Gastroenterology · Clinical trials
Hepatitis C Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About hepatitis c — and why its trials are hard
Chronic hepatitis C virus (HCV) infection was transformed from a hard-to-treat disease requiring interferon into a curable condition by direct-acting antivirals (DAAs). Interferon-based regimens produced modest cure rates with substantial toxicity, and first-generation protease inhibitors added in 2011 (telaprevir, boceprevir) still required interferon and ribavirin. The breakthrough came with sofosbuvir, an NS5B nucleotide polymerase inhibitor, followed by combination DAAs targeting NS5A and NS3/4A. Modern pangenotypic, interferon-free, once-daily oral regimens achieve sustained virologic response at 12 weeks (SVR12)-defined as undetectable HCV RNA-in roughly 95-99% of patients across genotypes, including cirrhotics and prior treatment failures, over 8-12 week courses. SVR12 equates to virologic cure and reduces cirrhosis, hepatocellular carcinoma, and mortality risk. The remaining challenges are largely non-pharmacologic: diagnosis, linkage to care, access, and reinfection prevention. The development graveyard includes agents halted for toxicity, notably the nucleotide BMS-986094, underscoring the narrow safety margins of early nucleotide chemistry.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Sofosbuvir (Sovaldi) | 2013 | Chronic HCV; NS5B nucleotide polymerase inhibitor (backbone of many regimens) | NEUTRINO (with peginterferon/ribavirin), FISSION | SVR12 | ~90% SVR12 in NEUTRINO (genotypes 1, 4, 5, 6) |
| Ledipasvir/sofosbuvir (Harvoni) | 2014 | Genotype 1 (and others) HCV; NS5A inhibitor plus NS5B inhibitor, interferon-free | ION-1, ION-2, ION-3 | SVR12 | ~94-99% SVR12 |
| Sofosbuvir/velpatasvir (Epclusa) | 2016 | Pangenotypic HCV (all genotypes 1-6); NS5A plus NS5B inhibitor | ASTRAL-1, ASTRAL-2, ASTRAL-3 | SVR12 | ~98-99% SVR12 across genotypes |
| Glecaprevir/pibrentasvir (Mavyret) | 2017 | Pangenotypic HCV; NS3/4A protease inhibitor plus NS5A inhibitor, 8-week option for treatment-naive without cirrhosis | ENDURANCE, SURVEYOR, EXPEDITION programs | SVR12 | ~98% SVR12 |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in hepatitis c development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| BMS-986094 (formerly INX-189) — Phase 2b (NS5B nucleotide polymerase inhibitor) | Development halted in August 2012 after serious cardiac and renal toxicity, including a patient death from heart failure | Off-target mitochondrial/cardiotoxicity of the nucleotide prodrug; the safety catastrophe reshaped how nucleotide analogs were screened |
| Faldaprevir (BI 201335) — STARTVerso phase 3 (NS3/4A protease inhibitor with peginterferon/ribavirin) | Achieved reasonable SVR rates but development was discontinued in 2014 | Interferon-free all-oral DAA combinations rendered an interferon-dependent protease inhibitor therapeutically and commercially obsolete |
Choosing the right endpoint
Primary endpoints that matter in hepatitis c trials
- SVR12 — Undetectable HCV RNA 12 weeks after treatment end; the accepted surrogate for virologic cure.
- SVR24 — Sustained response at 24 weeks, used in earlier trials; concordant with SVR12 in nearly all cases.
- On-treatment virologic failure/relapse — Breakthrough or post-treatment relapse, often linked to resistance-associated substitutions.
- Clinical/long-term outcomes — SVR is associated with reduced cirrhosis progression, hepatocellular carcinoma, and all-cause mortality.
How iNGENū runs hepatitis c trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Hepatitis C clinical trials — FAQs
Does achieving SVR12 mean the patient is cured?
Are DAAs effective across all HCV genotypes?
Can someone be reinfected after cure?
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