Clinical Trials

Date: 2016-02-24

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the Conference on Retroviruses and Opportunistic Infections (CROI) in Boston

Company: ViiV Healthcare (UK - USA)

Product: cabotegravir

Action mechanism:

• integrase strand transfer inhibitor. Cabotegravir is an investigational integrase strand transfer inhibitor (INSTI) and analogue of dolutegravir (Tivicay®). The drug is being developed by ViiV Healthcare for the treatment and prevention of HIV and is currently being evaluated as a once-daily oral tablet formulation and as a long-acting nanosuspension formulation for intramuscular (IM) injection.

Disease: HIV prevention

Therapeutic area: Infectious diseases

Country:

Trial details:

• ECLAIR (Phase IIa Study to Evaluate the Safety, Tolerability and Acceptability of Long Acting Injections of the HIV Integrase Inhibitor [cabotegravir] in HIV Uninfected Men) is a double-blind, randomised, multi-centre US study in HIV-uninfected healthy adult males not at high risk of acquiring HIV. It evaluated cabotegravir long-acting injections as a candidate for HIV Pre-Exposure Prophylaxis (PrEP).

Latest news:

• • On 24 February 2016, ViiV Healthcare presented positive results from the 41 week phase IIa ECLAIR study, which evaluated the safety, tolerability, dosing and satisfaction with cabotegravir as monotherapy for pre-exposure prophylaxis (PrEP) in HIV-uninfected healthy adult males not at high risk of acquiring HIV. Results were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in Boston. Data from the study support the advancement of cabotegravir, an integrase strand transfer inhibitor, to the next stage of development as a potential drug for HIV prevention. Adverse events (AEs) during the injection phase occurred in 98% and 90% of cabotegravir and placebo group participants, respectively.1Injection site pain was the most frequently reported Grade 2-4 AE for those receiving cabotegravir (59%, compared to 5% for placebo).1
• The ECLAIR study randomised 127 HIV-uninfected participants to cabotegravir or placebo (5:1) beginning with a safety assessment on oral cabotegravir (30mg) or matching placebo tablet for four weeks, followed by intramuscular injections of 800mg cabotegravir or placebo (sterile saline solution) dosed once every 12 weeks for three cycles.A majority of participants in the study reported satisfaction with cabotegravir injections. Following repeat injections, 67/91 (74%) of participants favoured cabotegravir long-acting injections compared to oral cabotegravir. The ECLAIR study also collected cabotegravir exposure data throughout each 12-week dosing interval. Results showed drug concentrations were lower than anticipated at the end of the dosing interval in approximately two-thirds of participants.1 As a result, an alternative dosing strategy of 600mg intramuscular injections every eight weeks is now under investigation as a means to optimise cabotegravir dosing prior to future safety and efficacy studies.
• Adverse events (AEs) leading to withdrawal during the oral phase (7/105) included three events of neutropenia, three events of increasing blood creatine phosphokinase (CPK) and one event of fatigue.1 For participants who entered the injection phase, a similar proportion (93% [87/94] for cabotegravir and 95% [20/21] for placebo) completed all three injection cycles.1 Self- reported injection intolerability led to withdrawal in 4% (4/94) of cabotegravir participants.1 One participant in the placebo group withdrew during the injection phase due to HIV seroconversion.1
• The number of Grade 2-4 AEs on the cabotegravir arm was higher compared to placebo during the injection phase (80% [75/94] for cabotegravir vs 48% [10/21] for placebo).1Grade 2 AEs in the injection phase not related to injection site pain included pyrexia (fever) (7% [7/94] for cabotegravir subjects and 0% for placebo subjects), injection site pruritus (itching) (6% [6/94] for cabotegravir subjects and 0% for placebo subjects) and injection site swelling (6% [6/94] for cabotegravir subjects and 0% for placebo subjects).

   

Is general: Yes