Clinical Trials

Date: 2016-03-06

Type of information: Presentation of results at a congress

phase: 2b

Announcement: presentation of results at the 2016 AAAAI meeting in Los Angeles, California

Company: DBV Technologies (France)

Product: Viaskin® Peanut

Action mechanism:

• immunotherapy product. Viaskin® is an electrostatic patch, based on Epicutaneous Immunotherapy, or EPIT®, which administers an allergen directly onto the superficial layers of the skin to activate the immune system by specifically targeting antigen-presenting cells without allowing passage of the antigen into the bloodstream. Viaskin® Peanut is currently being investigated in clinical trials for treatment of peanut allergy.

Disease: peanut allergy

Therapeutic area: Allergic diseases - Immunological diseases

Country: Canada, France, The Netherlands, USA

Trial details:

• OLFUS-VIPES is an extension study for subjects who previously were randomized and have completed the VIPES study. It is planned to include 21 sites in 4 countries. Up to a maximum of 218 subjects can enroll in the OLFUS-VIPES study from the VIPES study. Subjects enrolled in this follow-up study will receive an additional 24 months of Viaskin® Peanut treatment followed by a 2 months period without treatment in order to assess the level of sustained tolerance. This study will address the crucial question of tolerance post treatment. OLFUS-VIPES is a multicenter study conducted in Europe and in North America.
• Subjects entering the OLFUS-VIPES study who had previously received Viaskin® Peanut at any of the three doses in the VIPES study will continue at the same dose (i.e., 50 µg or 100 µg or 250 µg of peanut protein). Subjects entering the OLFUSVIPES study who had previously received placebo in the VIPES study will be re-randomized in a 1:1:1 ratio to receive Viaskin® Peanut. The transition from the VIPES to the OLFUS-VIPES study will be blinded to investigators.
• Repeated daily application of Viaskin® Peanut will continue as in the VIPES study. A new patch will be applied every 24 hours on the inner side of both upper arms for adults (18 years or older) and adolescents (12-17 years), or on the inter-scapular area of the back for children (7-11 years).
• The objectives of this 24-month long-term efficacy and safety of the Viaskin® Peanut are as follows:
• - To assess the efficacy of Viaskin® Peanut up to 36 months of Epicutaneous Immunotherapy (EPIT) in peanutallergic subjects.
• - To evaluate the safety of long-term treatment with Viaskin® Peanut.
• - To evaluate the sustained tolerance to peanut after specific immunotherapy using Viaskin® Peanut.
• The Principal Coordinating Investigator for North America is Hugh Sampson, M.D., Professor of Pediatrics and Director of The Jaffe Food Allergy Institute at Mount Sinai School of Medicine. In Europe, the Principal Coordinator is Christophe Dupont, M.D, Ph.D., Necker Sick Children's Hospital, Paris, France.
• OLFUS enrolled 171 subjects who had previously received either placebo or one of three 12-month dose regimens administered during VIPES. During the first year of OLFUS, patients were to receive a daily application of Viaskin® Peanut 50 µg or Viaskin® Peanut 100 µg or Viaskin® Peanut 250 µg for 12 months. According to a study protocol change implemented in March 2014, all patients were switched to receive Viaskin® Peanut 250 ?g during OLFUS. Baseline response levels in OLFUS were based on the results of the last double-blind, placebo controlled food challenge (DBPCFC) in VIPES, and adjusted by the number of patients enrolling in OLFUS. As in VIPES, a responder in the OLFUS trial was defined as a subject who could reach a peanut protein eliciting dose equal to or greater than 1,000 mg peanut protein during the 12-month DBPCFC or a subject with a ?10-fold increase of the eliciting dose compared to the initial eliciting dose after 12 months of treatment. Patients enrolled in OLFUS who received placebo in VIPES were analyzed separately from subjects who initially received Viaskin® Peanut. (NCT01955109)

Latest news:

• • On February 10, 2017,  DBV Technologies announced that eight abstracts, seven of which will highlight data from the company’s Viaskin technology platform, were accepted for oral and poster presentation at the 2017 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in Atlanta, Georgia, March 3-6, 2017. Detailed results from the OLFUS-VIPES trial, which followed patients for a total of 36 months, will be presented.
• • On October 24, 2016, DBV Technologies announced topline results from the two-year OLFUS-VIPES study supporting the durable effect and favorable safety profile of Viaskin Peanut for the treatment of peanut-allergic children. Investigators in OLFUS followed patients who completed the VIPES study for an additional 24 months in order to assess the long-term safety and efficacy of Viaskin Peanut beyond the VIPES primary endpoint at 12 months. As in VIPES, participants’ response to treatment was evaluated by a double-blind, placebo-controlled food challenge (DBPCFC), which was administered at month-12 and month-24 during the OLFUS study. Consistent with prior observations in OLFUS, the favorable safety, tolerability and compliance profile of Viaskin Peanut was maintained from year-1 to year-2, with no treatment-related epinephrine use or serious adverse events (SAEs) reported in any of the subgroups. Patient compliance, which measures adherence to treatment dosing, was maintained at a median rate of 95.5%
• Highlights from the two-year follow-up results in children: Children treated with Viaskin Peanut 250 ?g throughout the duration of VIPES and OLFUS were observed to maintain long-lasting desensitization to peanut for a total of 36 months. Observations in these patients include the following: - Treatment benefit was observed to be long-lasting, with 83% (15/18) of children continuing to respond to treatment during the second year of OLFUS. - By month-24, a significant proportion of children were tolerating larger doses of peanut compared to the OLFUS baseline. - Mean and median cumulative reactive dose (CRD) of peanut protein, which measures threshold reactivity during the DBPCFC, progressed to 2,454 mg and 1,440 mg, respectively, at the completion of OLFUS; from 1,884 mg and 1,440 mg, respectively, during the month-12 interim assessment; and from 1,068 mg and 444 mg, respectively, at the OLFUS baseline. - Several children reached a CRD of at least 5,040 mg of peanut protein at the completion of the study (7/18 patients). - Peanut-specific immunoglobulin E (IgE) levels were maintained below baseline from year-1 to year-2, and immunoglobulin G4 (IgG4) levels remained high. After two years, 14% (3/21) of patients in this cohort discontinued treatment, none reportedly related to Viaskin Peanut.
• Despite treatment with suboptimal dose regimens, children treated with Viaskin Peanut 50 ?g or 100 ?g in VIPES, who later received the 250 ?g dose during OLFUS, showed increased levels of desensitization at month-24. Additional exploratory observations include the following: A majority of children receiving suboptimal dose regimens responded to treatment by the completion of OLFUS. Patients generally increased oral peanut intake over time in a dose-dependent manner. Patients initially treated with the lowest dose were more likely to discontinue therapy and were also less likely to achieve the highest CRD levels at month-24. Preliminary analysis on sustained benefit following treatment discontinuation: All subjects who were unresponsive to a cumulative reactive dose of above 1,440 mg of peanut protein at the month-24 DBPCFC in OLFUS were eligible to continue the study for two additional months. During this period, patients did not receive treatment and were required to maintain a peanut-free diet. In an exploratory analysis, all of the 19 children who completed the DBPCFC at month-26 reached a CRD of at least 1,440 mg, showing a meaningful durability of response in the absence of treatment.
• Complete results from the OLFUS study will be submitted for presentation at a future medical meeting.
• • On March 6, 2016,  DBV Technologies announced that results from the OLFUS trial were presented at the 2016 AAAAI meeting in Los Angeles, California. Dr. Hugh Sampson, Principal Investigator of the study, presented data that continued to support the favorable safety, efficacy and tolerability of Viaskin Peanut in peanut allergic patients. Clinical trial results continued to support the safety and tolerability profile of Viaskin® Peanut. There were no treatment-related serious adverse events observed during the trial nor use of epinephrine associated with treatment. No trial participant drop-outs due to drug-related adverse events were reported. The majority of adverse events were mild and moderate, consisting primarily of application site symptoms, with frequency decreasing over time. Additionally, high treatment adherence was also observed – a compliance rate of more than 96% across all cohorts was reported. Dr. Sampson also showed during his presentation that 80% of children ages six to 11 years responded to Viaskin Peanut 250 µg in the trial. After 24 months, the average cumulative reactive dose in this treatment group was 1,883 mg (1,440 mg median) peanut protein compared to 84 mg (44 mg median) at baseline. A doubling in response rates at 1,000 mg or more during the oral food challenge was observed during the second year of treatment in children dosed with Viaskin Peanut 250 µg, which increased to 60%. For reference, one peanut contains approximately 250 mg of peanut protein. Dr. Sampson concluded that Viaskin® Peanut continued to demonstrate a favorable safety profile along with an observed increase in treatment response over time. The open-label extension included 171 subjects from the VIPES Phase IIb clinical trial, who transitioned to the 250 µg dose of Viaskin® Peanut during OLFUS-VIPES. Viaskin was also observed to maintain response rates in adolescents and adults over time. Based on these results, DBV intends to explore additional Viaskin Peanut dose regimens in populations not included in the ongoing Phase III trial, which is studying Viaskin Peanut in children four to 11 years of age.
• • On October 5, 5015, DBV Technologies announced that topline findings from the first 12 months of the OLFUS study, support the long-term safety and efficacy of Viaskin® Peanut for the treatment of peanut allergy. During the first 12 months of OLFUS, no drug-related epinephrine use or serious adverse events due to Viaskin® Peanut were reported. The study’s median compliance rate, which was maintained at 96%, was also consistent with previously reported results. A preliminary analysis of the OLFUS data showed that 12 additional months of therapy with Viaskin® Peanut 250 ?g increased the number of patients benefiting from treatment to 70% in OLFUS from 50% in VIPES, with 80% of children (ages 6-11 at entry in VIPES) responding to therapy after 24 months. Patients who received placebo for one year in VIPES and received Viaskin® Peanut for 12 months in OLFUS showed a 50% response rate, which was consistent with findings from VIPES.
• Children treated for 24 months with Viaskin®Peanut 250 ?g: Both treatment benefit and consumption of peanut protein significantly increased with an additional 12 months of therapy. Out of the 28 children treated for 12 months with Viaskin® Peanut 250 µg in VIPES, 21 enrolled in OLFUS. One patient was lost to follow-up, but no other discontinuations were reported. In this subgroup, 80.0% of patients responded to treatment compared to 57.1% at the OLFUS baseline, consuming a 1,884 mg mean cumulative reactive dose (CRD) of peanut protein compared to a mean of 1,068 mg at the OLFUS trial initiation.  Serological markers in OLFUS showed the strengthening of the immunological changes initially observed in VIPES. After 24 months, a median 40% decrease from the VIPES baseline value in peanut-specific immunoglobulin E (IgE) was observed, while the high median levels in immunoglobulin G4 (IgG4) were maintained at an 800% increase from the VIPES baseline.
• Placebo-treated children in VIPES treated for 12 months with Viaskin®Peanut: New data from children treated for 12 months with Viaskin® Peanut were consistent with the previously reported safety and efficacy results observed in this patient population. Out of the 31 children who received placebo for 12 months in VIPES, 29 enrolled in OLFUS. One patient was unwilling to continue with treatment, but no other discontinuations were reported. A 53.6% response rate after 12 months of treatment with Viaskin® Peanut was observed compared to 17.2% at the OLFUS baseline. Patients consumed a mean CRD of 722 mg of peanut protein compared to 190 mg at the OLFUS baseline. The evolution of serological markers for patients treated with Viaskin® Peanut for 12 months was also consistent with data previously reported from VIPES.
• Adolescents and adults treated for 12 and 24 months with Viaskin®Peanut 250 ?g: For adolescent and adult patients treated for 24 months, no additional significant clinical response was observed relative to the OLFUS baseline. A response rate consistent with results observed in VIPES was shown in treatment-naïve adolescents and adults who received 12 months of therapy during OLFUS. These results confirm the company’s intention to explore a higher Viaskin® Peanut dosing regimen in this patient population.
• • On September 4, 2013, DBV Technologies has announced that the first patient has been enrolled in the open-label followup study (OLFUS) of VIPES phase IIb study to evaluate long-term efficacy and safety of Viaskin® Peanut.

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