Clinical Trials

Date: 2016-06-30

Type of information: Results

phase: 2

Announcement: results

Company: Shire (UK - USA)

Product: SHP607

Action mechanism:

• protein. SHP607 is a recombinant human biologic protein complex of insulin-like growth factor-1 (IGF-1) and its principal binding protein, IGF binding protein 3 (IGFBP3) [rhIGF-1/rhIGFBP-3]. In clinical trials, this replacement protein complex was provided to extremely preterm infants through intravenous infusion, beginning within the first 24 hours of life and delivered continuously until endogenous production of IGF-1 begins naturally at approximately 30 weeks postmenstrual age.

Disease: retinopathy of prematurity

Therapeutic area: Rare diseases

Country: Italy, Netherlands, Poland, Sweden, UK, USA

Trial details:

• The Phase 2 study (ROPP-2008-01) was a multicenter, randomized, controlled study that compared SHP607 to standard neonatal care in 121 premature infants born at a gestational age of between 23 weeks and 27 weeks+6 days. Infants randomized to active treatment received a standardized dosage of 250 µg/kg per day as a continuous 24-hour infusion from the day of birth (Day 0) through postmenstrual age (defined as gestational age plus time elapsed from birth) of 29 weeks + 6 days, at which point the infant’s body would begin producing enough IGF-1 to maintain sufficient levels in the blood. The target drug exposure was defined as at least 70% of measured IGF-1 levels within the normal intrauterine range and at least 70% of the intended duration of therapy based on gestational age. After the short-term treatment phase, all participants were followed to a postmenstrual age of 40 weeks ± 4 days. (NCT01096784)

Latest news:

• • On June 30, 2016, Shire announced that its Phase 2 study evaluating an investigational protein replacement, SHP607, did not meet its primary endpoint of reducing the severity of retinopathy of prematurity (ROP), a rare eye condition. The study, however, demonstrated clinically relevant effects in secondary endpoints related to the development of severe bronchopulmonary dysplasia (BPD), a chronic lung disease, and severe intraventricular hemorrhage (IVH), a type of brain injury, both of which have lifelong negative implications for normal development.
• The Phase 2 study included 121 extremely premature infants (born between 23 weeks and 27 weeks +6 days) randomized at birth to either SHP607 or standard neonatal care, and treated continuously until an equivalent gestational age of 30 weeks. IGF-1 is a growth factor that plays a major role in the development of the growing fetus in the uterus. It is supplied by the mother until about 30 weeks of gestation when the fetus begins producing the growth factor on its own. Levels of IGF-1 dramatically decrease in infants born extremely premature (before 28 weeks of gestation), thereby increasing the risk for complications related to the lungs, brain, eyes, and other organs.
• The Phase 2 top-line data showed a 53% reduction in the incidence of severe BPD, as defined by oxygen challenge testing, in all assessed patients that received SHP607, as compared to untreated infants; and an 89% reduction in those who achieved the prespecified target drug exposure, based on serum concentrations of IGF-1, as compared to untreated infants. The data also showed a 44% reduction in the incidence of severe IVH (Grade III and IV on centrally read ultrasounds) in all assessed patients that received SHP607, as compared to untreated infants; and a 64% reduction in those who achieved the prespecified target drug exposure based on serum concentrations of IGF-1, as compared to untreated infants. The secondary endpoint of time to discharge from neonatal intensive care was not met.
• Research suggests that 60% of extremely premature infants experience one or more severe complications related to prematurity, which include: IVH (grade ?3); BPD; or ROP. Severe complications can have life-long implications for the developing infant. Later this year, Shire expects to begin discussions with regulatory authorities about a phase 3 clinical program focusing on clinically relevant complications of prematurity. Shire is enrolling patients from the Phase 2 study into a five-year observational long-term outcomes study.

     

Is general: Yes