Chronic Pancreatitis
Conditions
Brief summary
Tanezumab is effective in reducing the pain associated with chronic pancreatitis.
Detailed description
On 23 Dec 2010 the FDA imposed a clinical halt for anti-NGF compounds due to safety reasons, ie, a case of osteonecrosis which occurred in relation to an anti-NGF compound of another company. All indications with the exception of Cancer Pain are affected resulting in termination of all studies in respective indications. Recruitment of Study A4091044 was stopped effective 27 Dec 2010. Two patients recruited so far did not receive further doses and were followed up for safety until LSLV on 22 Mar 2011.
Interventions
BIOLOGICALTanezumab
single administration of tanezumab 20 mg sub-cutaneously
OTHERPlacebo
single administration of placebo to match tanezumab, sub-cutaneously
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Adult male or female * Written informed consent * Diagnosis of chronic pancreatitis based on imaging studies * Persistent abdominal pain due to chronic pancreatitis * Qualifying pain score during the pre-treatment period * Willing to comply with study visit schedule and study requirements including for women of child-bearing potential or male patients with female partners of child-bearing potential, the use of 2 forms of birth control
Exclusion criteria
* Pregnant women, lactating mothers, women suspected of being pregnant and women who wish to become pregnant during the course of the study * Chronic pancreatitis as a complication of pancreatic cancer or acute pancreatic duct obstruction * Pancreatic surgery, lithotripsy or endoscopist decompression within 3 months * History of alcoholism (within 1 year of screening) or concurrent alcohol abuse * History of cancer in the past years * Significant cardiac disease within 6 months * History, diagnosis or signs and symptoms of significant neurologic disease * Disqualifying laboratory values including Hepatitis B or C, HIV and drug test * Other medical condition that may interfere with study endpoints or safety of the patient as determined by the Investigator * Known history of rheumatoid arthritis * Avascular necrosis of the bone * History of trauma to a major joint Evidence of osteoarthritis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Chronic Pancreatitis Pain Intensity Score Over the Period From Week 1 to Week 8 | Baseline, Week 1 to 8 | Daily average chronic pancreatitis pain is assessed with an 11-point Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst possible pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average and Worst Chronic Pancreatitis Pain Intensity Score at Week 1, 2, 4, 6, 8, 12 and 16 | Baseline, Week 1, 2, 4, 6, 8, 12, 16 | Daily average chronic pancreatitis pain and worst chronic pancreatitis pain are assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). |
| Change From Baseline in Worst Chronic Pancreatitis Pain Intensity Score Over Week 1 to Week 8 Period | Baseline, Week 1 to 8 | Daily average worst chronic pancreatitis pain is assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). |
| Number of Participants With At Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average and Worst Chronic Pancreatitis Pain Intensity Score | Week 8 | Daily average chronic pancreatitis pain and worst chronic pancreatitis pain are assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). |
| Number of Participants With Cumulative Reduction From Baseline in Average and Chronic Pancreatitis Pain Intensity Score | Week 8 | Daily average chronic pancreatitis pain and worst chronic pancreatitis pain are assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). |
| Change From Baseline in Brief Pain Inventory - Short Form (BPI-sf) Average and Worst Pain Score at Week 8 and 16 | Baseline, Week 8, 16 | BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (question 5 consists of 7 items that assess level of interference of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item was answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure were scored by item, with lower scores indicated less pain or pain interference. |
| Change From Baseline in Brief Pain Inventory - Short Form (BPI-sf) Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and 16 | Baseline, Week 8, 16 | BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and question 5 consisted of 7 items that assess level of interference of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item was answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure was scored by item, with lower score indicated less pain or pain interference. The 7 items in question 5 were averaged to obtain pain interference index, range: 0 to 10; higher score=greater impairment. |
| Change From Baseline in Patient's Global Assessment (PGA) of Chronic Pancreatitis at Week 4, 8 and 16 | Baseline, Week 4, 8, 12 | Patient's Global Assessment of Chronic Pancreatitis is a global evaluation that utilizes a 5-point Likert scale with a score of 1 being the best (Very Good) and a score of 5 being the worst (Very Poor) for the following question: Considering all the ways your chronic pancreatitis affects you, how are you doing today?. |
| Number of Participants With Improvement of Greater Than or Equal to 2 Points From Baseline in Patient's Global Assessment (PGA) of Chronic Pancreatitis | Weeks 4, 8, 16 | Patient's Global Assessment of Chronic Pancreatitis is a global evaluation that utilizes a 5-point Likert scale with a score of 1 being the best (Very Good) and a score of 5 being the worst (Very Poor) for the following question: Considering all the ways your chronic pancreatitis affects you, how are you doing today?. |
| Number of Participants With Anti Drug Antibody | Baseline, Week 8, 16 | — |
| Neuropathy Impairment Score (NIS) | Baseline and Weeks 2, 4, 8, 16 | NIS: 74-item questionnaire assesses muscle weakness, reflexes and sensation; scored separately for left, right limbs (37 items for each side). Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS score range 0-244, higher score=greater impairment. |
| Number of Participants With Injection Site Reaction | Day 1 up to Week 16 | Assessment of the injection site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion). |
| Plasma Tanezumab Levels | Baseline (pre-dose), Week 2, 4, 8, 16 | — |
| Serum Nerve Growth Factor (NGF) Levels | Baseline (pre-dose), Week 8, 16 | — |
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 112 days after the dose of study medication (up to 113 days) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Baseline up to Week 16 | Laboratory analysis included blood chemistry, hematology, urinalysis, pregnancy test, glycosylated hemoglobin levels (HbA1c levels) test and blood alcohol test. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Baseline up to Week 16 | All standard intervals (PR, QRS, QT, QT interval corrected for heart rate using Fridericia's formula \[QTcF\], QT interval corrected for heart rate using Bazett's formula \[QTcB\], RR intervals and heart rate) were analyzed for ECG abnormalities. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Subcutaneous Doses | Day 1 | Number of participants who received the single dose of placebo are reported. |
Countries
United States
Participant flow
Pre-assignment details
Due to the United States Food and Drug Administration (FDA) clinical hold, the study was prematurely terminated and no participants were enrolled in planned reporting arm tanezumab 20 milligram (mg) treatment and hence tanezumab 20 mg could not be administrated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo A single dose of placebo matched to tanezumab 20 milligram (mg) injection subcutaneously on Day 1. | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Placebo |
|---|---|
| Age, Customized 18 to 44 years | 1 Participants |
| Age, Customized 45 to 64 years | 1 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Change From Baseline in Average Chronic Pancreatitis Pain Intensity Score Over the Period From Week 1 to Week 8
Daily average chronic pancreatitis pain is assessed with an 11-point Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: Baseline, Week 1 to 8
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Change From Baseline in Average and Worst Chronic Pancreatitis Pain Intensity Score at Week 1, 2, 4, 6, 8, 12 and 16
Daily average chronic pancreatitis pain and worst chronic pancreatitis pain are assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: Baseline, Week 1, 2, 4, 6, 8, 12, 16
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Change From Baseline in Brief Pain Inventory - Short Form (BPI-sf) Average and Worst Pain Score at Week 8 and 16
BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (question 5 consists of 7 items that assess level of interference of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item was answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure were scored by item, with lower scores indicated less pain or pain interference.
Time frame: Baseline, Week 8, 16
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Change From Baseline in Brief Pain Inventory - Short Form (BPI-sf) Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and 16
BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and question 5 consisted of 7 items that assess level of interference of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item was answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure was scored by item, with lower score indicated less pain or pain interference. The 7 items in question 5 were averaged to obtain pain interference index, range: 0 to 10; higher score=greater impairment.
Time frame: Baseline, Week 8, 16
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Change From Baseline in Patient's Global Assessment (PGA) of Chronic Pancreatitis at Week 4, 8 and 16
Patient's Global Assessment of Chronic Pancreatitis is a global evaluation that utilizes a 5-point Likert scale with a score of 1 being the best (Very Good) and a score of 5 being the worst (Very Poor) for the following question: Considering all the ways your chronic pancreatitis affects you, how are you doing today?.
Time frame: Baseline, Week 4, 8, 12
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Change From Baseline in Worst Chronic Pancreatitis Pain Intensity Score Over Week 1 to Week 8 Period
Daily average worst chronic pancreatitis pain is assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: Baseline, Week 1 to 8
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Neuropathy Impairment Score (NIS)
NIS: 74-item questionnaire assesses muscle weakness, reflexes and sensation; scored separately for left, right limbs (37 items for each side). Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS score range 0-244, higher score=greater impairment.
Time frame: Baseline and Weeks 2, 4, 8, 16
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Number of Participants With Anti Drug Antibody
Time frame: Baseline, Week 8, 16
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Number of Participants With At Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average and Worst Chronic Pancreatitis Pain Intensity Score
Daily average chronic pancreatitis pain and worst chronic pancreatitis pain are assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: Week 8
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
All standard intervals (PR, QRS, QT, QT interval corrected for heart rate using Fridericia's formula \[QTcF\], QT interval corrected for heart rate using Bazett's formula \[QTcB\], RR intervals and heart rate) were analyzed for ECG abnormalities.
Time frame: Baseline up to Week 16
Population: ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 Participants |
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities
Laboratory analysis included blood chemistry, hematology, urinalysis, pregnancy test, glycosylated hemoglobin levels (HbA1c levels) test and blood alcohol test.
Time frame: Baseline up to Week 16
Population: ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
Secondary
Number of Participants With Cumulative Reduction From Baseline in Average and Chronic Pancreatitis Pain Intensity Score
Daily average chronic pancreatitis pain and worst chronic pancreatitis pain are assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: Week 8
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Number of Participants With Improvement of Greater Than or Equal to 2 Points From Baseline in Patient's Global Assessment (PGA) of Chronic Pancreatitis
Patient's Global Assessment of Chronic Pancreatitis is a global evaluation that utilizes a 5-point Likert scale with a score of 1 being the best (Very Good) and a score of 5 being the worst (Very Poor) for the following question: Considering all the ways your chronic pancreatitis affects you, how are you doing today?.
Time frame: Weeks 4, 8, 16
Population: No efficacy analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Number of Participants With Injection Site Reaction
Assessment of the injection site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion).
Time frame: Day 1 up to Week 16
Population: Intent to treat (ITT) analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Injection Site Reaction | 1 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time frame: Baseline up to 112 days after the dose of study medication (up to 113 days)
Population: ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Secondary
Plasma Tanezumab Levels
Time frame: Baseline (pre-dose), Week 2, 4, 8, 16
Population: No pharmacokinetic analysis were performed as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Secondary
Serum Nerve Growth Factor (NGF) Levels
Time frame: Baseline (pre-dose), Week 8, 16
Population: No analysis was performed for this outcome measure as no tanezumab participant and only two placebo participants were randomized due to early study discontinuation of FDA clinical hold.
Other Pre-specified
Number of Participants With Subcutaneous Doses
Number of participants who received the single dose of placebo are reported.
Time frame: Day 1
Population: ITT analysis set included all randomized participants who received at least 1 dose of subcutaneous study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Subcutaneous Doses | 2 Participants |