Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AL-335 · 3 trials · 1 indication
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and up to 43 weeks that were absent before treatment or that worsened relative to pre-treatment state.
Body weight (measured using a calibrated scale) at end of treatment was reported.
BMI was calculated by dividing the body weight (in kilogram) by the square of height (in meters). BMI at end of treatment was reported.
Percentage of participants with worst post-baseline values of vital signs (Systolic blood pressure \[sBP\], Diastolic blood pressure \[dBP\], and Heart rate) were reported. For sBP, abnormally low: less than or equal to \[\<=\] 90 millimeters mercury \[mmHg\]; Grade 1 or mild: greater than \[\>\] 140 to less than \[\<\] 160 mmHg; Grade 2 or moderate: \>=160 to \<180 and Grade 3 or severe: \>=180 mmHg. For dBP, abnormally low: \<=50 mmHg; Grade 1 or mild: \>90 to \<100 mmHg; Grade 2 or moderate: \>=100 to \<110 mmHg and Grade 3 or severe: \>=110 mmHg. For Heart Rate, abnormally low: \<=50 beats per minute \[bpm\] and abnormally high: \>=120 bpm.
Percentage of participants with maximum decrease from baseline in mean ejection fraction was reported. Percentages are based on the number of participants with available data.
Percentage of participants by treatment emergent toxicity grade (1, 2, 3, 4 and 3+4) for Hematology parameters (hemoglobin, lymphocytes, neutrophils, leukocytes, platelets) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.
Percentage of participants by treatment emergent toxicity grade (Grade 1,2,3,4,3+4) for Blood Chemistry (Calcium, Phosphate, Potassium, Sodium, Bicarbonate, Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Direct bilirubin, Glucose, Cholesterol, Triglycerides, Urate, Triacylglycerol lipase, Creatinine, Creatinine clearance, Albumin and Creatine kinase) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.
Percentage of participants by treatment emergent toxicity grade for coagulation parameter (Prothrombin International Normalized Ratio) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.
Percentage of participants by treatment emergent toxicity grade (Grade 1, 2, 3, 4, 3+4) for urinalysis parameter (protein) was reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. A toxicity is treatment-emergent if it is worse than the baseline or if baseline is missing.
Percentage of participants with worst treatment emergent abnormalities of ECG parameters (Fridericia Corrected QT interval \[QTcF\], Bazett Corrected QT interval \[QTcB\], Heart rate, QRS and PR, was reported. For QTcF abnormality was defined as 30 milliseconds (ms) less than or equal to (\<=) QTcF increase from baseline \<= 60 ms; for QTcB abnormality was defined as 30 ms \<= QTcB increase from baseline \<= 60 ms; for heart rate - abnormal low: \<= 50 beats per minute (bpm) and abnormal high: \>= 120 bpm; for QRS - abnormal high: \>120 ms; for PR - abnormally low: PR \< 120 ms; abnormally high - 200 ms \< PR \<= 240 ms and 240 ms \< PR \<= 300 ms.
Tabulation of the number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG and abnormal clinical laboratory results (including chemistry, hematology, and urine).
To evaluate the effect of multiple oral doses of ACH-3102, on the multiple oral dose PK of AL-335 and metabolites
To evaluate the effect of multiple oral doses of Simeprevir, on the multiple oral dose PK of AL-335 and metabolites
To evaluate the effect of multiple oral doses of ACH-3102 and Simeprevir, on the multiple oral dose PK of AL-335 and metabolites
| Arm | Type | Description |
|---|---|---|
| Cohorts 1 and 2 (Without Cirrhosis) : AL-335+ODV+SMV | EXPERIMENTAL | Treatment-naïve non-cirrhotic Hepatitis C virus (HCV)-infected participants will receive AL-335 and Odalasvir (ODV) with Simeprevir (SMV) for 8 weeks. |
| Cohort 1b (Without Cirrhosis) : AL-335+ODV | EXPERIMENTAL | Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV for 8 weeks. |
| Cohort 3 (Without Cirrhosis) : AL-335+ODV+SMV | EXPERIMENTAL | Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV with SMV for 6 weeks. |
| Cohort 4 (Without Cirrhosis) : AL-335+ODV | EXPERIMENTAL | Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV up to 8 or 12 weeks. |
| Cohort 5 (Without Cirrhosis) : AL-335+ODV + SMV | EXPERIMENTAL | Treatment-naïve non-cirrhotic HCV-infected participants will receive AL-335 and ODV with SMV up to 8 or 12 weeks. |
| Cohorts 6, 7, 8 and 12 (With Cirrhosis) : AL-335+ODV+SMV | EXPERIMENTAL | Treatment naïve or treatment experienced HCV-infected participants with compensated cirrhosis will receive AL-335 and ODV with SMV for 8 weeks. |
| Cohorts 9, 10 and 11 (With Cirrhosis) : AL-335+ODV+SMV | EXPERIMENTAL | Treatment naïve or treatment experienced HCV-infected participants with compensated cirrhosis will receive AL-335 and ODV with SMV for 12 weeks. |
| Cohorts 12 to 15: AL-335+ODV With/without SMV | EXPERIMENTAL | Based on safety, pharmacokinetic (PK), and viral load data, the treatment duration (4 to 12 weeks) and dose levels (AL-335: 400-1,200 milligram \[mg\], ODV: 25-50 mg with/without SMV: 75-150 mg) may be changed for ongoing and future cohorts (up to 15) after obtaining agreement from the Sponsor and the Principal Investigator. |
| Placebo | PLACEBO_COMPARATOR | Placebo dosed once in human volunteers in increasing dosages or once daily for seven days in patients with chronic Hepatitis C in increasing dosages. |
| AL-335 | EXPERIMENTAL | AL-335 dosed once in human volunteers in increasing dosages or once daily for seven days in patients with chronic Hepatitis C in increasing dosages. |
| Group 1: AL-335, Simeprevir and ACH-3102 | ACTIVE_COMPARATOR | AL-335, ACH-3102, and Simeprevir dosed in healthy human volunteers once daily for 24 days. |
| Group 2: AL-335, Simeprevir and ACH-3102 | ACTIVE_COMPARATOR | AL-335, ACH-3102, and Simeprevir dosed in healthy human volunteers once daily for 24 days. |
| Name | Type | Description |
|---|---|---|
| AL-335 | DRUG | AL-335 tablets will be administered in a dose range of 400 to 1200 mg once daily (QD). |
| Odalasvir (ODV) | DRUG | ODV capsules will be administered in a dose range of 25 to 50 mg. |
| Simeprevir (SMV) | DRUG | SMV tablets will be administered in a dose range of 75 to 150 mg QD or every other day (QOD). |
| AL-335 matching placebo | DRUG | - |
| ACH-3102 | DRUG | ACH-3102 is an NS5A inhibitor being developed as an orally administered anti-HCV therapeutic. |
| Simeprevir | DRUG | Simeprevir is an orally active, small molecule inhibitor of the NS3/4A protease of HCV and indicated for the treatment of chronic HCV infection as a component of a combination antiviral treatment regimen. |
Inclusion Criteria: 1. Participant has provided written consent 2. In the Investigator's opinion, the participant is able to understand and comply with protocol requirements, instructions, and protocol stated restrictions and is likely to complete the study as planned 3. Male or female, 18-70 years...
AL-335 is an investigational small molecule being developed for the treatment of chronic hepatitis C, a viral infection of the liver. It has been studied in Phase 2 and Phase 1 clinical trials, including combinations with other direct-acting antivirals such as odalasvir and simeprevir. It is not approved for any use.
AL-335 is being developed by Vertex Pharmaceuticals Incorporated, which trades on the Nasdaq under the ticker VRTX. Vertex is the sponsor of the clinical program evaluating AL-335 in chronic hepatitis C.
AL-335 is in Phase 2 clinical development for chronic hepatitis C. Three trials have been completed, including one Phase 2 study and two Phase 1 studies, with a total enrollment of 305 participants. No trials are currently active, and the drug remains investigational.
AL-335 has been evaluated in three completed trials: NCT02569710, a Phase 2 study of AL-335 combined with odalasvir and simeprevir in 161 patients with chronic hepatitis C; NCT02512562, a Phase 1 drug interaction study in 32 healthy volunteers; and NCT02339207, a first-in-human Phase 1 study in 112 participants.
No, AL-335 is not FDA approved. It is an investigational small molecule that has completed Phase 2 and Phase 1 clinical trials for chronic hepatitis C. Approval status has not been granted, and further clinical development would be required before any regulatory submission.