Clinical Trials

Date: 2017-11-06

Type of information: Results

phase: 3

Announcement: results

Company: advicenne

Product: ADV7103 (tripotassium citrate monohydrate and potassium hydrogen carbonate)

Action mechanism:

• ADV7103 combines two active pharmaceutical ingredients, tripotassium citrate monohydrate and potassium hydrogen carbonate. The product is currently being evaluated in a pivotal Phase III trial in Europe in children and adults to address distal Renal Tubulopathy Acidosis (dRTA), a disease that leads to an unbalanced pH in the body that causes various complications such as hearing loss, failure to thrive, rickets (a condition that affects bone development in children) and renal impairment, ultimately leading to renal failure. The European Commission granted orphan drug designation (ODD) to ADV7103 for the treatment of dRTA in June 2017.

Disease: distal renal tubular acidosis (dRTA)

Therapeutic area: Rare diseases

Country:

Trial details:

Latest news:

• • On November 6, 2017, Advicenne announced positive 6 months follow-up data from the pivotal phase III study (B22CS) assessing ADV7103 in adults and children suffering from distal renal tubular acidosis (dRTA).  The preliminary results of the 6-month follow up study assessed the safety and efficacy of twice daily dosing of ADV7103 for the treatment of dRTA in both adult and pediatric patients. The extension study (B22CS) followed the pivotal phase III trial (B21CS), which showed ADV7103’s ability to restore the main biological defects observed with the disease, meeting primary and secondary endpoints. The product’s efficacy, was shown to be maintained at 6 months in this open label extension study, with blood bicarbonate levels above 21 mM - the normal level - in 79% of the patients. Individual ADV7103 doses ranged from 1.3 to 7.2 mEq/kg/day.
• Overall, patients and/or their parents were extremely satisfied with ADV7103. This was measured using a visual analogue scale (VAS) questionnaire quoting from 0 (no improvement at all) to 100% (extremely important improvement). The change of treatment from standard of care to ADV7103 allowed an average improvement of the patients’ quality of life of 80.5%; depending on the age group considered the improvement ranged from 76 to 98%. Positive Phase III results for ADV7103 were announced in September this year and demonstrated ADV7103’s ability to normalise the main biological defects observed with the disease. The poster entitled “Safety and efficacy of ADV7103, an innovative prolonged-release oral alkalising combination product, after 6-months treatment in distal renal tubular acidosis (dRTA) patients" was presented at ASN on 2nd November 2017.
• • On September 17, 2017, Advicenne announced top-line data from a pivotal phase III study assessing ADV7103 in adults and children suffering from distal Renal Tubular Acidosis (dRTA). The objective of the study was to evaluate the efficacy, safety and acceptability of ADV7103. The productis given twice a day in contrast to the current standard of care (SoC), which are usually various unapproved products administered every four to six hours to attempt to re-balance the body’s pH and to normalise blood potassium level (kalaemia).
• The Phase III study of ADV7103 was shown to restore the main biological defects observed with the disease meeting positively primary and secondary endpoints. Normal blood bicarbonate levels were attained in most patients treated with doses of ADV7103 ranging from 0.75 to 8.45 mEq/kg/day. Mean doses of 1.7, 2.3, 3.8 and 6.1 mEq/kg/day ADV7103 were given, respectively, in adults, adolescents, children, and infants. Non-inferiority of ADV7103 vs. SoC or baseline literature data was consistently demonstrated (per protocol, intention-to-treat, as well as sensitivity analyses). Kalaemia was normalised with ADV7103 with only two doses per day. These analyses were able to show that ADV7103 is superior to the SoC (p<0.0047).
• Further important advantages of ADV7103 which were demonstrated in the study were its good palatability, ease of administration and gastrointestinal tolerability. The data from this pivotal phase III study was presented at the 50th European Society of Paediatric Nephrology (ESPN) 2017 Annual Meeting which was held from the 7th to 9th of September in Glasgow, UK, during an oral communication on Saturday, 9th September.
• • On June 21, 2017, Advicenne announced that the company will present preliminary Phase III clinical data on ADV7103 in an oral presentation at the 50th European Society of Paediatric Nephrology (ESPN) 2017 Annual Meeting. (“Efficacy and acceptability of ADV7103, an innovative prolonged-release oral alkalising formulation in distal Renal Tubular Acidosis (dRTA) patients” - Preliminary Phase III Results - Presenting author: Aurelia Bertholet-Thomas, M.D., Centre de Référence des Maladies Rénales Rares, Bron, France).

Is general: Yes