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An Open-label Extension Study To Evaluate Safety Of PF-06252616 In Boys With Duchenne Muscular Dystrophy

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ClinicalTrials.gov Identifier: NCT02907619
Recruitment Status : Terminated (Termination Date: 30Aug2018; Reason for termination: Lack of Efficacy)
First Posted : September 20, 2016
Results First Posted : November 25, 2019
Last Update Posted : November 25, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This study is an open-label extension to protocol B5161002 and will provide an assessment of the long term safety, efficacy, pharmacodynamics and pharmacokinetics of intravenous dosing of PF 06252616 in boys with Duchenne muscular dystrophy. Approximately 105 eligible subjects will be assigned to receive a monthly individualized maximum tolerated dose based on their tolerability profile/data from B5161002. This study will not contain a placebo comparator. Subjects will undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI), functional capacity evaluations (4 stair climb, range of motion, strength testing, Northstar Ambulatory Assessment, upper limb functional testing, six minute walk test and pulmonary function tests) and pharmacokinetic testing.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Biological: PF-06252616 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG TERM SAFETY OF PF-06252616 IN BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
Actual Study Start Date : October 13, 2016
Actual Primary Completion Date : November 22, 2018
Actual Study Completion Date : November 22, 2018


Arm Intervention/treatment
Experimental: PF-06252616
Either 5mg/kg, 20mg/kg or 40mg/kg will be assigned to a subject based on their maximum tolerated dose from B5161002
Biological: PF-06252616
Either 5mg/kg, 20mg/kg or 40mg/kg will be assigned to a subject based on their maximum tolerated dose from B5161002




Primary Outcome Measures :
  1. Number of Participants With Dose Reduced or Temporary Discontinuation Due to AEs [ Time Frame: 2 Years ]
    An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. Treatment-related AEs were determined by the investigator. The number of participants with dose reduced or temporary discontinuation due to both all-causality and treatment-related AEs are presented below.

  2. Number of Participants With Severe Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 2 Years ]
    An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator. The number of participants with severe all-causality and treatment-related TEAEs are presented below.

  3. Number of Participants Who Discontinued From the Study Due to TEAEs [ Time Frame: 2 Years ]
    An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. The number of participants who discontinued from the study due to both all-causality and treatment-related TEAEs are presented below.

  4. Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology [ Time Frame: 2 Years ]

    Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils and absolute monocytes.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

    (ULN=Upper Limit of Normal; LLN=Lower Limit of Normal).


  5. Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Coagulation [ Time Frame: 2 Years ]

    Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT).

    (ULN=Upper Limit of Normal). Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.


  6. Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function [ Time Frame: 2 Years ]

    Liver function evaluation included: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

    (LLN=Lower Limit of Normal; ULN=Upper Limit of Normal).


  7. Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Renal Function [ Time Frame: 2 Years ]

    Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (ULN=Upper Limit of Normal).


  8. Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes [ Time Frame: 2 Years ]

    Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate and bicarbonate.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

    (LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).


  9. Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones [ Time Frame: 2 Years ]

    Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

    (LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).


  10. Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry [ Time Frame: 2 Years ]

    Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, amylase, iron binding capacity, unsaturated iron binding capacity, transferrin saturation, iron and ferritin. Number of participants with iron abnormalities was reported in different age groups.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

    (LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).


  11. Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis [ Time Frame: 2 Years ]

    Urinalysis Microscopy included: urine red blood cell (RBC), urine white blood cell (WBC), urine uric acid crystals, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam.

    Urinalysis Dipstick included: urine pH, urine glucose, urine ketones, urine protein, urine blood/hemoglobin, urine nitrite, urine leukocyte esterase.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.


  12. Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Fecal Blood [ Time Frame: 2 Years ]

    Number of participants with blood detected in fecal samples is presented. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

    (ULN=Upper Limit of Normal).


  13. Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 37, 49, 61, 73 and 85. ]

    Participants were asked to fast for at least 8 hours prior to collection of blood to evaluate serum iron, serum ferritin and % transferrin saturation. The unit of iron was mcg/dL; the unit of ferritin was ng/mL; the unit of %transferrin saturation was %.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  14. Number of Participants With Significant Results of Physical Examinations Including Nose and Throat Mucosal Examinations [ Time Frame: 2 Years ]
    Physical examinations were conducted by a physician, trained physician's assistant, or nurse practitioner as acceptable according to local regulation. A targeted nose and throat mucosal exam was performed to monitor for any signs of mucosal telangiectasias. The clinically significant physical examination results were determined by the investigator.

  15. Summary of Pubertal Development by Tanner Stage [ Time Frame: Screening, Baseline, Week 49. ]

    Tanner staging was performed before the first dose of this study to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition.

    Participant's Week 97 visit within study B5161002 (parent study) was collected as screening data.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  16. Summary of Testicular Volume [ Time Frame: Screening, Baseline, Week 49. ]

    Testicular volume was used to monitor pubertal development. Participant's Week 97 visit within Study B5161002 (parent study) was collected as screening data in current study.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  17. Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline [ Time Frame: 2 Years ]

    The number of participants pre-dose supine blood pressure and pulse rate meeting categorical summarization criteria are recorded in this table.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

    (DBP=diastolic blood pressure, SBP=systolic blood pressure; The unit for blood pressure is: mmHg, the unit for pulse rate is: beats per minute [BPM])


  18. Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - Overall Baseline [ Time Frame: 2 Years ]

    The number of participants with data of pre-dose supine blood pressure meeting categorical summarization were recorded in this table.

    Overall Baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002.

    (DBP=diastolic blood pressure, SBP=systolic blood pressure; The unit for blood pressure is: mmHg).


  19. Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline [ Time Frame: 2 Years ]

    QTcF=QT/(60/Hour)**(1/3). Means of replicates were used in the calculations. QT=time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTcF=corrected QT (Fridericia correction). All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position.

    Baseline was defined as the average of the last triplicate pre-dose measurements prior to Day 1 in B5161004.


  20. Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - Overall Baseline [ Time Frame: 2 Years ]

    QT=time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTcF=corrected QT (Fridericia correction). All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position.

    Overall baseline was defined as the average of the last triplicate pre-dose measurements prior to the first day of dosing in study B5161002.


  21. Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria [ Time Frame: Screening and Week 49. ]

    Liver Magnetic Resonance Imaging (MRIs) were sent to an independent central radiology imaging facility for calculation of the average R2* value which was used to monitor for iron accumulation in the liver. Mean R2* values had been used in the calculations.

    Normal: R2* <= 75 Hz at 1.5 T or <=139 Hz at 3.0 T; Above Normal: R2* > 75 Hz and <= 190 Hz at 1.5 T or R2* > 139 Hz and <= 369 Hz at 3.0 T Mild overload: R2* > 190 Hz at 1.5 T or R2* > 369 Hz at 3.0 T Data from participant's Week 93 visit in Study B5161002 (parent study) were used for screening in the current study.


  22. Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - B5161004 Baseline [ Time Frame: Baseline and Week 49. ]
    The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from cardiac MRIs. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

  23. Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - Overall Baseline [ Time Frame: Baseline, Weeks 49, 97, 146. ]

    The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from cardiac MRIs.

    Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.


  24. Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - B5161004 Baseline [ Time Frame: Baseline, Week 49. ]

    The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from echocardiograms.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  25. Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - Overall Baseline [ Time Frame: Baseline, Weeks 49, 97, 146. ]

    The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from echocardiograms.

    Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.


  26. Bone Age to Chronological Age Ratio [ Time Frame: Baseline and Week 49. ]

    Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date - date of birth + 1)/365.25.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  27. Whole Body and Spine DXA: Bone Mineral Density Z-Score, Height Adjusted Over Time [ Time Frame: Screening (Week 97 visit within parent study B5161002) and Week 49 ]

    Bone mineral density (BMD) was monitored by dual energy x-ray absorptiometry (DXA). DXA scans were obtained to evaluate bone mineral density of the spine and whole body without head.

    The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was "below the expected range for age". If the Z-score was above -2 standard deviations, the result was "within the expected range for age".


  28. Number of Participants With Suicidal Ideation or Suicidal Behavior [ Time Frame: 2 Years ]
    The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. C-SSRS was conducted with the participant's caregiver/legal guardian on the participant's behalf throughout the study, rather than administering this evaluation directly with the study participants. If at any visit the participant endorsed a 4 or 5 on the C-SSRS ideation section or reported any suicidality behavior, then an evaluation of suicide risk (risk assessment) had to be completed and the participant must have been discontinued. The significant result of C-SSRS was determined by the investigator.


Secondary Outcome Measures :
  1. Change From Baseline on the 4 Stair Climb (4SC) - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49, 73. ]

    The 4SC quantified the time required for a participant to ascend 4 standard steps. The functional assessment of 4SC was conducted by a physiotherapist (or exercise physiologist). In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessments were completed at approximately the same time of day.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  2. Change From Baseline on the 4SC - Overall Baseline [ Time Frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170. ]

    The 4SC quantified the time required for a participant to ascend 4 standard steps. The functional assessment of 4SC was conducted by a physiotherapist (or exercise physiologist). In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessments were completed at approximately the same time of day.

    This is the overall change from baseline which included the change since enrolling in the parent study B5161002.

    Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.


  3. Change From Baseline on the Forced Vital Capacity (FVC) - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49 and 73. ]

    FVC was measured using the FVC maneuver by spirometry to evaluate respiratory muscle function. The best (largest) FVC measurement from a set of 3 was captured on the database.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  4. Change From Baseline on the FVC - Overall Baseline [ Time Frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170. ]

    Forced vital capacity (FVC) was measured using the FVC maneuver by spirometry to evaluate respiratory muscle function. The best (largest) FVC measurement from a set of 3 was captured on the database. This is the overall change from baseline which included the change since enrolling in the parent study B5161002.

    Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.


  5. Change From Baseline on the Northstar Ambulatory Assessment (NSAA) Score - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49, 73. ]

    The NSAA was a 17-item test that measured gross motor function. Each individual item was evaluated with either 0-unable to perform independently, 1-able to perform with assistance, 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function).

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  6. Change From Baseline on the NSAA Score - Overall Baseline [ Time Frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170. ]

    The NSAA was a 17-item test that measured gross motor function. Each individual item was evaluated with either 0-unable to perform independently, 1-able to perform with assistance, 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). This is the overall change from baseline which included the change since enrolling in the parent study B5161002.

    Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.


  7. Change From Baseline on the NSAA - Time to Stand From Supine - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49, 73. ]

    Rise from supine was a timed functional test within NSAA. This test of time-to-stand from supine was analyzed separately for summary tabulation along with the total NSAA score.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  8. Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline [ Time Frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170. ]

    Rise from supine was a timed functional test within NSAA. This test of time-to-stand from supine was analyzed separately for summary tabulation along with the total NSAA score. This is the overall change from baseline which included the change since enrolling in the parent study B5161002.

    Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.


  9. Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49, 73. ]

    A time to event analysis was performed for loss of ambulation. Loss of ambulation was defined as the inability to walk unassisted and without braces for at least 10 m, as assessed and reported by the investigator at each study visit, and confirmed by the inability to walk/run 10 m (as 1 component of the NSAA) evaluated at the next visit at which timed function tests were performed.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  10. Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline [ Time Frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170. ]

    A time to event analysis was performed for loss of ambulation. Loss of ambulation was defined as the inability to walk unassisted and without braces for at least 10 m, as assessed and reported by the investigator at each study visit, and confirmed by the inability to walk/run 10 m (as 1 component of the NSAA) evaluated at the next visit at which timed function tests were performed. This is the overall change from baseline which included the change since enrolling in the parent study B5161002.

    Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.


  11. Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49 and 73. ]

    ROM of the ankle was evaluated by goniometry and any occurrences of ankle contractures were recorded. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of ankle ROM was completed at approximately the same time of day.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  12. Change From Baseline on the Ankle ROM - Overall Baseline [ Time Frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170. ]

    ROM of the ankle was evaluated by goniometry and any occurrences of ankle contractures were recorded. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of ankle ROM was completed at approximately the same time of day. This is the overall change from baseline which included the change since enrolling in the parent study B5161002.

    Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.


  13. Change From Baseline on the Performance of Upper Limb (PUL) Overall Score - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49 and 73. ]

    The PUL scale was used to assess motor performance of the upper limb for individuals with DMD. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into 3 levels; shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 to 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores; shoulder maximum 16, middle level maximum score 34 and distal level maximum score 24. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of PUL was completed at approximately the same time of day.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  14. Change From Baseline on the PUL Overall Score - Overall Baseline [ Time Frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170. ]

    The PUL scale was used to assess motor performance of the upper limb for individuals with DMD. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into 3 levels; shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 to 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores; shoulder maximum 16, middle level maximum score 34 and distal level maximum score 24.

    This is the overall change from baseline which included the change since enrolling in parent study B5161002. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.


  15. Change From Baseline on the Six Minute Walk Distance (6MWD) - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49 and 73. ]

    The 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of 6MWD was completed at approximately the same time of day.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  16. Change From Baseline on the 6MWD - Overall Baseline [ Time Frame: Baseline,Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170. ]

    The 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of 6MWD was completed at approximately the same time of day. This is the overall change from baseline which included the change since enrolling in the parent study B5161002.

    Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was start of the study treatment in parent study B5161002.


  17. Change From Baseline on the Forced Expiratory Volume in One Second (FEV1) - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49 and 73. ]

    The FEV1 was recorded as an absolute volume in litres and in terms of predicted values according to age, height, race and gender. The best single FEV1 measurement from a set of 3 was recorded in the database.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  18. Change From Baseline on the Peak Expiratory Flow Rate (PEFR)- B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49 and 73. ]

    PEFR was one of the Pulmonary Function Tests (PFTs). Three technically adequate peak expiratory flow rate (PEFR) maneuvers were performed and reported in Litres/Minute (L/min), and the highest single PEFR was reported in the database. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of PEFR was completed at approximately the same time of day.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  19. Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline [ Time Frame: Baseline, Weeks 13, 25, 49, 73. ]

    Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, elbow extension, hip abduction and shoulder abduction. 95% Confidence Interval was not calculated when less than or equal to 3 participants' data were available.

    Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.


  20. Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline [ Time Frame: Baseline,Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170. ]

    Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, elbow extension, hip abduction and shoulder abduction. 95% Confidence Interval was not calculated when less than or equal to 3 participants' data were available.

    Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was start of the study treatment in parent study B5161002.


  21. Serum PF-06252616 (Domagrozumab) Concentration Versus Time Summary [ Time Frame: Weeks 1, 25, 49 and 73 ]
  22. Number of Participants With Anti-drug Antibodies (ADA) Development [ Time Frame: Weeks 1, 25, 49, 73 and Early Termination ]
    The criterion for positive result of ADA samples was ADA titer >=1.88. The criterion for negative result of ADA samples was ADA titer <1.88.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects with Duchenne muscular dystrophy who enrolled and completed study B5161002.
  2. Signed and dated informed consent document (ICD) indicating that the subject's parent or legal guardian/caregiver has been informed of all pertinent aspects of the study.
  3. Subjects and their legal guardians/caregivers who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  4. Subject have;

    1. Adequate hepatic function on screening laboratory assessments
    2. GLDH less than 20 units/liter (2 x upper limit of normal [ULN])
    3. Iron content estimate on the liver MRI within the normal range.

Exclusion Criteria:

  1. Unwilling or unable (eg, metal implants) to undergo examination with closed MRI.
  2. All male subjects who are able to father children and are sexually active and at risk for impregnating a female partner, who are unwilling or unable to use a highly effective method of contraception. In addition, all sexually active male subjects who are unwilling or unable to prevent potential transfer of and exposure to drug through semen to their partners by using a condom consistently and correctly. .
  3. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are related to Pfizer employees directly involved in the conduct of the study.
  4. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.
  5. Participation in other studies involving investigational drug(s), with the exception of B5161002.
  6. History of allergic or anaphylactic reaction to a therapeutic or diagnostic protein or additives of this investigational product.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02907619


  Show 47 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] April 8, 2016
Statistical Analysis Plan  [PDF] June 18, 2019


Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02907619     History of Changes
Other Study ID Numbers: B5161004
2016-001615-21 ( EudraCT Number )
First Posted: September 20, 2016    Key Record Dates
Results First Posted: November 25, 2019
Last Update Posted: November 25, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Duchenne muscular dystrophy, myostatin, open-label
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked