Clinical trial NCT02326454: A Placebo Controlled Study of MR901 (Talaporfin Sodium Sodium + a Drug-activating Device) for the Relief of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia
Official title: A Phase 2 Randomised, Double-blind, Placebo Controlled, Study of MR901 in Patients With Moderate to Severe Lower Urinary Tract Symptoms (LUTS) Due to Benign Prostatic Hyperplasia (BPH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Benign Prostatic Hyperplasia
Lead sponsor: Light Sciences Oncology
Sponsor class: INDUSTRY
Collaborators: name: Mundipharma Research Limited
First posted: 2014-12-29
Enrollment: 225
Sex: MALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study investigates the safety and efficacy of a photosensitive drug (talaporfin sodium) activated by an intraurethrally placed drug-activating device. MR901 is a code used to identify the combination of talaporfin sodium and the drug-activating device. Two different light doses will be tested against placebo groups in this 4-arm study.

Detailed description: At least 192 patients with moderate-to-severe LUTS caused by BPH will be randomized in a 2:2:1:1 ratio to receive a single treatment of talaporfin sodium activated by light at one of two light doses or placebo (saline) with light at either dose. Follow-up is planned for 52 weeks from the day of treatment, with assessment at 12 weeks for change in International Prostate Symptom Score and continued follow-up during the remaining 40 weeks to assess duration of effect, need for any intervention, and longer-term safety.

Eligibility criteria: Inclusion criteria:

1. Males aged ≥40 years, weighing ≤200 Kg and able to provide written, informed consent.
2. Documented symptoms of BPH-LUTS for 6 months or more.
3. For patients regularly taking their prescribed BPH medication, dose should have been stable for at least 6 months for 5-alpha reductase inhibitors and 3 months for other BPH medications.
4. For patients who have withdrawn from regularly taking their prescribed BPH medication, there should have been a 6 month washout period for 5-alpha reductase inhibitors and 3 months for other BPH medications.
5. Have a total International Prostate Symptom Score (IPSS; Qs 1-7) of ≥ 15 at both V1 and V2 with a difference between those visits of ≤ 4 points.
6. Prostate volume of 30 - 80 mL (inclusive).
7. Maximum urinary flow rate (Qmax): 5 - 15 mL/sec (assessed on two voids each of ≥ 150mL).
8. Prostate-specific antigen (PSA) ≤10 ng/mL.
9. Post-void residual (PVR) volume ≤200 mL measured by a urinary catheter or bladder ultrasound according to local standard practice.
10. Prostatic urethral length (PUL) of between 30 - 55mm (inclusive) as measured by TRUS.
11. Willing and able to comply with photosensitivity precautions

Exclusion criteria

1. Any minimally invasive or surgical treatment within the last 12 months, and is not currently undergoing intraprostatic injections for BPH or any other prostatic condition. In any case, all enrolled subjects must have, at Baseline cystoscopy, an appearance/presentation of the prostate that is consistent with BPH and compatible with possible response to the study test treatment.
2. Subjects weighing \>200 Kg.
3. Subjects with a history or current evidence of any of the following:

   1. A bladder disease or condition co-exists, such as idiopathic over-active bladder (OAB) and is evaluated by the Investigator as the predominant etiology for the subject's voiding symptomatology. A score of 4 points or greater on the 3 item OAB Awareness Tool (OABV3) or a high rate of urinary frequency (\>13xday and/or 4x/night) would require investigator specific evaluation in ascribing these symptoms to a bladder condition as opposed to lower urinary tract obstruction. i) If the former is the assessment, then the subject requires exclusion from the study. ii) If the latter is the assessment, then the subject may be deemed eligible for inclusion.

      The subject eligibility explanation must be captured in the patient source documents.
   2. Active urinary tract infection i.e. must have a screening urinalysis without signs of infection or negative urine culture. Must not have had a previous symptomatic urinary tract infection within 4 weeks of the study.
   3. Urethral stricture or any other anatomical feature that would complicate catheterisation.
   4. Interstitial cystitis.
   5. Predominant prostate middle lobe, as determined by the Investigator.
   6. Prostate or bladder cancer or bladder carcinoma-in-situ - in particular, evidence from digital rectal exam (DRE) of prostate abnormalities suggestive of cancer in the last 12 months.
   7. Any other absolute indication for urosurgical intervention (such as acute or frequent retention, currently untreated bladder or urethral stones, urethral strictures/bladder neck contracture (BNC)).
   8. Damage to the bladder neck which could interfere with study procedures.
4. PSA level in excess of \>10 ng/ml. If the PSA measurement is 2.5-10 ng/ml and/or has shown a clinically significant concerning increase in the last 6 months, local standard of care must be pursued to ensure the possibility of prostate cancer has been followed up and ruled out prior to study entry.
5. Subjects who had had a prostate biopsy within 6 weeks prior to Screening.
6. Any neurological condition affecting the bladder or a history of a neurogenic or chronically decompensated bladder i.e. neurogenic bladder, Parkinson's disease, history of chronic prostatitis within the last 5 years.
7. Prior treatment for urinary incontinence.
8. Requirements for daily incontinence pads or devices.
9. Subjects in whom nocturia is due to etiologies other than their BPH-LUTS, such as neurogenic bladder, diabetic neuropathy, neurocongestive heart failure, hepatic failure, nephritic syndrome, sleep disorder.
10. Previous or concurrent clinically relevant cardiovascular or cerebrovascular disorder within 24 weeks prior to the study i.e. unstable angina pectoris, myocardial infarction, transient ischemic attack, or cerebrovascular accident (stroke) within the past 6 months, or peripheral arterial disease with intermittent claudication or Leriche's syndrome.
11. Presence of serious hepatic diseases, renal diseases, immunological diseases, or pulmonary diseases that are clinically relevant.
12. Unwilling to use contraception for 3 months following administration of study medication or with an interest in future fertility.
13. A prolonged QTcF interval at baseline and/or who are currently taking medication that prolongs QT interval ("prolonged QTcF interval" defined as \> 450 ms).
14. Known sensitivity to porphyrin-type drugs or known history of porphyria.
15. Any contraindications to use of the study treatment.
16. Active alcohol or drug abuse.
17. Subject has clinical laboratory test results outside the reference ranges of the testing laboratory that are deemed to be clinically significant. Subjects with isolated test results that are outside the specified ranges and that are assessed as clinically insignificant will be allowed at the discretion of the Investigator, after discussion with the Sponsor's Medical Monitor/Study Physician, if appropriate. If a subject has 1 isolated test result outside the specific range that is deemed potentially clinically significant, rescreening may be allowed at the discretion of the Investigator, after discussion with the Medical Monitor/Study Physician
18. Subjects with known disorders of coagulation, apart from those receiving anticoagulant / antithrombotic / antiplatelet therapy in whom the dose of such medication must have been stable for at least 1 month prior to randomisation. In those receiving Vitamin K antagonists (warfarin, acenocoumarol, phenindione, etc) the INR value at baseline should be \<3.0.
19. Inability or unwillingness to comply with the required photosensitivity precautions during the three weeks following study treatment.
20. Subjects taking medications with a recognised propensity for causing photosensitivity (such as amiodarone, tetracyclines, sulphonamides) that cannot be discontinued for the initial study period, namely from 14 days prior to administration of study medication until 28 days afterwards.
21. Subjects with medical or investigation results deemed unfit for study treatment, as determined by medical history, clinical laboratory tests, ECG results, and physical examination that, in the Investigator's opinion, preclude entry into the study.
22. Subjects who have received an investigational medicinal product within 30 days or 5 half-lives of the investigational product prior to study entry (defined as the start of the Screening Period).
23. Subjects who are incapable of giving informed consent or complying with the protocol.

Primary outcomes:
measure: International Prostate Symptoms Score (IPSS) Questionnaire
timeFrame: 12 weeks
Secondary outcomes:
measure: Modified International Prostate Symptoms Score (IPSS) Questionnaire
timeFrame: 1, 2 and 3 Weeks
measure: Patient Global Impression of Improvement (PGI-1)
timeFrame: 4, 12, 26 and 52 weeks
measure: Clinical Global Impression of Improvement (CGI-1)
timeFrame: 4, 12, 26 and 52 weeks
measure: Maximum Urinary Flow Rate (Qmax)
timeFrame: 1, 2, 3, 4, 12, 26 and 52 weeks
measure: Post-void residual volume (PVR volume)
timeFrame: 1, 2, 3, 4, 12, 26 and 52 weeks
measure: 3-Day Frequency/Volume Data
timeFrame: 1, 2, 3, 4, 12, 26 and 52 weeks
measure: Safety and tolerability assessed by the number of subjects with Adverse Events
timeFrame: 52 weeks
measure: Prostate-specific Antigen (PSA)
timeFrame: 1, 2, 3, 4, 12, 26 and 52 weeks
measure: Duration of effect/time to next treatment and treatment selected
timeFrame: 52 weeks
measure: International Index of Erectile Function-15 (IIEF-15)
timeFrame: 4, 12, 26 and 52 weeks
measure: Quality of Life evaluation - Bother Score
timeFrame: 1, 2, 3, 4, 12, 26 and 52 weeks
measure: Over-active Bladder-V3 (OAB-V3)
timeFrame: 1, 2, 3, 4, 12, 26 and 52 weeks
measure: International Prostate Symptoms Score (IPSS) Questionnaire
timeFrame: 4, 26 and 52 weeks
measure: IPSS Subscores.
timeFrame: 1, 2, 3, 4, 12, 26 and 52 weeks
measure: Prostate volume
timeFrame: Baseline and 12 weeks
measure: Quality of Life evaluation - BPH Impact Index (BPHII)
timeFrame: 4, 12, 26 and 52 weeks
Other outcomes:
Locations:
city: Anniston
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Anchorage
country: United States
state: Alaska
city: Laguna Hills
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Murrieta
country: United States
state: California
city: San Diego
country: United States
state: California
city: Tarzana
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Aventura
country: United States
state: Florida
city: Bradenton
country: United States
state: Florida
city: Coral Gables
country: United States
state: Florida
city: Pompano Beach
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Bloomington
country: United States
state: Indiana
city: Greenwood
country: United States
state: Indiana
city: New Orleans
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Greenbelt
country: United States
state: Maryland
city: Towson
country: United States
state: Maryland
city: Chestnut Hill
country: United States
state: Massachusetts
city: Las Vegas
country: United States
state: Nevada
city: Edison
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Garden City
country: United States
state: New York
city: New York
country: United States
state: New York
city: Newburgh
country: United States
state: New York
city: Poughkeepsie
country: United States
state: New York
city: Concord
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Middleburg Heights
country: United States
state: Ohio
city: Springfield
country: United States
state: Oregon
city: Bala-Cynwyd
country: United States
state: Pennsylvania
city: Bryn Mawr
country: United States
state: Pennsylvania
city: Myrtle Beach
country: United States
state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Mountlake Terrace
country: United States
state: Washington
Study officials:
affiliation: LSO
name: Lisa Koch-Hulle
References: