Phase 2 Trial to Assess Osilodrostat as Treatment for Children with Cushing’s Disease

Phase 2 Trial to Assess Osilodrostat as Treatment for Children with Cushing’s Disease

Novartis is launching a Phase 2 trial to assess the safety and efficacy of its investigational therapy osilodrostat — an inhibitor of cortisol synthesis — in children with Cushing’s disease.

The Phase 2 trial (NCT03708900) is expected to enroll 12 pediatric patients, from 6 to 18 years, who are ineligible for surgical treatment, have had disease recurrence after surgery, or are awaiting surgery.

The trial was described recently during the Endocrine Society’s 2019 Annual Meeting in New Orleans, Louisiana, in the poster, “Rationale and Methods for a Phase II Trial Evaluating Osilodrostat in Pediatric Patients with Cushing’s Disease.”

Osilodrostat, formerly known as LCI699, is an oral treatment that inhibits an enzyme called 11-beta-hydroxylase, which is involved in cortisol production. Blocking the enzyme prevents excessive cortisol production, normalizing the hormone’s levels in the body and reducing Cushing’s disease symptoms.

It works in a similar manner as the commonly used therapy Metopirone (metyrapone), but with stronger inhibitory activity and better stability.

In the trial, patients will receive oral tablets of osilodrostat for 12 weeks. Then, those who benefited from the treatment will continue taking osilodrostat for an additional nine months.

Patients weighing less than 60 kg (132 lbs) will start the treatment with a daily dose of one mg of osilodrostat, and those weighing more will take one mg twice daily. The dose may be adjusted according to mean urinary free cortisol (mUFC) — a metabolic hallmark of Cushing’s disease.

During the first 12 weeks of treatment, researchers will assess osilodrostat’s levels in circulation, to determine its maximum and minimum levels in patients. Side effects, changes in mUFC levels during the 12-week treatment, and the number of patients achieving normal mUFC levels during this period will also be assessed.

Researchers will examine osilodrostat’s efficacy after one year of treatment.

“This Phase 2, multicenter, open-label, non-comparative study will be the first study of osilodrostat in pediatric patients with Cushing’s disease,” the researchers wrote. “The results of this study may allow further clinical development of osilodrostat in children with Cushing’s disease.”

Novartis is also investigating osilodrostat in adult patients with persistent or recurrent Cushing’s disease in the ongoing LINC-4 Phase 3 trial (NCT02697734). The study is currently recruiting participants across 45 clinical sites worldwide, and expects to enroll approximately 69 patients — more information is available here.

Participants will be randomized to receive osilodrostat or a placebo for 12 weeks, after which all patients will receive treatment with osilodrostat for a total of 48 weeks.

As in the pediatric trial, participants who benefit from treatment can choose to continue receiving the therapy for up to 100 weeks.

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