Efficacy and Safety of MP-424, Peginterferon Alfa-2a (PEG-IFN Alfa-2a), and Ribavirin(RBV) in Treatment-Naïve or Relapsed Hepatitis C

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01753557
• Collaborator: (none)
• Enrollment: 54
• Location: 1
• Arms: 2
• Duration (Months): 23
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of MP-424 with PEG-IFN Alfa-2a and RBV in patients with genotype 1 hepatitis C, who are naïve to its treatment or relapsed after previous treatment.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C (CHC)	Drug: MP-424; Drug: RBV; Drug: PEG-IFN alfa-2a	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study of MP-424 in Combination With PEG-IFN Alfa-2a and RBV, in Subjects With Genotype 1 Hepatitis C, Who Are Treatment-Naïve or Relapsed After Previous Treatment
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment-Naive	Drug: MP-424; MP-424: 750mg every 8 hours (q8h) for 12 weeks; Drug: RBV; RBV: 600 - 1000 mg/day based on body weight for 24 weeks; Drug: PEG-IFN alfa-2a; PEG-IFN alfa-2a: 180mcg/week for 24 weeks
Experimental: Treatment-Relapsed	Drug: MP-424; MP-424: 750mg every 8 hours (q8h) for 12 weeks; Drug: RBV; RBV: 600 - 1000 mg/day based on body weight for 24 weeks; Drug: PEG-IFN alfa-2a; PEG-IFN alfa-2a: 180mcg/week for 24 weeks

Outcome Measures

Primary Outcome Measures

1. Undetectable HCV (Hepatitis C Virus) RNA (Ribonucleic Acid) at 24 Weeks After Completion of Drug Administration (SVR, Sustained Viral Response) [48 weeks]

Secondary Outcome Measures

1. Undetectable HCV RNA at 4 Weeks After Beginning of Drug Administration (RVR, Rapid Viral Response) [4 weeks]

2. Undetectable HCV RNA at Completion of Drug Administration (ETR, End-of-treatment Response) [24 weeks]

3. Undetectable HCV RNA at 12 Weeks After Completion of Drug Administration [36 weeks]

4. Transition of Serum HCV RNA Levels [baseline，Day2，Day3，1Weeks，2Weeks，3Weeks，4Weeks，End of treatment，Follow-up 12weeks，Follow-up 24weeks]

5. Viral Sequencing at the Non-structural 3 Protease Region of HCV Virus（Result of Resistance-associated Variants Analysis) [From baseline to 24 weeks after completion of drug administration]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Genotype 1 CHC

• treatment-naïve or relapsers (patient who relapsed after previous treatment)

• Able and willing to follow contraception requirements

Exclusion Criteria:

• Cirrhosis of the liver or hepatic failure

• Hepatitis B surface antigen-positive or HIV (Human Immunodeficiency Virus) antibodies-positive

• History of, or concurrent hepatocellular carcinoma

• History of, or concurrent depression, schizophrenia, or suicide attempt in the past

• Pregnant, lactating, or suspected pregnant patients, or male patients whose female partner is pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Toranomon Hospital	Kawasaki City	Takatsu-ku	Japan	213-8587

Sponsors and Collaborators

• Mitsubishi Tanabe Pharma Corporation

Investigators

• Study Director: Kazuoki Kondo, M.D., Mitsubishi Tanabe Pharma Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT01753557
• Other Study ID Numbers: G060-A12
• First Posted: Dec 20, 2012
• Last Update Posted: Oct 3, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Mitsubishi Tanabe Pharma Corporation: Pegasys
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Interferon alpha-2; Peginterferon alfa-2a

Study Results

Participant Flow

Arm/Group Title	Treatment-Naive	Treatment-Relapsed
Arm/Group Description	Drug: MP-424 (generic name:Telaprevir) 750mg every 8 hours(q8h) for 12 weeks Drug: RBV (Ribavirin) 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks	Drug: MP-424 (generic name:Telaprevir) 750mg every 8 hours(q8h) for 12 weeks Drug: RBV (Ribavirin) 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks
Period Title: Overall Study
STARTED	35	19
COMPLETED	35	19
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Treatment-Naive	Treatment-Relapsed	Total
Arm/Group Description	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks	Total of all reporting groups
Overall Participants	35	19	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.7 (10.5)	54.3 (9.5)	52.6 (10.1)
Sex: Female, Male (Count of Participants)
Female	9 25.7%	9 47.4%	18 33.3%
Male	26 74.3%	10 52.6%	36 66.7%

Outcome Measures

1. Primary Outcome

Title	Undetectable HCV (Hepatitis C Virus) RNA (Ribonucleic Acid) at 24 Weeks After Completion of Drug Administration (SVR, Sustained Viral Response)
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment-Naive	Treatment-Relapsed
Arm/Group Description	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks
Measure Participants	35	19
Number (95% Confidence Interval) [percentage of subjects achieving SVR]	85.7	94.7

2. Secondary Outcome

Title	Undetectable HCV RNA at 4 Weeks After Beginning of Drug Administration (RVR, Rapid Viral Response)
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment-Naive	Treatment-Relapsed
Arm/Group Description	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks
Measure Participants	35	19
Number (95% Confidence Interval) [percentage of subjects achieving RVR]	88.6	100.0

3. Secondary Outcome

Title	Undetectable HCV RNA at Completion of Drug Administration (ETR, End-of-treatment Response)
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment-Naive	Treatment-Relapsed
Arm/Group Description	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks
Measure Participants	35	19
Number (95% Confidence Interval) [percentage of subjects achieving ETR]	97.1	100.0

4. Secondary Outcome

Title	Undetectable HCV RNA at 12 Weeks After Completion of Drug Administration
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment-Naive	Treatment-Relapsed
Arm/Group Description	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks
Measure Participants	35	19
Number (95% Confidence Interval) [percentage of subjects achieving SVR12]	82.9	94.7

5. Secondary Outcome

Title	Transition of Serum HCV RNA Levels
Time Frame	baseline，Day2，Day3，1Weeks，2Weeks，3Weeks，4Weeks，End of treatment，Follow-up 12weeks，Follow-up 24weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment-Naive	Treatment-Relapsed
Arm/Group Description	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks
Measure Participants	35	19
baseline (n=35,19)	6.70	7.05
Day2 (n=35,19)	3.80	4.00
Day3 (n=35,19)	3.10	3.30
1Weeks (n=35,19)	2.00	2.00
2Weeks (n=34,19)	1.00	1.00
3Weeks (n=35,19)	0.50	0.50
4Weeks (n=35,19)	0.50	0.50
End of treatment (n=35,19)	0.50	0.50
Follow-up 12Weeks (n=33,19)	0.50	0.50
Follow-up 24Weeks (n=35,19)	0.50	0.50

6. Secondary Outcome

Title	Viral Sequencing at the Non-structural 3 Protease Region of HCV Virus（Result of Resistance-associated Variants Analysis)
Time Frame	From baseline to 24 weeks after completion of drug administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment-Naïve	Treatment-Relapsed
Arm/Group Description	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks
Measure Participants	4	1
V36A	1 2.9%	0 0%
T54A	0 0%	1 5.3%
Not detected	3 8.6%	0 0%

Adverse Events

Arm/Group Title	Treatment-Naive		Treatment-Relapsed
Arm/Group Description	Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks		Drug: MP-424 750mg q8h for 12 weeks Drug: RBV 600 - 1000 mg/day based on body weight for 24 weeks Drug: PEG-IFN alfa-2a 180mcg/kg/week for 24 weeks
All Cause Mortality
	Treatment-Naive		Treatment-Relapsed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment-Naive		Treatment-Relapsed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		2/19 (10.5%)
Musculoskeletal and connective tissue disorders
Synovial cyst	0/35 (0%)		1/19 (5.3%)
Skin and subcutaneous tissue disorders
Pruritus generalised	0/35 (0%)		1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	Treatment-Naive		Treatment-Relapsed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/35 (100%)		19/19 (100%)
Blood and lymphatic system disorders
Anaemia	33/35 (94.3%)		19/19 (100%)
Ear and labyrinth disorders
Vertigo	2/35 (5.7%)		0/19 (0%)
Ear pain	1/35 (2.9%)		1/19 (5.3%)
Cerumen impaction	0/35 (0%)		1/19 (5.3%)
Endocrine disorders
Hypothyroidism	2/35 (5.7%)		2/19 (10.5%)
Eye disorders
Retinopathy	8/35 (22.9%)		0/19 (0%)
Vision blurred	1/35 (2.9%)		1/19 (5.3%)
Asthenopia	2/35 (5.7%)		0/19 (0%)
Eye pain	2/35 (5.7%)		0/19 (0%)
Dry eye	1/35 (2.9%)		1/19 (5.3%)
Retinal haemorrhage	1/35 (2.9%)		1/19 (5.3%)
Cataract	0/35 (0%)		1/19 (5.3%)
Eye discharge	0/35 (0%)		1/19 (5.3%)
Punctate keratitis	0/35 (0%)		1/19 (5.3%)
Retinal vein occlusion	0/35 (0%)		1/19 (5.3%)
Eye pruritus	0/35 (0%)		1/19 (5.3%)
Gastrointestinal disorders
Diarrhoea	8/35 (22.9%)		3/19 (15.8%)
Nausea	7/35 (20%)		9/19 (47.4%)
Stomatitis	5/35 (14.3%)		7/19 (36.8%)
Vomiting	5/35 (14.3%)		3/19 (15.8%)
Abdominal discomfort	4/35 (11.4%)		1/19 (5.3%)
Constipation	2/35 (5.7%)		2/19 (10.5%)
Dyspepsia	2/35 (5.7%)		0/19 (0%)
Cheilitis	1/35 (2.9%)		2/19 (10.5%)
Abdominal pain lower	0/35 (0%)		1/19 (5.3%)
Abdominal pain upper	0/35 (0%)		1/19 (5.3%)
Glossitis	0/35 (0%)		1/19 (5.3%)
Oral pain	0/35 (0%)		1/19 (5.3%)
Proctalgia	0/35 (0%)		1/19 (5.3%)
General disorders
Pyrexia	20/35 (57.1%)		10/19 (52.6%)
Malaise	16/35 (45.7%)		12/19 (63.2%)
Injection site erythema	14/35 (40%)		3/19 (15.8%)
Injection site reaction	4/35 (11.4%)		4/19 (21.1%)
Thirst	2/35 (5.7%)		2/19 (10.5%)
Oedema peripheral	2/35 (5.7%)		0/19 (0%)
Feeling hot	1/35 (2.9%)		1/19 (5.3%)
Hepatobiliary disorders
Hepatic function abnormal	0/35 (0%)		4/19 (21.1%)
Hepatic steatosis	0/35 (0%)		2/19 (10.5%)
Hyperbilirubinaemia	0/35 (0%)		1/19 (5.3%)
Infections and infestations
Nasopharyngitis	14/35 (40%)		6/19 (31.6%)
Periodontitis	3/35 (8.6%)		2/19 (10.5%)
Urinary tract infection	1/35 (2.9%)		1/19 (5.3%)
Folliculitis	1/35 (2.9%)		1/19 (5.3%)
Hordeolum	1/35 (2.9%)		1/19 (5.3%)
Cystitis	0/35 (0%)		3/19 (15.8%)
Oral herpes	0/35 (0%)		2/19 (10.5%)
Furuncle	0/35 (0%)		1/19 (5.3%)
Herpes simplex	0/35 (0%)		1/19 (5.3%)
Influenza	0/35 (0%)		1/19 (5.3%)
Pharyngitis	0/35 (0%)		1/19 (5.3%)
Enterocolitis viral	0/35 (0%)		1/19 (5.3%)
Injury, poisoning and procedural complications
Arthropod sting	1/35 (2.9%)		1/19 (5.3%)
Arthropod bite	0/35 (0%)		1/19 (5.3%)
Investigations
White blood cell count decreased	29/35 (82.9%)		14/19 (73.7%)
Platelet count decreased	29/35 (82.9%)		13/19 (68.4%)
Blood uric acid increased	21/35 (60%)		6/19 (31.6%)
Blood creatinine increased	18/35 (51.4%)		5/19 (26.3%)
Blood bilirubin increased	8/35 (22.9%)		2/19 (10.5%)
Blood triglycerides increased	6/35 (17.1%)		1/19 (5.3%)
Hyaluronic acid increased	5/35 (14.3%)		4/19 (21.1%)
Blood potassium decreased	2/35 (5.7%)		1/19 (5.3%)
Liver function test abnormal	3/35 (8.6%)		0/19 (0%)
Neutrophil count decreased	3/35 (8.6%)		0/19 (0%)
Gamma-glutamyltransferase increased	1/35 (2.9%)		2/19 (10.5%)
Blood lactate dehydrogenase increased	1/35 (2.9%)		1/19 (5.3%)
Lymphocyte count decreased	1/35 (2.9%)		1/19 (5.3%)
Blood phosphorus decreased	1/35 (2.9%)		1/19 (5.3%)
Blood alkaline phosphatase increased	1/35 (2.9%)		1/19 (5.3%)
Bilirubin conjugated increased	0/35 (0%)		1/19 (5.3%)
Metabolism and nutrition disorders
Hyperuricaemia	7/35 (20%)		8/19 (42.1%)
Decreased appetite	6/35 (17.1%)		11/19 (57.9%)
Lipid metabolism disorder	0/35 (0%)		1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/35 (14.3%)		7/19 (36.8%)
Muscle spasms	2/35 (5.7%)		0/19 (0%)
Nervous system disorders
Headache	15/35 (42.9%)		8/19 (42.1%)
Dysgeusia	7/35 (20%)		4/19 (21.1%)
Hypoaesthesia	2/35 (5.7%)		0/19 (0%)
Dizziness	0/35 (0%)		2/19 (10.5%)
Migraine	0/35 (0%)		1/19 (5.3%)
Presyncope	0/35 (0%)		1/19 (5.3%)
Psychiatric disorders
Insomnia	6/35 (17.1%)		5/19 (26.3%)
Depressive symptom	1/35 (2.9%)		1/19 (5.3%)
Renal and urinary disorders
Renal impairment	3/35 (8.6%)		2/19 (10.5%)
Pollakiuria	0/35 (0%)		1/19 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/35 (5.7%)		5/19 (26.3%)
Oropharyngeal pain	1/35 (2.9%)		1/19 (5.3%)
Skin and subcutaneous tissue disorders
Rash	13/35 (37.1%)		6/19 (31.6%)
Drug eruption	11/35 (31.4%)		2/19 (10.5%)
Alopecia	9/35 (25.7%)		5/19 (26.3%)
Pruritus	5/35 (14.3%)		1/19 (5.3%)
Rash maculo-papular	2/35 (5.7%)		3/19 (15.8%)
Pruritus generalised	2/35 (5.7%)		2/19 (10.5%)
Dry skin	2/35 (5.7%)		1/19 (5.3%)
Palmoplantar keratoderma	1/35 (2.9%)		2/19 (10.5%)
Dyshidrotic eczema	1/35 (2.9%)		1/19 (5.3%)
Eczema asteatotic	0/35 (0%)		2/19 (10.5%)
Erythema	0/35 (0%)		1/19 (5.3%)
Erythema multiforme	0/35 (0%)		1/19 (5.3%)
Papule	0/35 (0%)		1/19 (5.3%)
Photosensitivity reaction	0/35 (0%)		1/19 (5.3%)
Vascular disorders
Hypertension	1/35 (2.9%)		1/19 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.