| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic pain including the pain of interstitial cystitis/painful bladder syndrome. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10008927 |
| E.1.2 | Term | Chronic interstitial cystitis |
|
| 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 |
To characterize the dose response for tanezumab when administered by SC injection at an 8-weekly interval (2 injections) for moderate to severe chronic pain associated with (IC/PBS).
To evaluate the safety and tolerability of tanezumab in the treatment of moderate to severe chronic pain associated with IC/PBS. |
|
| E.2.2 | Secondary objectives of the trial |
| To explore the response of IC/PBS urinary endpoints (eg, micturition frequency etc) to tanezumab compared to placebo. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Screen Visit 1
1. Patients must consent in writing to participate in the study by signing and dating an Informed Consent Document indicating that they have been informed of all pertinent aspects of the study prior to completing any of the Screening procedures.
2. Has an appropriate score on the Painful Bladder/Interstitial Cystitis Symptom Score (PBIC-SS), as outlined in the scoring guidance.
3. Male and female outpatients aged ≥18 years.
4. Female patients must meet one of the following criteria:
a. Female patients of non-childbearing potential: post-menopausal, defined as women who are ≥45 years old with amenorrhea for 24 consecutive months (regardless of FSH levels); amenorrhea for at least 1 year AND have a serum Follicle-Stimulating Hormone (FSH) level greater than 30 IU/L at Screening; or surgically sterile, defined as having had a hysterectomy and/or bilateral oophorectomy;
b. Female patients of child-bearing potential: must not be pregnant or lactating, and use adequate contraception (2 forms of birth control, one of which must be a barrier method).
Women of childbearing potential must have a negative serum pregnancy test at Screening (within 30 days prior to Baseline) and a negative urine pregnancy test at Baseline prior to initial dosing.
Male patients must agree that they and their female spouses/partners will use adequate contraception (2 forms of birth control, one of which must be barrier method) or be of non-childbearing potential.
Females of child-bearing potential and males must be willing to use approved methods of contraception from commencement of Screening procedures until 16 weeks after the last dose of study medication.
In the event of indeterminate or anomalous results on pregnancy/FSH testing or issues surrounding contraceptive requirements, study management should be contacted and will make the final decision as to the adequacy/need for contraception.
5. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, the self-completion of study questionnaires, electronic diary (eDiary), and other trial procedures.
6. Evidence of cystoscopy within 2 years of Screening to confirm the absence of significant lower urinary tract pathology, and the presence or absence of cystoscopic features of IC/PBS (eg, glomerulations, Hunner’s lesion).
Note: Cystoscopy is mandated within 2 years of Screening. Patients who have not had cystoscopy within 2 years of Screening must undergo the procedure at Screening.
Visit 2, Randomization.
The following continuation criteria have to be met in order for patients to be randomized:
7. Completes at least 4 average pain scores within any of the 7 days prior to randomization, with a mean average pain intensity score of ≥4 (0-10 NRS); the mean average pain intensity score at Baseline is defined as the mean of all 24-hour average pain intensity scores recorded in the 7 days before Visit 2 (Randomization).
8. Mean micturition frequency ≥ 8 per 24 hours over any 3 consecutive days in the previous 7 days prior to Visit 2 (Randomization).
9. Women of childbearing potential must have a negative urine pregnancy test at Visit 2 (Randomization) prior to initial dosing. |
|
| E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the study:
1. Pregnant women, lactating mothers, women suspected of being pregnant, and women who wish to be pregnant during the course of the clinical study.
2. Patients with symptoms of IC/PBS for less than 6 months prior to Screening.
3. Patients with a post-void residual (PVR) volume >200 mL at Screening (Visit 1).
4. Patients with a mean voided volume <40 and >400 mL per micturition as measured over 1 day of the 7-day eDiary period completed prior to Visit 2 (Randomization).
5. Patients with a total daily volume voided of >3500 mL, as confirmed by the eDiary completed prior to Visit 2 (Randomization).
6. Patients with greater than 1+ hematuria on dipstick test at Screening, unless fully investigated prior to randomization to rule out significant urological disease.
• Patients who are menstruating may be re-screened once menstruation has ceased if they have been found to have hematuria on dipstick testing.
7. Patients with a microbiologically-proven urinary tract infection at Screening (Visit 1) or Randomization (Visit 2). Patients can be treated and re-screened.
8. Patients with the following medical history and comorbid conditions at Screening [see protocol for table].
9. Patients who have undergone the following procedures [see protocol for table].
10. Patients with any of the following conditions at Screening:
• Indwelling urinary catheters or who perform Intermittent Self Catheterization (ISC).
• Passive urinary incontinence (e.g. vesicovaginal fistula).
• Not capable of independent voiding.
11. Patients at Screening (Visit 1) who intend to start bladder training program, electrostimulation/neuromodulation therapy (eg, Transcutaneous Electrical Nerve Stimulation (TENS)), acupuncture, or physiotherapy regimen during the study.
• Patients who are on an established regimen for at least 3 months prior to Screening may remain on this as long as it remains unchanged for the duration of the study.
12. Taking other treatments for interstitial cystitis at Screening as listed below [see protocol for table].
Patients are prohibited from taking those medications until Week 24, or Early Termination.
Note: Patients may remain on ongoing oral medications as background therapy for the treatment of their interstitial cystitis symptoms, provided that they have been administered at a stable dose for at least 3 months prior to Screening and for the duration of the study.
13. Patients who have participated in a previous tanezumab clinical study.
14. History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG-fusion protein.
15. Previous exposure to exogenous NGF or to an anti NGF antibody.
16. History of intolerance or hypersensitivity to acetaminophen (paracetamol) or any of its excipients, or existence of a medical condition or concomitant medication for which the use of acetaminophen is contraindicated (refer to product labeling).
17. Patients with a relevant neurological disease at Screening with which their urinary symptoms may be associated (eg, multiple sclerosis, Parkinson’s disease, spinal cord injury, spinal cord lesion, familial neuropathy, spina bifida or diabetic cystopathy); history, diagnosis, or signs and symptoms of clinically significant neurological disease, including but not limited to:
• Alzheimer’s disease or other types of dementia.
• Clinically significant head trauma within the past year
• Peripheral neuropathy
• Epilepsy or seizure
• Myopathy
18. History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder, including but not limited to:
• Psychotic disorders
• Somatoform disorders
• Bipolar disorders
• Any other psychiatric illness that in the opinion of the Investigator would render a patient unsuitable to participate in the study.
19. Hospital admission for depression or suicide attempt within 5 years of Screening or active, severe major depression at Screening (determined from medical history; if needed, severity of depression may be assessed using the Patient Health Questionnaire [PHQ-9]). A score ≥15 on questions 1-9 of the PHQ-9 corresponds to severe major depression.
20. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3.0 times the upper limit of normal at Screening Visit 1 (each confirmed by a repeat test) or any other laboratory abnormality that in the opinion of the Investigator would contraindicate study participation.
21. Estimated Glomerular Filtration Rate (eGFR by Cockcroft-Gault formula) ≤30 mL/min estimated from serum creatinine, body weight, age and gender at Screening(Visit 1).
22. Patients with Type I or type II diabetes mellitus who have an HbA1c > 8.0% |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is change from Baseline in mean average daily pain over 7 days at Week 16 as measured by an 11-point Numeric Rating Scale (NRS). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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.8.3 |
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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 29 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
| The End of Trial is defined as the date the last patient completes the Week 24 or Early Termination visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 21 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 21 |
Print
