Long-term Safety and Efficacy Outcome Study Comparing Children Previously Enrolled in Study ROPP-2008-01 for the Prevention of Retinopathy of Prematurity (ROP)

NCT02386839 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: SHP607-2012014-003556-31
• Study Type: interventional
• Target: 76
• Locations: 6 countries
• Sites: 16

Brief Summary

The main purpose of this study is to evaluate the long-term efficacy and safety outcomes following short-term exposure to rhIGF-1/rhIGFBP-3 versus standard neonatal care in Study ROPP-2008-01 (NCT01096784).

Conditions

Retinopathy of Prematurity (ROP)

Outcome Measures

Primary Outcomes (18)

• Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 6 Months Corrected Age (CA)

  Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.

  At 6 Months CA

• Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 12 Months CA

  Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.

  At 12 Months CA

• Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 20 Months CA

  Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.

  At 20 Months CA

• Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 24 Months CA

  Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.

  At 24 Months CA

• Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 4.75 Years CA

  Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.

  At 4.75 Years CA

• Number of Participants With Visual Acuity as Assessed by an Age-appropriate Method at 5 Years CA

  Standard age-appropriate methods were used to assess visual acuity (how well a participant sees at different distances) with teller acuity cards, LEA symbols test and Charts. It was categorized as following: normal (measurable acuity \>= 20/40 or \>= 15 cycles/degree); below normal (20/200 \<= measurable acuity \< 20/40 or 3 cycles/degree \<= measurable acuity \< 15 cycles/degree); poor (measurable acuity \<= 20/200 or \<= 3 cycles/degree). Corrected Age (weeks) was defined as Chronological Age (weeks) - 40 + Gestational Age (weeks) in this study.

  At 5 Years CA

• Number of Participants With Oculomotor Examination (Motility) and Ocular Alignment (Assessed by Corneal Light Reflex and Cover Test) at 12 Months CA

  Ocular alignment was assessed in primary gaze by comparing the position of the corneal light reflection in left eye and right eye (corneal light reflection assessment). Presence or absence of strabismus was recorded in primary gaze and in as many of the 9 positions of gaze as feasible with the cover test assessment of refixation movement. Extraocular muscle over action or deficiency was recorded. Ocular motility referred to eye movements governed by the 6 extraocular muscles in each eye. It was assessed by examiner observation of the participants ability to abduct, adduct, supra, and inferoduct each eye. Ocular alignment and motility included the presence or absence of strabismus (classified as Esotropia \[inward turn of the eye\], Exotropia \[outward turn of the eye\], Hypertropia \[upward turn of the eye\], Hypotropia \[downward turn of the eye\]) was recorded. Number of participants with combined data for ocular alignment and oculomotor examination (motility) at 12 months CA were reported.

  At 12 Months CA

• Number of Participants With Oculomotor Examination (Motility) and Ocular Alignment (Assessed by Corneal Light Reflex and Cover Test) at 24 Months CA

  Ocular alignment was assessed in primary gaze by comparing the position of the corneal light reflection in left eye and right eye (corneal light reflection assessment). Presence or absence of strabismus was recorded in primary gaze and in as many of the 9 positions of gaze as feasible with the cover test assessment of refixation movement. Extraocular muscle over action or deficiency was recorded. Ocular motility referred to eye movements governed by the 6 extraocular muscles in each eye. It was assessed by examiner observation of the participants ability to abduct, adduct, supra, and inferoduct each eye. Ocular alignment and motility included the presence or absence of strabismus (classified as Esotropia, Exotropia, Hypertropia, Hypotropia) was recorded. Number of participants with combined data for ocular alignment and oculomotor examination (motility) assessed by corneal light reflex and by the cover test at 24 months CA were reported.

  At 24 Months CA

• Number of Participants With Oculomotor Examination (Motility) and Ocular Alignment (Assessed by Corneal Light Reflex and Cover Test) at 5-Years CA

  Ocular alignment was assessed in primary gaze by comparing the position of the corneal light reflection in left eye and right eye (corneal light reflection assessment). Presence or absence of strabismus was recorded in primary gaze and in as many of the 9 positions of gaze as feasible with the cover test assessment of refixation movement. Extraocular muscle over action or deficiency was recorded. Ocular motility referred to eye movements governed by the 6 extraocular muscles in each eye. It was assessed by examiner observation of the participants ability to abduct, adduct, supra, and inferoduct each eye. Ocular alignment and motility included the presence or absence of strabismus (classified as Esotropia, Exotropia, Hypertropia, Hypotropia) was recorded. Number of participants with combined data for ocular alignment and oculomotor examination (motility) assessed by corneal light reflex and by the cover test at 5-Years CA were reported.

  At 5 Years CA

• Number of Participants With Nystagmus at 12 Months CA

  Nystagmus was observed during the ocular alignment assessments. Presence and absence of nystagmus was reported at 12 Months CA.

  At 12 Months CA

• Number of Participants With Nystagmus at 24 Months CA

  Nystagmus was observed during the ocular alignment assessments. Presence and absence of nystagmus was reported at 24 Months CA.

  At 24 Months CA

• Number of Participants With Nystagmus at 5 Years CA

  Nystagmus was observed during the ocular alignment assessments. Presence and absence of nystagmus was reported at 5 Years CA.

  At 5 Years CA

• Refraction With Cycloplegia as Assessed by Retinoscopy at 6 Months CA

  Refraction was a measure of the lens power required for a focused image on the retina. Refraction with cycloplegia was measured and recorded in diopters for each eye individually (left eye and right eye). Refraction with cycloplegia performed as part of the corrective lens determination procedure included measurements of sphere, cylinder, axis, and prism for each individual eye (left eye and right eye). For sphere, the negative values are summarized as 'nearsighted', and the positive values (including sphere of 0.00) are summarized as 'farsighted'.

  At 6 Months CA

• Refraction With Cycloplegia as Assessed by Retinoscopy at 12 Month CA

  Refraction was a measure of the lens power required for a focused image on the retina. Refraction with cycloplegia was measured and recorded in diopters for each eye individually (left eye and right eye). Refraction with cycloplegia performed as part of the corrective lens determination procedure included measurements of sphere, cylinder, axis, and prism for each individual eye (left eye and right eye). For sphere, the negative values are summarized as 'nearsighted', and the positive values (including sphere of 0.00) are summarized as 'farsighted'.

  At 12 Months CA

• Refraction With Cycloplegia as Assessed by Retinoscopy at 20 Month CA

  Refraction was a measure of the lens power required for a focused image on the retina. Refraction with cycloplegia was measured and recorded in diopters for each eye individually (left eye and right eye). Refraction with cycloplegia performed as part of the corrective lens determination procedure included measurements of sphere, cylinder, axis, and prism for each individual eye (left eye and right eye). For sphere, the negative values are summarized as 'nearsighted', and the positive values (including sphere of 0.00) are summarized as 'farsighted'.

  At 20 Months CA

• Refraction With Cycloplegia as Assessed by Retinoscopy at 4.75 Years CA

  Refraction was a measure of the lens power required for a focused image on the retina. Refraction with cycloplegia was measured and recorded in diopters for each eye individually (left eye and right eye). Refraction with cycloplegia performed as part of the corrective lens determination procedure included measurements of sphere, cylinder, axis, and prism for each individual eye (left eye and right eye). For sphere, the negative values are summarized as 'nearsighted', and the positive values (including sphere of 0.00) are summarized as 'farsighted'.

  At 4.75 Years CA

• Number of Participants With Stereoacuity as Assessed With the Lang Stereotest At 5 Years CA

  Stereoacuity, a measure of depth perception, was assessed using the Lang Stereotest. Number of participants with presence and absence of stereopsis (the ability to perceive depth and 3-dimensional structure) was reported.

  At 5 Years CA

• Number of Participants With Adverse Events (AEs)

  An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.

  From start of study up to end of study (up to 6.5 years)

Secondary Outcomes (22)

• Change From Baseline in Body Weight Z-score

  Baseline, 6 Months CA, 12 Months CA, 24 Months CA and 5 Years CA

• Change From Baseline in Height Z-score

  Baseline, 6 Months CA, 12 Month CA, 24 Months CA and 5 Years CA

• Change From Baseline in Head Circumference Z-score

  Baseline, 6 Months CA, 12 Months CA and 24 Months CA

• Change From Baseline (12 Months CA) in Cognitive Development as Assessed by Bayley Scales of Infant and Toddler Development (BSID-III) Composite Scores at 24 Months CA

  Baseline (12 Months CA), 24 Months CA

• Cognitive Development as Assessed by Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) Full Scale at 5 Years CA

  At 5 Years CA

Study Arms (2)

Antecedent Standard of Care

EXPERIMENTAL

Participants who were treated with standard neonatal care in study ROPP-2008-01 (NCT01096784) were enrolled in this group for assessment of rhIGF-1/rhIGFBP-3 long-term efficacy and safety outcomes.

Drug: rhIGF-1/rhIGFBP-3

Antecedent rhIGF-1/rhIGFBP-3

EXPERIMENTAL

Participants who were treated with rhIGF-1/rhIGFBP-3 in study ROPP-2008-01 (NCT01096784) were enrolled in this group for assessment of rhIGF-1/rhIGFBP-3 long-term efficacy and safety outcomes.

Drug: rhIGF-1/rhIGFBP-3

Interventions

rhIGF-1/rhIGFBP-3 DRUG

Participants who received "rhIGF-1/rhIGFBP-3" in study ROPP-2008-01 (NCT01096784) will be enrolled to this study. No investigational product will be administered in this study.

Also known as: Mecasermin rinfabate

Antecedent Standard of Care; Antecedent rhIGF-1/rhIGFBP-3

Eligibility Criteria

• Age: 40 Weeks - 108 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant was randomized in Study ROPP-2008-01 Section D (NCT01096784).
• Participants parent or legally authorized representative(s) must provide written informed consent prior to performing any study-related activities. Study-related activities are any procedures that would not have been performed during normal management of the participant.

You may not qualify if:

• Any other condition or therapy that, in the Investigator's opinion, may pose a risk to the Participant or interfere with the participants ability to be compliant with this protocol or interfere with the interpretation of results.
• The participant or participants parent or legally authorized representative(s) is unable to comply with the protocol as determined by the Investigator.

Sponsors & Collaborators

• Shire: lead

Study Sites (16)

University of South Alabama Children's and Women's Hospital

Mobile, Alabama, 36604, United States

Location

Vidant Medical Center

Greenville, North Carolina, 27834, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53715, United States

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Istituto Giannina Gaslini-Istituto Pediatrico di Ricovero e

Genova, 16147, Italy

Location

University of Padua

Padua, 35128, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

VU Medical Center

Amsterdam, 1081 HZ, Netherlands

Location

Ginekologiczno-Położniczy Szpital Kliniczny Uniwersytetu Medycznego w Poznan

Poznan, 60-535, Poland

Location

Skanes Universitetssjukhus Lund

Lund, SE-22185, Sweden

Location

Karolinska Universitetssjukhuset Huddinge

Stockholm, 141 86, Sweden

Location

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

St Peter's Hospital

Chertsey, KT16 0PZ, United Kingdom

Location

Alder Hey Childrens Hospital

Liverpool, L8 7SS, United Kingdom

Location

UCL EGA Institute for Women's Health

London, WC1E 6AU, United Kingdom

Location

MeSH Terms

Conditions

Retinopathy of Prematurity

Interventions

Insulin-Like Growth Factor I

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Somatomedins; Insulin-Like Peptides; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Blood Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Study Director
• Organization: Shire (Note: This product was divested to Oak Hill Bio in 2022)

ClinicalTransparency@takeda.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: March 12, 2015
• Study Start: March 26, 2015
• Primary Completion: September 28, 2021
• Study Completion: September 28, 2021
• Last Updated: May 18, 2022
• Results First Posted: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); US (4); IT (4); GB (4); PL (1); SE (2)