E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paroxysmal Nocturnal Hemoglobinuria (PNH) |
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E.1.1.1 | Medical condition in easily understood language |
Rare blood disorder that that causes red blood cells to break down earlier than they should |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055629 |
E.1.2 | Term | Paroxysmal nocturnal hemoglobinuria |
E.1.2 | System Organ Class | 100000004857 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and efficacy of long-term therapy with ACH-0144471 in patients with PNH |
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E.2.2 | Secondary objectives of the trial |
To evaluate health-related quality of life measures in patients with PNH based on patient-reported outcome instruments and its evolution over the course of long-term therapy with ACH-0144471 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must have completed treatment in study ACH471-100 and must have demonstrated a clinical benefit from ACH-0144471, in the opinion of the PI, with no significant safety or tolerability concerns.
2. Female participants of childbearing potential must agree to use an acceptable method of contraception (as defined in Section 5.5.4) from the date of signing the informed consent to the first day of dosing (Day 1), and must agree to use a highly effective method of contraception (as defined in Section 5.5.4) from the first day of dosing to 30 days after their last dose of study drug. Female participants of childbearing potential must also have a negative serum pregnancy test during Screening and negative urine pregnancy test on Day 1.
Female participants of non-childbearing potential need not employ a method of contraception.
3. Non-sterile male participants must agree to use a highly effective method of contraception (as defined in Section 5.5.4) with their partner(s) of childbearing potential from the first day of dosing to 90 days after their last dose of study drug.
Males who are surgically sterile need not employ additional contraception.
Males must agree not to donate sperm while enrolled in this study and for 90 days after their last dose of study drug.
4. Must agree to provide written informed consent.
5. Must be willing, at all times, to have transportation and telephone access, and to be within one hour of an emergency medical center |
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E.4 | Principal exclusion criteria |
1. Have developed any clinically relevant co-morbidities while participating in ACH471-100 that would make the patient inappropriate for continuation of treatment with ACH-0144471, in the opinion of the investigator.
2. Have developed a clinically significant laboratory abnormality while participating in ACH471-100 that, in the opinion of the investigator, would make the patient inappropriate for the study or put the patient at undue risk.
3. Females who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration or patients with a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy will be evaluated by measuring LDH levels, Hgb levels, and reticulocyte counts at various time points during the study. The number and frequency of red blood cell transfusions will also be examined. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
continuously every 4 weeks, after 6 months every 8 weeks |
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E.5.2 | Secondary end point(s) |
To evaluate health-related quality of life measures in patients with PNH based on patient-reported outcome instruments and its evolution over the course of long-term therapy with ACH-0144471 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
QOL's assessed at approx. 3 months, 5 months then every 6 months. |
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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 | 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 | 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) | 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 | No |
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 | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 |
Italy |
Korea, Republic of |
New Zealand |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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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LVLS Patients may remain in the study until ACH-0144471 is commercially available in their country or the development of ACH-0144471 as a potential therapy for PNH is terminated, or until the therapy is no longer tolerated or effective or the Sponsor terminates the study at any time for any reason at the sole discretion of the sponsor.
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |