Trial Outcomes & Findings for Extended Treatment With PEG-Intron® and Rebetol® in Patients With Genotype 1 Chronic Hepatitis C and Slow Virologic Response (Study P03685) (NCT NCT00265395)
NCT ID: NCT00265395
Last Updated: 2017-04-05
Results Overview
LLQ = 30 IU/mL by reverse transcription polymerase chain reaction (RT-PCR) (Taqman Roche)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1428 participants
Primary outcome timeframe
48 or 72 weeks of treatment plus 24 weeks of follow-up.
Results posted on
2017-04-05
Participant Flow
1428 patients enrolled; 159 patients qualified as slow responders per treatment week 12 and 24 protocol-specified eligibility criteria; 159 patients were randomized
Participant milestones
| Measure |
Standard Therapy (48-week Treatment)
Slow responders (defined as being polymerase chain reaction \[PCR\] positive at Week 12 with at least 2 log reduction in viral load and PCR negative at Week 24) who are randomized at Week 48 to stop treatment at Week 48.
|
Extended Therapy (72-week Treatment)
Slow responders (defined as being PCR positive at Week 12 with at least 2 log reduction in viral load and PCR negative at Week 24) who are randomized at Week 48 to continue treatment to Week 72.
|
|---|---|---|
|
Overall Study
STARTED
|
86
|
73
|
|
Overall Study
COMPLETED
|
78
|
56
|
|
Overall Study
NOT COMPLETED
|
8
|
17
|
Reasons for withdrawal
| Measure |
Standard Therapy (48-week Treatment)
Slow responders (defined as being polymerase chain reaction \[PCR\] positive at Week 12 with at least 2 log reduction in viral load and PCR negative at Week 24) who are randomized at Week 48 to stop treatment at Week 48.
|
Extended Therapy (72-week Treatment)
Slow responders (defined as being PCR positive at Week 12 with at least 2 log reduction in viral load and PCR negative at Week 24) who are randomized at Week 48 to continue treatment to Week 72.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
6
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
6
|
|
Overall Study
Protocol Violation
|
2
|
2
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
|
Overall Study
Administrative
|
0
|
1
|
Baseline Characteristics
Extended Treatment With PEG-Intron® and Rebetol® in Patients With Genotype 1 Chronic Hepatitis C and Slow Virologic Response (Study P03685)
Baseline characteristics by cohort
| Measure |
Standard Therapy (48-week Treatment)
n=86 Participants
Slow responders (defined as being polymerase chain reaction \[PCR\] positive at Week 12 with at least 2 log reduction in viral load and PCR negative at Week 24) who are randomized at Week 48 to stop treatment at Week 48.
|
Extended Therapy (72-week Treatment)
n=73 Participants
Slow responders (defined as being PCR positive at Week 12 with at least 2 log reduction in viral load and PCR negative at Week 24) who are randomized at Week 48 to continue treatment to Week 72.
|
Total
n=159 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
44.5 years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
46.5 years
STANDARD_DEVIATION 11.6 • n=7 Participants
|
45.35 years
STANDARD_DEVIATION 10.79 • n=5 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
52 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
98 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 or 72 weeks of treatment plus 24 weeks of follow-up.Population: According to the protocol, the efficacy analysis was carried out on all slow responders (ie, patients who had at least 2 log drop in HCV-RNA level at treatment week 12, and undetectable HCV-RNA at treatment week 24).
LLQ = 30 IU/mL by reverse transcription polymerase chain reaction (RT-PCR) (Taqman Roche)
Outcome measures
| Measure |
Standard Therapy (48-week Treatment)
n=86 Participants
Slow responders (defined as being polymerase chain reaction \[PCR\] positive at Week 12 with at least 2 log reduction in viral load and PCR negative at Week 24) who are randomized at Week 48 to stop treatment at Week 48.
|
Extended Therapy (72-week Treatment)
n=73 Participants
Slow responders (defined as being PCR positive at Week 12 with at least 2 log reduction in viral load and PCR negative at Week 24) who are randomized at Week 48 to continue treatment to Week 72.
|
|---|---|---|
|
Sustained Virologic Response, Defined as a Plasma HCV-RNA (Hepatitis C Ribonucleic Acid) Level Below the LLQ (Lower Level of Quantitation) at 24 Weeks Post-treatment.
|
37 Participants
|
35 Participants
|
Adverse Events
Standard Therapy (48-week Treatment)
Serious events: 93 serious events
Other events: 1337 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Standard Therapy (48-week Treatment)
n=1427 participants at risk
|
|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.14%
2/1427 • Number of events 2
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
0.07%
1/1427 • Number of events 1
|
|
Blood and lymphatic system disorders
PANCYTOPENIA
|
0.07%
1/1427 • Number of events 1
|
|
Cardiac disorders
ATRIOVENTRICULAR BLOCK COMPLETE
|
0.07%
1/1427 • Number of events 1
|
|
Cardiac disorders
ATRIOVENTRICULAR BLOCK SECOND DEGREE
|
0.07%
1/1427 • Number of events 1
|
|
Cardiac disorders
BRADYCARDIA
|
0.14%
2/1427 • Number of events 2
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.07%
1/1427 • Number of events 1
|
|
Cardiac disorders
PALPITATIONS
|
0.07%
1/1427 • Number of events 1
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
0.07%
1/1427 • Number of events 1
|
|
Cardiac disorders
SINUS BRADYCARDIA
|
0.07%
1/1427 • Number of events 1
|
|
Ear and labyrinth disorders
VERTIGO
|
0.14%
2/1427 • Number of events 2
|
|
Endocrine disorders
AUTOIMMUNE THYROIDITIS
|
0.07%
1/1427 • Number of events 1
|
|
Endocrine disorders
HYPERTHYROIDISM
|
0.14%
2/1427 • Number of events 2
|
|
Endocrine disorders
HYPOTHYROIDISM
|
0.07%
1/1427 • Number of events 1
|
|
Endocrine disorders
THYROIDITIS SUBACUTE
|
0.07%
1/1427 • Number of events 1
|
|
Eye disorders
RETINAL DETACHMENT
|
0.07%
1/1427 • Number of events 1
|
|
Eye disorders
RETINAL TEAR
|
0.07%
1/1427 • Number of events 1
|
|
Eye disorders
VISUAL DISTURBANCE
|
0.07%
1/1427 • Number of events 1
|
|
Gastrointestinal disorders
ABDOMINAL PAIN LOWER
|
0.07%
1/1427 • Number of events 1
|
|
Gastrointestinal disorders
COLITIS ULCERATIVE
|
0.07%
1/1427 • Number of events 1
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.07%
1/1427 • Number of events 1
|
|
Gastrointestinal disorders
GASTRITIS EROSIVE
|
0.07%
1/1427 • Number of events 1
|
|
Gastrointestinal disorders
INTESTINAL OBSTRUCTION
|
0.07%
1/1427 • Number of events 1
|
|
Gastrointestinal disorders
INTUSSUSCEPTION
|
0.07%
1/1427 • Number of events 1
|
|
Gastrointestinal disorders
NAUSEA
|
0.28%
4/1427 • Number of events 4
|
|
Gastrointestinal disorders
PANCREATITIS NECROTISING
|
0.07%
1/1427 • Number of events 1
|
|
Gastrointestinal disorders
SMALL INTESTINAL OBSTRUCTION
|
0.07%
1/1427 • Number of events 1
|
|
Gastrointestinal disorders
VOLVULUS
|
0.07%
1/1427 • Number of events 1
|
|
Gastrointestinal disorders
VOMITING
|
0.07%
1/1427 • Number of events 1
|
|
General disorders
ASTHENIA
|
0.28%
4/1427 • Number of events 5
|
|
General disorders
PAIN
|
0.07%
1/1427 • Number of events 1
|
|
General disorders
PYREXIA
|
0.07%
1/1427 • Number of events 1
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.07%
1/1427 • Number of events 1
|
|
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
|
0.07%
1/1427 • Number of events 1
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.07%
1/1427 • Number of events 1
|
|
Hepatobiliary disorders
JAUNDICE
|
0.07%
1/1427 • Number of events 1
|
|
Immune system disorders
HYPERSENSITIVITY
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
ABSCESS LIMB
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
ABSCESS ORAL
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
APPENDICITIS
|
0.28%
4/1427 • Number of events 4
|
|
Infections and infestations
CELLULITIS
|
0.14%
2/1427 • Number of events 2
|
|
Infections and infestations
CYTOMEGALOVIRUS INFECTION
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
INFLUENZA
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
INJECTION SITE ABSCESS
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
INJECTION SITE CELLULITIS
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
LOBAR PNEUMONIA
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
ORCHITIS
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
PNEUMONIA
|
0.28%
4/1427 • Number of events 4
|
|
Infections and infestations
PULMONARY TUBERCULOSIS
|
0.14%
2/1427 • Number of events 2
|
|
Infections and infestations
PYELONEPHRITIS
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
SALMONELLOSIS
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
SEPTIC SHOCK
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
SYPHILIS
|
0.07%
1/1427 • Number of events 1
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
ALCOHOL POISONING
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
CLAVICLE FRACTURE
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
CONCUSSION
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
CONTUSION
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
DISLOCATION OF VERTEBRA
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
DRUG TOXICITY
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
INJURY
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
MULTIPLE DRUG OVERDOSE INTENTIONAL
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
ROAD TRAFFIC ACCIDENT
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
SCAPULA FRACTURE
|
0.07%
1/1427 • Number of events 1
|
|
Injury, poisoning and procedural complications
UPPER LIMB FRACTURE
|
0.07%
1/1427 • Number of events 1
|
|
Investigations
ARTERIOGRAM
|
0.07%
1/1427 • Number of events 1
|
|
Investigations
HEART RATE INCREASED
|
0.07%
1/1427 • Number of events 1
|
|
Investigations
PLATELET COUNT DECREASED
|
0.07%
1/1427 • Number of events 1
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
0.07%
1/1427 • Number of events 1
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
0.07%
1/1427 • Number of events 2
|
|
Metabolism and nutrition disorders
HYPERCALCAEMIA
|
0.07%
1/1427 • Number of events 1
|
|
Metabolism and nutrition disorders
HYPOGLYCAEMIA
|
0.07%
1/1427 • Number of events 1
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.07%
1/1427 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
0.07%
1/1427 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
ARTHRITIS
|
0.07%
1/1427 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.07%
1/1427 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
UNEQUAL LIMB LENGTH
|
0.07%
1/1427 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CERVIX CARCINOMA
|
0.07%
1/1427 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HEPATIC NEOPLASM MALIGNANT
|
0.14%
2/1427 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PARATHYROID TUMOUR BENIGN
|
0.07%
1/1427 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
UTERINE LEIOMYOMA
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
CAROTID ARTERY DISSECTION
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
CAROTID ARTERY OCCLUSION
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
CEREBRAL INFARCTION
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
CONVULSION
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
EPILEPSY
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
GRAND MAL CONVULSION
|
0.14%
2/1427 • Number of events 2
|
|
Nervous system disorders
HEADACHE
|
0.14%
2/1427 • Number of events 2
|
|
Nervous system disorders
MEMORY IMPAIRMENT
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
MIGRAINE
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
NERVOUS SYSTEM DISORDER
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
PARKINSONISM
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
SYNCOPE
|
0.21%
3/1427 • Number of events 3
|
|
Nervous system disorders
SYNCOPE VASOVAGAL
|
0.07%
1/1427 • Number of events 1
|
|
Nervous system disorders
TREMOR
|
0.07%
1/1427 • Number of events 1
|
|
Pregnancy, puerperium and perinatal conditions
ABORTION SPONTANEOUS
|
0.07%
1/1427 • Number of events 1
|
|
Psychiatric disorders
ALCOHOLISM
|
0.07%
1/1427 • Number of events 1
|
|
Psychiatric disorders
ANXIETY
|
0.07%
1/1427 • Number of events 1
|
|
Psychiatric disorders
BIPOLAR DISORDER
|
0.07%
1/1427 • Number of events 1
|
|
Psychiatric disorders
COMPLETED SUICIDE
|
0.14%
2/1427 • Number of events 2
|
|
Psychiatric disorders
DELIRIUM
|
0.07%
1/1427 • Number of events 1
|
|
Psychiatric disorders
DEPRESSION
|
0.28%
4/1427 • Number of events 4
|
|
Psychiatric disorders
HALLUCINATION, AUDITORY
|
0.07%
1/1427 • Number of events 1
|
|
Psychiatric disorders
HALLUCINATION, VISUAL
|
0.07%
1/1427 • Number of events 1
|
|
Psychiatric disorders
HOMICIDAL IDEATION
|
0.07%
1/1427 • Number of events 1
|
|
Psychiatric disorders
PANIC ATTACK
|
0.14%
2/1427 • Number of events 2
|
|
Psychiatric disorders
PARANOIA
|
0.14%
2/1427 • Number of events 2
|
|
Psychiatric disorders
PSYCHOTIC DISORDER
|
0.14%
2/1427 • Number of events 2
|
|
Psychiatric disorders
SUICIDAL IDEATION
|
0.07%
1/1427 • Number of events 1
|
|
Psychiatric disorders
SUICIDE ATTEMPT
|
0.21%
3/1427 • Number of events 3
|
|
Renal and urinary disorders
OLIGURIA
|
0.07%
1/1427 • Number of events 1
|
|
Reproductive system and breast disorders
METRORRHAGIA
|
0.07%
1/1427 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHITIS CHRONIC
|
0.07%
1/1427 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA EXERTIONAL
|
0.07%
1/1427 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPNEUMOTHORAX
|
0.07%
1/1427 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
0.07%
1/1427 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
INTERSTITIAL LUNG DISEASE
|
0.07%
1/1427 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
OBLITERATIVE BRONCHIOLITIS
|
0.07%
1/1427 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
ECZEMA NUMMULAR
|
0.07%
1/1427 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
SKIN LESION
|
0.07%
1/1427 • Number of events 1
|
|
Surgical and medical procedures
ANAL FISSURE EXCISION
|
0.07%
1/1427 • Number of events 1
|
|
Vascular disorders
THROMBOSIS
|
0.07%
1/1427 • Number of events 1
|
Other adverse events
| Measure |
Standard Therapy (48-week Treatment)
n=1427 participants at risk
|
|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
13.8%
197/1427 • Number of events 260
|
|
Blood and lymphatic system disorders
ERYTHROPENIA
|
5.2%
74/1427 • Number of events 96
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
12.8%
183/1427 • Number of events 268
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
19.7%
281/1427 • Number of events 464
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
6.6%
94/1427 • Number of events 112
|
|
Gastrointestinal disorders
DIARRHOEA
|
9.0%
129/1427 • Number of events 152
|
|
Gastrointestinal disorders
DRY MOUTH
|
5.3%
75/1427 • Number of events 75
|
|
Gastrointestinal disorders
NAUSEA
|
17.8%
254/1427 • Number of events 301
|
|
General disorders
ASTHENIA
|
28.2%
402/1427 • Number of events 458
|
|
General disorders
CHILLS
|
10.7%
153/1427 • Number of events 204
|
|
General disorders
FATIGUE
|
23.7%
338/1427 • Number of events 412
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
42.0%
599/1427 • Number of events 843
|
|
General disorders
INJECTION SITE ERYTHEMA
|
10.0%
143/1427 • Number of events 152
|
|
General disorders
IRRITABILITY
|
11.0%
157/1427 • Number of events 169
|
|
General disorders
PYREXIA
|
29.5%
421/1427 • Number of events 834
|
|
Investigations
HAEMOGLOBIN DECREASED
|
11.3%
161/1427 • Number of events 215
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
7.4%
106/1427 • Number of events 171
|
|
Investigations
WEIGHT DECREASED
|
10.5%
150/1427 • Number of events 169
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
5.4%
77/1427 • Number of events 112
|
|
Metabolism and nutrition disorders
ANOREXIA
|
10.9%
156/1427 • Number of events 160
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
7.2%
103/1427 • Number of events 107
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
13.7%
195/1427 • Number of events 235
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
6.4%
91/1427 • Number of events 106
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
19.2%
274/1427 • Number of events 417
|
|
Nervous system disorders
DISTURBANCE IN ATTENTION
|
5.4%
77/1427 • Number of events 81
|
|
Nervous system disorders
DIZZINESS
|
8.1%
115/1427 • Number of events 128
|
|
Nervous system disorders
HEADACHE
|
28.6%
408/1427 • Number of events 569
|
|
Psychiatric disorders
DEPRESSION
|
9.7%
139/1427 • Number of events 156
|
|
Psychiatric disorders
INSOMNIA
|
12.5%
178/1427 • Number of events 194
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
13.7%
195/1427 • Number of events 213
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
7.8%
111/1427 • Number of events 124
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
22.3%
318/1427 • Number of events 328
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
13.2%
188/1427 • Number of events 199
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
18.7%
267/1427 • Number of events 290
|
|
Skin and subcutaneous tissue disorders
RASH
|
12.4%
177/1427 • Number of events 211
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60