E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Medical condition in which the bone marrow makes too many red blood cells. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036061 |
E.1.2 | Term | Polycythemia vera |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
Evaluate the efficacy of ISIS 702843 to reduce the frequency of phlebotomy throughout the last 20 weeks of the Treatment Period |
|
E.2.2 | Secondary objectives of the trial |
- Evaluate the efficacy of ISIS 702843 to decrease the frequency of phlebotomy by various thresholds throughout the last 20 weeks of the Treatment Period - Evaluate the efficacy of ISIS 702843 to improve the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score (TSS) at Week 37 Exploratory Objectives • Evaluate the efficacy of ISIS 702843 to control Hct without phlebotomy throughout the last 20 weeks of the Treatment Period • Evaluate the impact of ISIS 702843 on serum hepcidin • Evaluate the impact of ISIS 702843 on measures of iron deficiency • Evaluate the impact of ISIS 702843 on serum erythropoiesis biomarkers and hematological variables ...omissis.... Safety Objectives • Evaluate the safety and tolerability of multiple doses of ISIS 702843 in patients with PD-PV PK Objectives • Evaluate PK exposure over time and potential PK/PD correlation on relevant biomarkers and efficacy outcome measures
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Meet modified World Health Organization (WHO) 2016 diagnostic criteria for polycythemia vera (PV) at the time of clinical diagnosis 2. Participant must be phlebotomy dependent 3. The participant's cytoreductive therapy must either be discontinued at least 3 months prior to Screening, OR participant must be on a stable dose for at least 3 months prior to Screening
|
|
E.4 | Principal exclusion criteria |
1. Meets criteria for post-polycythemia vera myelofibrosis (PPV-MF) as defined by the International Working Group- Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 2. Moderate to severe splenic pain or spleen-related organ obstruction 3. Active or chronic bleeding within 1 month of Screening, significant concurrent/recent coagulopathy, history of immune thrombocytopenic purpura (ITP) 4. Known primary or secondary immunodeficiency 5. Active infection with human immunodeficiency virus (HIV), hepatitis C, or hepatitis B. 6. Active infection requiring systemic antiviral or antimicrobial therapy or active novel coronavirus disease (Covid-19) infection 7. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or non-metastatic prostate cancer that has been successfully treated 8. Surgery requiring general anesthesia within 1 month prior to Screening
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Reduction in the frequency of phlebotomy comparing Baseline with the last 20 weeks of the 37-week Treatment Period |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Proportion of patients achieving a reduction in the frequency of phlebotomy by ≥ 30%, ≥ 50%, ≥ 75% and ≥ 90% comparing Baseline with the last 20 weeks of the 37-week Treatment Period [ Time Frame: Week 17 to Week 37 ]
- Change in the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF-TSS) From Baseline to Week 37 [ Time Frame: Baseline up to Week 37 ] |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Week 17 to week 37 - From Baseline to week 37 |
|
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 | Yes |
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 | 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 | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
Canada |
United States |
Poland |
Hungary |
United Kingdom |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 27 |