E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
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 evaluate the efficacy of TRM-201 (rofecoxib) 17.5 mg versus placebo in patients with hemophilic arthropathy as measured by patient assessment of hemophilic arthropathy average pain intensity. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of TRM-201 (rofecoxib) 17.5 mg versus placebo on physical function in patients with hemophilic arthropathy as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function-Short Form 10a. 2. To evaluate the efficacy of TRM-201 (rofecoxib) 17.5 mg versus placebo in patients with hemophilic arthropathy as measured by patient assessment of hemophilic arthropathy worst pain intensity. 3. To evaluate the efficacy of TRM-201 (rofecoxib) 17.5 mg versus placebo in patients with hemophilic arthropathy as measured by the Pain Interference Domain from the Brief Pain Inventory (BPI). 4. To evaluate the efficacy of TRM-201 (rofecoxib) 17.5 mg versus placebo in patients with hemophilic arthropathy as measured by patient assessment of average hemophilic arthropathy pain intensity in the selected most painful joint. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of hemophilia A or B • Either on a stable prophylaxis regimen for their bleeding disorder (factor, bypassing agent, or nonfactor product therapy) OR currently taking or agree to initiate a gastroprotective agent (esomeprazole) for the duration of the trial • Diagnosis of Hemophilic Arthopathy for at least 6 months prior to screening • Chronic symptomatic pain in one or more joint(s) on 20 of the 30 days prior to screening. • Able and willing to wash out of non-study analgesic medications/agents for at least 5 days prior to Randomization including: acetaminophen (paracetamol), NSAIDs, opioids, cannabinoids, topical analgesics, benzodiazepines, gabapentin/pregabalin-containing products and other antiepileptic drugs used for pain • Primary source of pain is due to Hemophilic Arthropathy
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E.4 | Principal exclusion criteria |
• Taking opioids for greater than 4 days per week prior to screening • Has a history of advanced renal disease or severe liver disease (within the last 6 months) • Receiving emicizumab while also receiving activated prothrombin complex concentrate (FEIBA) • Uncontrolled or poorly controlled hypertension • History of major cardiac or cerebrovascular disease • History of an upper GI perforation, obstruction, or major GI bleed or current evidence of GI bleeding • Has active hepatitis C or hepatitis B infection or uncontrolled HIV. Note: Patients who are HIV positive are allowed to participate if considered to be controlled. • Has a positive drug screen for all prohibited drugs of potential abuse at screening • Has had an intra-articular injection (within 3 months), initiated physical therapy (within 30 days) or has had orthopedic surgery (within 4 months) prior to screening
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from baseline in the patient assessment of the daily hemophilic arthropathy pain score (average pain over the past 24 hours on a 0- to 10-point numeric rating scale) at Week 12 (assessed daily). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. The change from baseline in the PROMIS Physical Function-Short Form 10a score at Week 12 (assessed once weekly). 2. The change from baseline in the patient assessment of the daily hemophilic arthropathy pain score (worst pain over the past 24 hours on a 0- to 10-point numeric rating scale) at Week 12 (assessed daily). 3. The change from baseline in the Pain Interference score from the BPI at Week 12 (assessed once weekly). 4. The change from baseline in the patient assessment of hemophilic arthropathy pain intensity in the selected most painful joint (average pain over the past 24 hours) at Week 12 (assessed once weekly). Note: The same joint is to be followed throughout Part I.
Other Secondary Endpoints 1. The change from baseline in the PROMIS Sleep Disturbance-Short Form 4a score at Week 12 (assessed at clinic visits). 2. The change from baseline in the PGI-S – Joint Symptoms (assessed at baseline and end of Part I). 3. The change from baseline in the EQ-5D-5L Health Status score at Week 12 (assessed at clinic visits). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | No |
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 |
Australia |
Brazil |
Canada |
Russian Federation |
Turkey |
Ukraine |
United States |
Italy |
Poland |
Spain |
United Kingdom |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |