 0.72 BG0016.3± 0.71 BG002

HCV RNA Category

Number

participants

Title

Denominators

Categories

< 800,000 IU/mL

Title	Measurements
	BG00086 BG00181 BG002

Prior HCV Treatment Experience

Number

participants

Title

Denominators

Categories

Treatment-Naive

Title	Measurements
	BG000206 BG001204 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)

SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

Posttreatment Week 12

ID	Title	Description
OG000	SOF/VEL 12 Weeks	SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
OG001	SOF+RBV 24 Weeks	SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) administered orally for 24 weeks

Units	Counts
Participants	OG000277 OG001275

Title

Denominators

Categories

Title	Measurements
	OG00095.3(92.1 to 97.5) OG00180.7(75.6 to 85.2)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Difference in proportions	14.4			2-Sided	95	9.2	19.6			Difference in proportions between treatment groups and associated 95% confidence intervals (CI) are calculated based on stratum-adjusted Mantel-Haenszel proportions.		Non-Inferiority or Equivalence	Primary analyses consisted of non-inferiority test of Group 1 (SOF/VEL 12 weeks) versus Group 2 (SOF+RBV 24 weeks) at the 0.05 significance level. Non-inferiority was assessed using the conventional confidence interval approach and a non-inferiority margin of 10% was applied. The two-sided 95% confidence intervals was constructed using stratum-adjusted Mantel-Haenszel proportions, stratified by the randomization stratification factors (i.e cirrhosis status and prior treatment experience)

Primary

Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event

Safety Analysis Set

Posted

Number

percentage of participants

Up to 24 weeks

ID	Title	Description
OG000	SOF/VEL 12 Weeks	SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
OG001	SOF+RBV 24 Weeks	SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) administered orally for 24 weeks

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)

SVR4 and SVR24 are defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug.

Full Analysis Set

Posted

Number

95% Confidence Interval

percentage of participants

Posttreatment Weeks 4 and 24

ID	Title	Description
OG000	SOF/VEL 12 Weeks	SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
OG001	SOF+RBV 24 Weeks	SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) administered orally for 24 weeks

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

Participants in the Full Analysis Set with available data were analyzed.

Posted

Number

95% Confidence Interval

percentage of participants

Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

ID	Title	Description
OG000	SOF/VEL 12 Weeks	SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
OG001	SOF+RBV 24 Weeks	SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) administered orally for 24 weeks

Units	Counts
Participants	OG000

Secondary

Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

Participants in the Full Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

log10 IU/mL

Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

ID	Title	Description
OG000	SOF/VEL 12 Weeks	SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
OG001	SOF+RBV 24 Weeks	SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) administered orally for 24 weeks

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Virologic Failure

Virologic failure was defined as:

On-treatment virologic failure:
- Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
- Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
- Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
Virologic relapse:
- Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

Full Analysis Set

Posted

Number

percentage of participants

Up to Posttreatment Week 24

ID	Title	Description
OG000	SOF/VEL 12 Weeks	SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
OG001	SOF+RBV 24 Weeks	SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) administered orally for 24 weeks

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected277 at risk EG0010 affected275 at risk
Food poisoning	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected277 at risk EG0010 affected275 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected277 at risk EG0010 affected275 at risk
Death	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected277 at risk EG0010 affected275 at risk
Cellulitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Lung infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Propionibacterium infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Forearm fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Gun shot wound	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Intracranial aneurysm	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected277 at risk EG0010 affected275 at risk
Ruptured cerebral aneurysm	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Depression	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Psychotic disorder	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Ovarian cyst ruptured	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected277 at risk EG0010 affected275 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk
Peripheral artery stenosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected277 at risk EG0011 affected275 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected277 at risk EG00125 affected275 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected277 at risk EG00119 affected275 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00013 affected277 at risk EG00121 affected275 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00020 affected277 at risk EG00121 affected275 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected277 at risk EG00130 affected275 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00047 affected277 at risk EG00158 affected275 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected277 at risk EG00120 affected275 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG00016 affected277 at risk EG00126 affected275 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG00071 affected277 at risk EG001105 affected275 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected277 at risk EG00114 affected275 at risk
Bronchitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0006 affected277 at risk EG00114 affected275 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00034 affected277 at risk EG00133 affected275 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected277 at risk EG00114 affected275 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected277 at risk EG00122 affected275 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00025 affected277 at risk EG00120 affected275 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00013 affected277 at risk EG00117 affected275 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected277 at risk EG00115 affected275 at risk
Disturbance in attention	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected277 at risk EG00114 affected275 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG00015 affected277 at risk EG00121 affected275 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG00090 affected277 at risk EG00190 affected275 at risk
Anxiety	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected277 at risk EG00121 affected275 at risk
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG00032 affected277 at risk EG00174 affected275 at risk
Irritability	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG00023 affected277 at risk EG00140 affected275 at risk
Sleep disorder	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected277 at risk EG00115 affected275 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00014 affected277 at risk EG00135 affected275 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected277 at risk EG00122 affected275 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected277 at risk EG00120 affected275 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected277 at risk EG00125 affected275 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected277 at risk EG00135 affected275 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00015 affected277 at risk EG00114 affected275 at risk

ID	Term
D006526	Hepatitis C
D005355	Fibrosis

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D006525	Hepatitis, Viral, Human
D014777	Virus Diseases
D018178	Flaviviridae Infections
D012327	RNA Virus Infections
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D014542	Uridine Monophosphate
D014500	Uracil Nucleotides
D011742	Pyrimidine Nucleotides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D009711	Nucleotides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D012265	Ribonucleotides

ID	Title	Description
BG000	SOF/VEL 12 Weeks	SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
BG001	SOF+RBV 24 Weeks	SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) administered orally for 24 weeks
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	SOF/VEL 12 Weeks	SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks			6	277	216	277
EG001	SOF+RBV 24 Weeks	SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 24 weeks			15	275	243	275

ID	Term
C000611331	sofosbuvir-velpatasvir drug combination
D000069474	Sofosbuvir