K4 Elite
K4 Elite
Thymosin alpha-1 is a 28-amino-acid thymic peptide marketed as thymalfasin (Zadaxin, SciClone) and reported to be approved in more than 35 countries, chiefly for chronic hepatitis B and C and as an immune adjuvant; it has no FDA-approved labeling in the United States (no entry in DailyMed) although it carries US orphan-drug designations. Randomized trials, mostly from the 1990s-2000s and largely in Asia and Italy, used 1.6 mg subcutaneously twice weekly for 6-12 months in hepatitis B, in combination with interferon in hepatitis C, and as an adjunct in severe sepsis (ETASS, n=361). Adverse-event reporting across these trials is limited but consistently describes injection-site discomfort as the main event.
Each row records what a published study did: who it enrolled, the regimen it administered to those subjects, and what it reported. These are historical study descriptions, not protocols to follow.
| Study | Population | Regimen as reported | Primary findings |
|---|---|---|---|
| Chien et al., Hepatology 1998 (randomized controlled, Taiwan) | 98 patients with clinicopathologically proven chronic hepatitis B | Patients received thymosin alpha-1 1.6 mg subcutaneously twice weekly for 26 weeks (group A) or 52 weeks (group B), or no specific treatment (group C), with 18-month follow-up. | Complete virological response (HBV DNA and HBeAg clearance) at 18 months was 40.6% (26-week group), 26.5% (52-week group) and 9.4% (controls); no responder lost HBsAg and no significant side effects were observed. |
| Mutchnick et al., J Viral Hepat 1999 (phase III, multicentre, double-blind, placebo-controlled) | 97 patients with HBV DNA- and HBeAg-positive chronic hepatitis B (thymosin n=49; placebo n=48) | Patients received thymosin alpha-1 1.6 mg or placebo subcutaneously twice weekly for 6 months, followed by 6 months of observation. | Complete response (sustained HBV DNA negativity with negative HBeAg at month 12) occurred in 7 (14%) thymosin vs 2 (4%) placebo patients (p=0.084), i.e., not statistically significant. |
| Andreone et al., Hepatology 1996 (randomized vs interferon alfa, Italy) | 33 patients with anti-HBe-positive, HBV-DNA-positive chronic hepatitis B (thymosin n=17; interferon n=16) | Patients received thymosin alpha-1 900 mcg/m2 body surface area subcutaneously twice weekly, or interferon alfa 5 MU three times weekly, for 6 months. | Complete response was 29.4% (thymosin) vs 43.8% (interferon) at end of treatment and 41.2% vs 25% after 6 months' follow-up (not significant); thymosin was tolerated by all patients with local injection-site discomfort the only reported side effect. |
| Iino et al., J Viral Hepat 2005 (randomized dose-comparison, Japan) | 316 patients with chronic hepatitis B, HBV DNA-positive with elevated ALT | Patients were randomized to thymosin alpha-1 0.8 mg or 1.6 mg monotherapy (subcutaneous) for 24 weeks with observation to week 72. | At week 72, 36.4% of the 1.6-mg group had ALT normalisation, 30% HBV DNA clearance (bDNA) and 22.8% HBeAg clearance, with similar rates at 0.8 mg; all adverse drug reactions were mild and mostly liver-enzyme fluctuations, with similar incidence between doses. |
| Sherman et al., Hepatology 1998 (randomized, double-blind, placebo-controlled; hepatitis C) | 109 patients with biopsy-confirmed chronic hepatitis C | Patients received thymosin alpha-1 1.6 mg subcutaneously twice weekly plus interferon alfa 3 MU three times weekly, interferon plus placebo thymosin, or double placebo, for 26 weeks. | End-of-treatment biochemical response was 37.1% (combination), 16.2% (interferon alone) and 2.7% (placebo) (p=0.04 for combination vs interferon); HCV RNA clearance was 37.1% vs 18.9%; sustained biochemical response was 14.2% vs 8.1%. |
| Wu et al., Crit Care 2013 — ETASS (multicentre, single-blind, randomized controlled; China) Registry: NCT00711620
|
361 ICU patients with severe sepsis (thymosin n=181; control n=180) | Patients received thymosin alpha-1 in addition to conventional sepsis therapy, or conventional therapy alone (dose and schedule not stated in the abstract). | 28-day all-cause mortality was 26.0% with thymosin vs 35.0% in controls (RR 0.74, 95% CI 0.54-1.02; p=0.062 unstratified, log-rank p=0.049); monocyte HLA-DR improved more in the thymosin group; no serious drug-related adverse event was recorded. |
| Zhang et al., Clin Infect Dis 2008 (prospective randomized, thymosin plus ulinastatin; China) | 120 patients with sepsis from intra-abdominal infection due to carbapenem-resistant bacteria (60 per arm) | Patients received carbapenems plus thymosin alpha-1 and ulinastatin, or carbapenems plus placebo. | The combination group had better organ-failure scores and cumulative survival exceeding the control group by 17.8% at day 28, 25.9% at day 60 and 27.4% at day 90; thymosin's independent contribution cannot be separated from ulinastatin. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| Local injection-site discomfort | The only side effect reported, by some of 17 patients receiving 900 mcg/m2 twice weekly for 6 months (Andreone 1996). | A randomized controlled trial of thymosin-alpha1 versus interferon alfa treatment in patients with HBeAb- and HBV DNA-positive chronic hepatitis B ↗ |
| Liver-enzyme (ALT) fluctuations | Most adverse drug reactions in 316 Japanese CHB patients were mild ALT fluctuations, interpreted by the authors as immune-response related; incidence similar at 0.8 and 1.6 mg (Iino 2005). | The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial ↗ |
| No significant side effects / no serious drug-related adverse events | Reported in 98 CHB patients (Chien 1998) and in 181 severe-sepsis patients (ETASS, Wu 2013). | The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial ↗ |
Interactions documented in trial reports, prescribing information or pharmacology references.
| Agent | Type | Note | Source |
|---|---|---|---|
| Interferon alfa | pharmacodynamic (studied combination) | Thymosin alpha-1 was co-administered with interferon alfa in randomized hepatitis C (Sherman 1998) and open-label hepatitis B/C studies (Rasi 1996); no adverse pharmacokinetic interaction was described, and combination arms had higher response rates than interferon alone in Sherman 1998. | Combination therapy with thymosin alpha1 and interferon for the treatment of chronic hepatitis C infection ↗ |
Exclusions and label contraindications recorded in the cited sources.