E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Medically attended respiratory syncytial virus infection |
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E.1.1.1 | Medical condition in easily understood language |
RSV infection requiring medical care |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10038717 |
E.1.2 | Term | Respiratory syncytial viral infections |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part A:
• To determine the PK of IM administration of REGN2222
Part B: Study sites in the EU will only participate in Part B of the trial
• To demonstrate the efficacy of REGN2222 in preventing medically attended respiratory syncytial virus (RSV) infections (subjects with either RSV-confirmed hospitalizations or outpatient lower respiratory tract infection [LRTI]) |
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E.2.2 | Secondary objectives of the trial |
Part A:
• To evaluate safety, tolerability, and immunogenicity of REGN2222 following IM administration
Part B:
• To evaluate safety and tolerability of REGN2222
• To demonstrate the efficacy of REGN2222 in reducing RSV confirmed hospitalizations, emergency room (ER), urgent care (UC), or paediatric clinic visits
• To assess monthly serum levels of different dosing regimens of REGN2222
• To assess immunogenicity of REGN2222
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
An optional substudy is to collect a cheek swab from subjects for DNA for future use for the purpose of discovery of predictive biomarkers.
The purpose of the genomic analyses is to identify genomic associations with disease prognosis/severity and long-term outcomes, or other clinical outcome measures. These data may be used or combined with data collected from other studies to identify genomic markers that may predict response and elucidate mechanisms of disease. Analyses may include sequence determination or single nucleotide polymorphism studies of candidate genes and surrounding genomic regions. Genome-wide studies, including (but not limited to) single nucleotide polymorphism analyses, genomic sequencing, and transcriptome sequencing may also be performed. If indicated, genomic analyses may also be performed to identify markers associated with toxicity. |
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E.3 | Principal inclusion criteria |
A subject must meet the following criteria to be eligible for inclusion in the study:
1. Preterm, otherwise healthy male or female infant who has a chronological age of ≤6 months of age at the time of the first dose (ie, infant must receive the first dose on or before the subject’s 6-month birthday)
2. Gestational age at birth is no more than 35 weeks, 6 days
3. Parent(s) or legal guardian(s) of the infant is able to understand the study requirements, willing to provide informed consent, and legally able to provide informed consent. |
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E.4 | Principal exclusion criteria |
An infant who meets any of the following criteria will be excluded from the study:
1. Eligible and recommended to receive palivizumab per AAP or other local guidelines, standard practice, or by their healthcare provider
2. Children in whom a single blood draw would exceed 1% of their estimated total blood volume
3. Diagnosis of CLD defined as requirement of supplemental oxygen for at least 28 days (cumulative) after birth
4. Known hemodynamically significant congenital heart disease
5. Known immunodeficiency, neuromuscular disease, or congenital abnormalities of the airway
6. Known renal or hepatic dysfunction
7. Serum creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), total bilirubin (unless the investigator has evidence that increased indirect bilirubin corresponds to a Gilbert’s-type syndrome) that is >1.1 times the upper limit of normal
8. Any other laboratory findings showing evidence of organ dysfunction or any clinically significant deviation from the normal range, as decided by the investigator at the screening visit
9. Use of any concomitant medications within 30 days of the screening visit, including prescription medications (except those used as standard of care, such as antibiotics, topical analgesic for blood draws [not to be used for IM injections, including vaccines], nutritional supplements, medications for gastroesophageal reflux, topical medications, and eye drops), and over-the-counter medications (except for vitamin supplements, ibuprofen, acetaminophen, or topical creams)
10. Vaccine or other IM drug administration within 2 days before or after dosing of the study drug
11. History of hospitalization prior to screening; exceptions include hospitalization for delivery and the subsequent stay for preterm infants.
12. Life expectancy of <6 months
13. Major congenital malformations, including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders
14. Known or suspected impairment of immunological functions or autoimmune diseases
15. History of anaphylaxis
16. History of a seizure disorder
17. Previously received palivizumab, IV gamma globulin, or any other investigational RSV prophylaxis or vaccine product
18. Previous allergic reaction to IV immunoglobulin, blood products or other foreign proteins, such as vaccines and monoclonal antibodies, or any of the components of the investigational product formulation
19. Participation in any clinical research study evaluating another investigational drug or therapy that is inconsistent with current standard of care within at least 5 half-lives (whichever is longer) of the investigational drug prior to the screening visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are the following:
Part A:
• Serum concentration of REGN2222 over time and other PK parameters
Part B:
• Proportion of subjects with a medically attended RSV infection (hospitalization or outpatient LRTI) during the study period. A medically attended RSV infection is defined as an infant with a positive RSV test by RT PCR with any of the following events:
- Hospitalized (on the basis of the assessment of the admitting physician) for RSV infection
- Outpatient visit (ER, UC, or paediatric clinic [for either a sick or well visit]) with RSV LRTI.
An RSV LRTI in an infant is defined as an RSV-proven respiratory infection (ie, positive RSV RT-PCR test) with parent(s)/legal guardian(s) report of cough or difficulty breathing, and with 1 of the following signs of LRTI, as assessed by a healthcare provider:
• Lower Chest wall indrawing
• Hypoxemia (peripheral capillary oxygen saturation <95% breathing room air)
• Wheezing or crackles
Only medically attended respiratory visits occurring during the first 150 day period will be counted toward the primary endpoint. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Collected between first dose to study Day 150 |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are the following:
Part A:
• Incidence and severity of TEAEs
• Presence and titer of anti-REGN2222 antibodies
Part B:
• Proportion of subjects who have RSV-confirmed hospitalization, ER,UC, or paediatric clinic visits (for upper or lower respiratory infection) during the study period
•PK parameters using sparse sampling
•Presence and titer of anti-REGN2222 antibodies
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Collected between first dose to study Day 150 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 76 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Bulgaria |
Canada |
Chile |
Denmark |
Finland |
Germany |
Hungary |
Netherlands |
New Zealand |
Panama |
South Africa |
Spain |
Sweden |
Turkey |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |