Protocol to Monitor the Neurological Development of Infants With Exposure in Utero From Birth to 15 Months in Tanezumab Clinical Studies

Study Overview
=================
Brief Summary
-----------------
A4091065 is a multicenter, prospective, cohort study with enhance physical an neurodevelopmental surveillance to characterize the outcomes related to the development of infants up to the age of 15 months who were potentially exposed to tanezumab, placebo or comparator via maternal exposure or in utero in any tanezumb study.

Detailed Description
-----------------
A4091065 is a long term observational follow up study of subjects from tanezumab interventional studies A4091056, A4091057, A4091058, A4091059, A4091061 or A4091063

Official Title
-----------------
A PROTOCOL TO MONITOR FROM BIRTH TO AGE 15 MONTHS THE NEUROLOGICAL DEVELOPMENT OF INFANTS WITH EXPOSURE IN-UTERO IN TANEZUMAB CLINICAL STUDIES AT ALL INVESTIGATIONAL SITES

Conditions
-----------------
Cancer Pain, Osteoarthritis, Recurrent Low Back Pain

Intervention / Treatment
-----------------
* Drug: Investigational medical product (IMP) administered in parent study


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is an infant born to a mother who was exposed to study drug on a tanezumab clinical study. The infant's mother (who was the tanezumab clinical study participant) must review, agree and sign an informed consent document explaining the details of the perinatal and post natal follow up. Where local regulations mandate, the male parent would also review and sign the informed consent. Parents or legal guardian must be willing and able to comply with scheduled visits and study procedures. Exclusion Criteria: There are no exclusion criteria for participating in this study.

Ages Eligible for Study
-----------------
Minimum Age: 0 Years
Maximum Age: 2 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1<br>Long term observational study of subjects from tanezumab parent study | Drug: Investigational medical product (IMP) administered in parent study<br>* IMP as administered in parent study. IMP would have been either placebo, tanezumab, celecoxib, naproxen, diclofenac, administered in parent study<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occipital-frontal Head Circumference During 0 to Less Than or Equal to (<=) 2 Months of Participant's Age | Occipital-frontal head circumference of participants in centimeter (cm) was reported. | Any visit during participants' age from 0 to 2 Months | 
| Occipital-frontal Head Circumference at 8 Months of Participant's Age | Occipital-frontal head circumference of participants in centimeter (cm) was reported. | At 8 Months of participants' age | 
| Occipital-frontal Head Circumference at 15 Months of Participant's Age | Occipital-frontal head circumference of participants in centimeter (cm) was reported. | At 15 Months of participants' age | 
| Occipital-frontal Head Circumference During 0 to Less Than or Equal to (<=) 3 Months of Participant's Age | Occipital-frontal head circumference of participants in centimeter (cm) was reported. | Any visit during participants' age from 0 to 3 Months | 
| Occipital-frontal Head Circumference During Greater Than (>) 3 to <=6 Months of Participant's Age | Occipital-frontal head circumference of participants in cm was reported. | Any visit during participants' age above 3 Months and up to 6 Months | 
| Occipital-frontal Head Circumference During >6 to <=9 Months of Participant's Age | Occipital-frontal head circumference of participants in cm was reported. | Any visit during participants' age above 6 Months and up to 9 Months | 
| Occipital-frontal Head Circumference During >15 to <=18 Months of Participant's Age | Occipital-frontal head circumference of participants in cm was reported. | Any visit during participants' age above 15 Months and up to 18 Months | 
| Occipital-frontal Head Circumference During >21 to <=24 Months of Participant's Age | Occipital-frontal head circumference of participants in cm was reported. | Any visit during participants' age above 21 Months and up to 24 Months | 
| Occipital-frontal Head Circumference During >24 to <=30 Months of Participant's Age | Occipital-frontal head circumference of participants in cm was reported. | Any visit during participants' age above 24 Months and up to 30 Months | 
| Body Length During 0 to Less Than or Equal to (<=) 2 Months of Participant's Age | Body length of participants in cm was reported. | Any visit during participants' age from 0 to 2 Months | 
| Body Length at 8 Months of Participant's Age | Body length of participants in cm was reported. | At 8 Months of participant's age | 
| Body Length at 15 Months of Participant's Age | Body length of participants in cm was reported. | At 15 Months of participant's age | 
| Body Length During 0 to <=3 Months of Participant's Age | Body length of participants in cm was reported. | Any visit during participants' age from 0 to 3 Months | 
| Body Length During >3 to <=6 Months of Participant's Age | Body length of participants in cm was reported. | Any visit during participants' age above 3 Months and up to 6 Months | 
| Body Length During >6 to <=9 Months of Participant's Age | Body length of participants in cm was reported. | Any visit during participants' age above 6 Months and up to 9 Months | 
| Body Length During >15 to <=18 Months of Participant's Age | Body length of participants in cm was reported. | Any visit during participants' age above 15 Months and up to 18 Months | 
| Body Length During >21 to <=24 Months of Participant's Age | Body length of participants in cm was reported. | Any visit during participants' age above 21 Months and up to 24 Months | 
| Body Length During >24 to <=30 Months of Participant's Age | Body length of participants in cm was reported. | Any visit during participants' age above 24 Months and up to 30 Months | 
| Body Weight During 0 to Less Than or Equal to (<=) 2 Months of Participant's Age | Body weight of participants in kilogram (kg) was reported. | Any visit during participants' age from 0 to 2 Months | 
| Body Weight at 8 Months of Participant's Age | Body weight of participants in kilogram (kg) was reported. | At 8 Months of participants' age | 
| Body Weight at 15 Months of Participant's Age | Body weight of participants in kilogram (kg) was reported. | At 15 Months of participants' age | 
| Body Weight During 0 to <=3 Months of Participant's Age | Body weight of participants in kilogram (kg) was reported. | Any visit during participants' age from 0 to 3 Months | 
| Body Weight During >3 to <=6 Months of Participant's Age | Body weight of participants in kg was reported. | Any visit during participants' age above 3 Months and up to 6 Months | 
| Body Weight During >6 to <=9 Months of Participant's Age | Body weight of participants in kg was reported. | Any visit during participants' age above 6 Months and up to 9 Months | 
| Body Weight During >15 to <=18 Months of Participant's Age | Body weight of participants in kg was reported. | Any visit during participants' age above 15 Months and up to 18 Months | 
| Body Weight During >21 to <=24 Months of Participant's Age | Body weight of participants in kg was reported. | Any visit during participants' age above 21 Months and up to 24 Months | 
| Body Weight During >24 to <=30 Months of Participant's Age | Body weight of participants in kg was reported. | Any visit during participants' age above 24 Months up to 30 Months | 
| Systolic and Diastolic Blood Pressure During 0 to Less Than or Equal to (<=) 2 Months of Participant's Age | Systolic and diastolic blood pressure of participants in millimeter of mercury (mmHg) was reported. | Any visit during participants' age from 0 to 2 Months | 
| Systolic and Diastolic Blood Pressure at 8 Months of Participant's Age | Systolic and diastolic blood pressure of participants in millimeter of mercury (mmHg) was reported. | At 8 Months of participants' age | 
| Systolic and Diastolic Blood Pressure at 15 Months of Participant's Age | Systolic and diastolic blood pressure of participants in millimeter of mercury (mmHg) was reported. | At 15 Months participants' age | 
| Systolic and Diastolic Blood Pressure During 0 to <=3 Months of Participant's Age | Systolic and diastolic blood pressure of participants in millimeter of mercury (mmHg) was reported. | Any visit during participants' age from 0 to 3 Months | 
| Systolic and Diastolic Blood Pressure During >3 to <=6 Months of Participant's Age | Systolic and diastolic blood pressure of participants in mmHg was reported. | Any visit during participants' age above 3 Months and up to 6 Months | 
| Systolic and Diastolic Blood Pressure During >6 to <=9 Months of Participant's Age | Systolic and diastolic blood pressure of participants in mmHg was reported. | Any visit during participants' age above 6 Months and up to 9 Months | 
| Systolic and Diastolic Blood Pressure During >15 to <=18 Months of Participant's Age | Systolic and diastolic blood pressure of participants in mmHg was reported. | Any visit during participants' age above 15 Months and up to 18 Months | 
| Systolic and Diastolic Blood Pressure During >21 to <=24 Months of Participant's Age | Systolic and diastolic blood pressure of participants in mmHg was reported. | Any visit during participants' age above 21 Months and up to 24 Months | 
| Systolic and Diastolic Blood Pressure During >24 to <=30 Months of Participant's Age | Systolic and diastolic blood pressure of participants in mmHg was reported. | Any visit during participants' age above 24 Months and up to 30 Months | 
| Pulse Rate During 0 to Less Than or Equal to (<=) 2 Months of Participant's Age | Pulse rate of participants in beats per minute was reported. | Any visit during participants' age from 0 to 2 Months | 
| Pulse Rate at 8 Months of Participant's Age | Pulse rate of participants in beats per minute was reported. | At 8 Months of participants' age | 
| Pulse Rate at 15 Months of Participant's Age | Pulse rate of participants in beats per minute was reported. | At 15 Months of participants' age | 
| Pulse Rate During 0 to <=3 Months of Participant's Age | Pulse rate of participants in beats per minute was reported. | Any visit during participants' age from 0 to 3 Months | 
| Pulse Rate During >3 to <=6 Months of Participant's Age | Pulse rate of participants in beats per minute was reported. | Any visit during participants' age above 3 Months and up to 6 Months | 
| Pulse Rate During >6 to <=9 Months of Participant's Age | Pulse rate of participants in beats per minute was reported. | Any visit during participants' age above 6 Months and up to 9 Months | 
| Pulse Rate During >15 to <=18 Months of Participant's Age | Pulse rate of participants in beats per minute was reported. | Any visit during participants' age above 15 Months and up to 18 Months | 
| Pulse Rate During >21 to <=24 Months of Participant's Age | Pulse rate of participants in beats per minute was reported. | Any visit during participants' age above 21 Months and up to 24 Months | 
| Pulse Rate During >24 to <=30 Months of Participant's Age | Pulse rate of participants in beats per minute was reported. | Any visit during participants' age above 24 Months and up to 30 Months | 
| Temperature During 0 to Less Than or Equal to (<=) 2 Months of Participant's Age | Temperature of participants in degree Celsius was reported. | Any visit during participants' age from 0 to 2 Months | 
| Temperature at 8 Months of Participant's Age | Temperature of participants in degree Celsius was reported. | At 8 Months of participants' age | 
| Temperature at 15 Months of Participant's Age | Temperature of participants in degree Celsius was reported. | At 15 Months of participants' age | 
| Temperature During 0 to <=3 Months of Participant's Age | Temperature of participants in degree Celsius was reported. | Any visit during participants' age from 0 to 3 Months | 
| Temperature During >3 to <=6 Months of Participant's Age | Temperature of participants in degree Celsius was reported. | Any visit during participants' age above 3 Months and up to 6 Months | 
| Temperature During >6 to <=9 Months of Participant's Age | Temperature of participants in degree Celsius was reported. | Any visit during participants' age above 6 Months and up to 9 Months | 
| Temperature During >15 to <=18 Months of Participant's Age | Temperature of participants in degree Celsius was reported. | Any visit during participants' age above 15 Months and up to 18 Months | 
| Temperature During >21 to <=24 Months of Participant's Age | Temperature of participants in degree Celsius was reported. | Any visit during participants' age above 21 Months and up to 24 Months | 
| Temperature During >24 to <=30 Months of Participant's Age | Temperature of participants in degree Celsius was reported. | Any visit during participants' age above 24 Months and up to 30 Months | 
| Respiratory Rate During 0 to Less Than or Equal to (<=) 2 Months of Participant's Age | Respiratory rate of participants in breaths per minute was reported. | Any visit during participants' age from 0 to 2 Months | 
| Respiratory Rate at 8 Months of Participant's Age | Respiratory rate of participants in breaths per minute was reported. | At 8 Months of participants' age | 
| Respiratory Rate at 15 Months of Participant's Age | Respiratory rate of participants in breaths per minute was reported. | At 15 Months participants' age | 
| Respiratory Rate During 0 to <=3 Months of Participant's Age | Respiratory rate of participants in breaths per minute was reported. | Any visit during participants' age from 0 to 3 Months | 
| Respiratory Rate During >3 to <=6 Months of Participant's Age | Respiratory rate of participants in breaths per minute was reported. | Any visit during participants' age above 3 Months and up to 6 Months | 
| Respiratory Rate During >6 to <=9 Months of Participant's Age | Respiratory rate of participants in breaths per minute was reported. | Any visit during participants' age above 6 Months and up to 9 Months | 
| Respiratory Rate During >15 to <=18 Months of Participant's Age | Respiratory rate of participants in breaths per minute was reported. | Any visit during participants' age above 15 Months and up to 18 Months | 
| Respiratory Rate During >21 to <=24 Months of Participant's Age | Respiratory rate of participants in breaths per minute was reported. | Any visit during participants' age above 21 Months and up to 24 Months | 
| Respiratory Rate During >24 to <=30 Months of Participant's Age | Respiratory rate of participants in breaths per minute was reported. | Any visit during participants' age above 24 Months and up to 30 Months | 
| Number of Participants With Abnormal Neurological Examination Findings During 0 to Less Than or Equal to (<=) 2 Months of Participant's Age | Neurologic examination evaluated all cranial nerves except I (smell), IX (taste) and XI (shoulder shrug). Motor examination included evaluation of muscle tone, bulk and movement. Sensory examination included test of temperature and superficial pain (homologous dermatomes using cold tuning fork, neurological examination pin) and deep pain by pressure on achilles tendon. Reflex evaluation included biceps, brachioradialis, patellar, and achilles tendons. Evaluation for persistence of developmental reflexes including Moro reflex, palmar and planter grasp, and tonic neck response was evaluated. Autonomic nervous system evaluation included examination of pupillary reaction, heart rate changes in response to activity, and inquiring about abnormal sweating. Abnormality was determined by the assessor. | Any visit during participants' age from 0 to 2 Months | 
| Number of Participants With Abnormal Neurological Examination Findings at 8 Months of Participant's Age | Neurologic examination evaluated all cranial nerves except I (smell), IX (taste) and XI (shoulder shrug). Motor examination included evaluation of muscle tone, bulk and movement. Sensory examination included test of temperature and superficial pain (homologous dermatomes using cold tuning fork, neurological examination pin) and deep pain by pressure on achilles tendon. Reflex evaluation included biceps, brachioradialis, patellar, and achilles tendons. Evaluation for persistence of developmental reflexes including Moro reflex, palmar and planter grasp, and tonic neck response was evaluated. Autonomic nervous system evaluation included examination of pupillary reaction, heart rate changes in response to activity, and inquiring about abnormal sweating. Abnormality was determined by the assessor. | At 8 Months of participants' age | 
| Number of Participants With Abnormal Neurological Examination Findings at 15 Months of Participant's Age | Neurologic examination evaluated all cranial nerves except I (smell), IX (taste) and XI (shoulder shrug). Motor examination included evaluation of muscle tone, bulk and movement. Sensory examination included test of temperature and superficial pain (homologous dermatomes using cold tuning fork, neurological examination pin) and deep pain by pressure on achilles tendon. Reflex evaluation included biceps, brachioradialis, patellar, and achilles tendons. Evaluation for persistence of developmental reflexes including Moro reflex, palmar and planter grasp, and tonic neck response was evaluated. Autonomic nervous system evaluation included examination of pupillary reaction, heart rate changes in response to activity, and inquiring about abnormal sweating. Abnormality was determined by the assessor. | At 15 Months of participants' age | 
| Number of Participants With Abnormal Neurological Examination Findings at Follow-up Visit 1 (Month 20 of Participant's Age) | Neurologic examination evaluated all cranial nerves except I (smell), IX (taste) and XI (shoulder shrug). Motor examination included evaluation of muscle tone, bulk and movement. Sensory examination included test of temperature and superficial pain (homologous dermatomes using cold tuning fork, neurological examination pin) and deep pain by pressure on achilles tendon. Reflex evaluation included biceps, brachioradialis, patellar, and achilles tendons. Evaluation for persistence of developmental reflexes including Moro reflex, palmar and planter grasp, and tonic neck response was evaluated. Autonomic nervous system evaluation included examination of pupillary reaction, heart rate changes in response to activity, and inquiring about abnormal sweating. Abnormality was determined by the assessor. | Follow-up Visit 1 (At the age of Month 20) | 
| Number of Participants With Abnormal Neurological Examination Findings at Follow-up Visit 2 (Month 26 of Participant's Age) | Neurologic examination evaluated all cranial nerves except I (smell), IX (taste) and XI (shoulder shrug). Motor examination included evaluation of muscle tone, bulk and movement. Sensory examination included test of temperature and superficial pain (homologous dermatomes using cold tuning fork, neurological examination pin) and deep pain by pressure on achilles tendon. Reflex evaluation included biceps, brachioradialis, patellar, and achilles tendons. Evaluation for persistence of developmental reflexes including Moro reflex, palmar and planter grasp, and tonic neck response was evaluated. Autonomic nervous system evaluation included examination of pupillary reaction, heart rate changes in response to activity, and inquiring about abnormal sweating. Abnormality was determined by the assessor. | Follow-up Visit 2 (At the age of 26 Months) | 
| Bayley Infant Neurodevelopmental Screener (BINS) Total Score at Month 8 of Participant's Age | BINS: a validated instrument designed specifically for a high-risk infant population. It consisted of 11-13 items for different age levels (11 items for participants aged from 3-4 months, 11-15 months, 16-20 months; 13 items for participants aged from 5-6 months, 7-10 months, 21-24 months) to assess cognitive, social, language, gross, and fine motor skills. Each item was scored on a range 0 = non-optimal performance to 1 = optimal performance; BINS total score was sum of scores of each item and it ranged for 11 items from 0 (non-optimal performance) to 11 (optimum performance) and for 13 items from 0 (non-optimal performance) to 13 (optimum performance), higher score indicated better performance. | At 8 Months of participants' age | 
| Bayley Infant Neurodevelopmental Screener (BINS) Total Score at Month 15 of Participant's Age | BINS: a validated instrument designed specifically for a high-risk infant population. It consisted of 11-13 items for different age levels (11 items for participants aged from 3-4 months, 11-15 months, 16-20 months; 13 items for participants aged from 5-6 months, 7-10 months, 21-24 months) to assess cognitive, social, language, gross, and fine motor skills. Each item was scored on a range 0 = non-optimal performance to 1 = optimal performance; BINS total score was sum of scores of each item and it ranged for 11 items from 0 (non-optimal performance) to 11 (optimum performance) and for 13 items from 0 (non-optimal performance) to 13 (optimum performance), higher score indicated better performance. | At 15 Months of participants' age | 
| Bayley Infant Neurodevelopmental Screener (BINS) Total Score at Follow-up Visit 1 (Month 20 of Participant's Age) | BINS: a validated instrument designed specifically for a high-risk infant population. It consisted of 11-13 items for different age levels (11 items for participants aged from 3-4 months, 11-15 months, 16-20 months; 13 items for participants aged from 5-6 months, 7-10 months, 21-24 months) to assess cognitive, social, language, gross, and fine motor skills. Each item was scored on a range 0 = non-optimal performance to 1 = optimal performance; BINS total score was sum of scores of each item and it ranged for 11 items from 0 (non-optimal performance) to 11 (optimum performance) and for 13 items from 0 (non-optimal performance) to 13 (optimum performance), higher score indicated better performance. | Follow-up Visit 1 (At the age of Month 20) | 
| Bayley Infant Neurodevelopmental Screener (BINS) Total Score at Follow-up Visit 2 (Month 26 of Participant's Age) | BINS: a validated instrument designed specifically for a high-risk infant population. It consisted of 11-13 items for different age levels (11 items for participants aged from 3-4 months, 11-15 months, 16-20 months; 13 items for participants aged from 5-6 months, 7-10 months, 21-24 months) to assess cognitive, social, language, gross, and fine motor skills. Each item was scored on a range 0 = non-optimal performance to 1 = optimal performance; BINS total score was sum of scores of each item and it ranged for 11 items from 0 (non-optimal performance) to 11 (optimum performance) and for 13 items from 0 (non-optimal performance) to 13 (optimum performance), higher score indicated better performance. Data collected at age of 26 months used 24 months' age items. | Follow-up Visit 2 (At the age of Month 26) | 
| Bzoch-League Receptive Expressive Emergent Language Test 3rd Edition (REEL-3) Language Ability Score at Month 8 of Participant's Age | REEL-3, was designed to identify infants and toddlers who had language impairments or who had other disabilities that affect language development. Caregiver answered interview questionnaire by pediatrician, pediatric neurologist or clinical psychologist for receptive language and expressive language subtests. Each of these 2 sub tests had 66 questions with answer of 'yes = 1' or 'no = 0'. Sum of receptive and expressive language subtests answers was used to calculate REEL-3 language ability total score, with following ranges: <70 (very poor), 70-79 (poor), 80-89 (below average), 90-110 (average), 111-120 (above average), 121-130 (superior), and >130 (very superior). Higher scores indicated better language ability. | At 8 Months of participants' age | 
| Bzoch-League Receptive Expressive Emergent Language Test 3rd Edition (REEL-3) Language Ability Score at Month 15 of Participant's Age | REEL-3, was designed to identify infants and toddlers who had language impairments or who had other disabilities that affect language development. Caregiver answered interview questionnaire by pediatrician, pediatric neurologist or clinical psychologist for receptive language and expressive language subtests. Each of these 2 sub tests had 66 questions with answer of 'yes = 1' or 'no = 0'. Sum of receptive and expressive language subtests answers was used to calculate REEL-3 language ability total score, with following ranges: <70 (very poor), 70-79 (poor), 80-89 (below average), 90-110 (average), 111-120 (above average), 121-130 (superior), and >130 (very superior). Higher scores indicated better language ability. | At 15 Months of participants' age | 
| Bzoch-League Receptive Expressive Emergent Language Test 3rd Edition (REEL-3) Language Ability Score at Follow-up Visit 1 (Month 20 of Participant's Age) | REEL-3, was designed to identify infants and toddlers who had language impairments or who had other disabilities that affect language development. Caregiver answered interview questionnaire by pediatrician, pediatric neurologist or clinical psychologist for receptive language and expressive language subtests. Each of these 2 sub tests had 66 questions with answer of 'yes = 1' or 'no = 0'. Sum of receptive and expressive language subtests answers was used to calculate REEL-3 language ability total score, with following ranges: <70 (very poor), 70-79 (poor), 80-89 (below average), 90-110 (average), 111-120 (above average), 121-130 (superior), and >130 (very superior). Higher scores indicated better language ability. | Follow-up Visit 1 (At the age of Month 20) | 
| Bzoch-League Receptive Expressive Emergent Language Test 3rd Edition (REEL-3) Language Ability Score at Follow-up Visit 2 (Month 26 of Participant's Age) | REEL-3, was designed to identify infants and toddlers who had language impairments or who had other disabilities that affect language development. Caregiver answered interview questionnaire by pediatrician, pediatric neurologist or clinical psychologist for receptive language and expressive language subtests. Each of these 2 sub tests had 66 questions with answer of 'yes = 1' or 'no = 0'. Sum of receptive and expressive language subtests answers was used to calculate REEL-3 language ability total score, with following ranges: <70 (very poor), 70-79 (poor), 80-89 (below average), 90-110 (average), 111-120 (above average), 121-130 (superior), and >130 (very superior). Higher scores indicated better language ability. | Follow-up Visit 2 (At the age of Month 26) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Exposure in utero in tanezumab program