The Mike McMorris Cystic Fibrosis Research and Care Center, part of the Children’s Hospital Colorado, is one of the 82 clinical sites involved in the Phase 3 clinical trial that is assessing the efficacy of VX-659 in a triple combination with Symdeko (tezacaftor/ivacaftor and ivacaftor).
The trial (NCT03447249) will test the triple combination in cystic fibrosis (CF) patients with one F508del mutation and one minimal function mutation in the CFTR gene (the gene that is defective in CF patients).
Currently recruiting participants, Vertex Pharmaceuticals‘ study plan to enroll about 360 CF patients, ages 12 or older, across clinical sites in the United States, Canada, Europe, and Israel.
Data collected from this trial is expected to support a request to approve the treatment regimen made to the U.S. Food and Drug Administration (FDA), and potentially regulatory agencies elsewhere. This would be an important step for this particular population of patients, as there are no CFTR modulators available for them.
“Different mutations cause different defects in the protein produced by the CFTR gene, and the medications that have been developed so far – such as Orkambi, Kalydeco and Symdeko – are effective only in people with specific mutations,” Edith Zemanick, MD, pediatric pulmonologist at Children’s Colorado, said in a press release.
“What is really exciting about these Phase 3 trials is the prospect of developing a combination therapy to treat people with a single F508del mutation. This would mean that more people than ever before could benefit from modulator therapies,” she added.
Trial participants will be randomized to receive the triple combo — 240 mg VX-659, 100 mg tezacaftor and 150 mg ivacaftor in the morning, and again the same dose of ivacaftor in the evening — or to a placebo for 24 weeks.
They then will have the possibility of continuing treatment with the combo therapy for up to 96 weeks in an open-label extension phase (NCT03447262).
The Phase 3 study is supported by positive data from a previous Phase 2 study (NCT03224351), which showed that the triple combination could significantly improve lung function and reduce the levels of sweat chloride in these patients.
The study’s announcement follows the recent approval of Symdeko as a treatment for patients ages 12 or older with two copies of the F508del mutation or one of 26 other specified CFTR mutations.
Children’s Colorado also participated in some of the Phase 3 trials of Symdeko, and is currently involved in the Phase 3 study (NCT03559062) of it in children ages 6 to 11. This new trial is also currently recruiting participants. For further information, please click on the study’s NCT number.
“We have been involved in CF clinical trials with Children’s Colorado since our son was little,” said Libby Colbert, the mother of 12-year-old patient at Children’s Colorado. “He started taking the drug [Symdeko] right after its approval by the FDA, and we saw a difference almost immediately. The combination of tezacaftor and ivacaftor has been a great medicine for Noah and has helped him smell and breathe better.”
“We are grateful to live close to a great hospital where Noah is receiving exceptional care and is among leaders in CF research. This is a great step for all those living with CF and we are excited for this milestone in medicine,” she added.