Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Coversin, rEV576
rVA576 · 4 trials · 3 indications
Haemoglobin stabilisation rate defined as haemoglobin greater than the set point for each patient during the pre-study randomisation period and the avoidance of PRBC transfusions during the treatment period.
Proportion of participants reporting grade 3, 4 and 5 adverse events, which are related/possibly related to rVA576 during the treatment period. Treatment emergent adverse events (TEAEs) consist of: * Change from baseline in physical examination * ECG * Clinical laboratory tests * Vital signs The Common Terminology Criteria for Adverse Events (CTCAE v4.03) will be used to grade adverse events.
Measurement of serum lactate dehydrogenase (LDH)
LDH is an indicator of disease progression in patients with PNH and is expected to fall to within 2x upper limit of normal (ULN) within 28 days in successfully treated patients. Units are measured in ratio of LDH:ULN, where the ULN is 250 U/L. The primary efficacy endpoint was the LDH AUC from Day 0 to 28 compared with 28 days pretreatment. Data for the 28 days pre-treatment was not collected, and as only one patient was recruited, the LDH values compared with baseline and the ratio of LDH to the Upper Limit of Normal (ULN) are presented.
The number and type of reported AEs will be recorded as well as the opinion of the Principle Investigator (PI) as to their possible relationship to the study drug.
| Arm | Type | Description |
|---|---|---|
| Arm 1 - 9 months of treatment (rVA576 plus SOC) | EXPERIMENTAL | 6 months (SOC plus rVA576), Followed by a further 3 months of (SOC plus rVA576). |
| Arm 2 - 6 months on SOC | EXPERIMENTAL | 6 months on SOC only. Followed by 3 months (SOC plus rVA576). |
| Open-label single arm study | EXPERIMENTAL | - |
| Coversin treatment | EXPERIMENTAL | Coversin - 22.5mg followed by 45mg for 6 months. |
| Coversin (Nomacopan) | OTHER | This is an open label, non-comparator study. Patient will be given a single ablating dose of 0.57mg/kg per subject followed by daily repeat maintenance doses. The initial repeat dose will be 25% of the ablating dose. If this is insufficient to maintain complement inhibition at ≤10% of baseline (pre-treatment) level after 5 days of treatment the daily dose will be increased by doubling until that level of inhibition is achieved. In the event of 100% inhibition being achieved the dose may be titrated downwards at the PI's discretion until a satisfactory clinical result is obtained. If at any point in treatment complement inhibition falls to less than 50% of baseline a further ablating dose of 0.57mg/kg should be given. Coversin lyophilised powder in each vial was diluted with 0.6 mL water for injection prior to use. |
| Name | Type | Description |
|---|---|---|
| rVA576 | DRUG | 6 months of treatment, rVA576 plus SOC. Followed by a further 3 months of rVA576 plus SOC. In total, 9 months on rVA576 plus SOC. |
| Standard of care (SOC) | OTHER | 6 months on SOC followed by 3 months of treatment with rVA576 plus SOC. In total, 3 months on rVA576 plus SOC. |
| Coversin | DRUG | Coversin - 22.5mg followed by 45mg for 6 months. |
Inclusion Criteria: 1. Willing to give informed consent to treatment with rVA576 2. Diagnosed with paroxysmal nocturnal haemoglobinuria (PNH) 3. Have not received any complement inhibitor within the 4 months prior to screening 4. ≥ 18 years of age at the time of screening 5. Weight ≥50kg 6. Complet...
rVA576 is an investigational small molecule complement inhibitor being developed by Akari Therapeutics Plc. It is designed to target the complement protein C5 and is being studied in bullous pemphigoid and paroxysmal nocturnal hemoglobinuria. It has completed Phase 2 and Phase 3 clinical trials but is not approved for commercial use.
rVA576 is being studied for the treatment of adult patients with mild to moderate bullous pemphigoid, a rare autoimmune skin blistering disease. A completed Phase 2 trial evaluated rVA576 in this indication. The drug is investigational and has not been approved for any use.
rVA576 targets complement protein C5, a key component of the complement system. By binding to C5, rVA576 is designed to inhibit the complement cascade, which is implicated in conditions such as bullous pemphigoid and paroxysmal nocturnal hemoglobinuria.
rVA576 is being developed by Akari Therapeutics Plc, a biopharmaceutical company traded on the Nasdaq under the ticker AKTX. Akari Therapeutics is focused on developing therapies for autoimmune and inflammatory diseases.
rVA576 has completed a Phase 2 trial in bullous pemphigoid and a Phase 3 trial in paroxysmal nocturnal hemoglobinuria. It is an investigational drug and has not been approved by the FDA or any regulatory agency for commercial use.
rVA576 has been evaluated in two completed clinical trials: NCT04035733, a Phase 2 study in adult mild to moderate bullous pemphigoid conducted in Germany and the Netherlands, and NCT03588026, a Phase 3 study in paroxysmal nocturnal hemoglobinuria conducted in Kazakhstan, Lithuania, and Sri Lanka. Both trials are completed.