E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ebola Virus Disease |
Enfermedad por el virus del Ébola |
|
E.1.1.1 | Medical condition in easily understood language |
Ebola Virus Disease |
Enfermedad por el virus del Ébola |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014071 |
E.1.2 | Term | Ebola disease |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 safety and tolerability of CMX001 when administered for the treatment of EVD |
|
E.2.2 | Secondary objectives of the trial |
? To assess the effect of CMX001 treatment on survival in subjects with EVD through 28 days post-initiation of CMX001 therapy
? To describe the effect of CMX001 treatment on clinical outcomes (clinical progression defined as worsening of existing signs and symptoms; clinical improvement defined as improvement of clinical signs and symptoms; clinical resolution defined as resolution of clinical signs and symptoms) in patients treated for EVD
? To describe the virologic response (blood and stool EBOV viral load as measured by polymerase chain reaction [PCR] assay) to CMX001 treatment in subjects with EVD
? To evaluate the association between the virologic response and subject survival
? To characterize the emergence of viral resistance in CMX001-treated subjects with EVD
? To describe the plasma concentrations of BCV and CDV in CMX001-treated subjects |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, aged 2 months and older.
2. Have at least one positive EBOV PCR test (any body fluid) from the local virology laboratory.
3. Able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant GI events/medical history). [Note: With the prior approval of the Chimerix medical monitor (or designee), subjects who can be dosed using liquid suspension formulation or dispersed tablet through a gastrostomy tube or other feeding tube that allows study drug to be delivered directly into the subject?s stomach or intestine may be enrolled in the study. Intrajejunal delivery of CMX001 is not advised as no PK or tolerability data are available for this route of administration.]
4. If a male of reproductive potential, willing to use an acceptable contraceptive method(s) during sexual intercourse with a female partner of reproductive potential throughout the duration of his participation in the study and for at least 6 months after the last CMX001 dose administration.
5. If a female of reproductive potential, i.e., not premenarche, postmenopausal, surgically sterile, or documented ovarian failure, willing to use two acceptable contraceptive methods, one of which must be a barrier method, during sexual intercourse with a non-sterile male partner, throughout the duration of her participation in the study and for at least 6 months after the last CMX001 dose administration. [Note: For assessing inclusion criterion 4 or 5, a promise to abstain from sexual intercourse is not an acceptable method of preventing pregnancy for the purposes of this study. However, subjects who are currently sexually abstinent and who indicate a willingness to use an acceptable contraceptive method(s), as described above, should they begin or resume sexual activity may be enrolled into the study.]
6. Willing and able to understand and provide written informed consent to participate in the study. [Note: If the subject is under 18 years of age or is otherwise unable to legally give his or her informed consent to participate in the study, then written informed consent to participate must be obtained from the parent(s) or legal guardian(s) of the subject or other legal personal representative(s), as applicable. In addition, in the case of minor subjects, the written assent of the subject to participate in the study should be obtained where required by applicable institutional policy on the consenting of minor study participants.]
7. Willing and able to participate in all required study activities for the entire duration of the study (i.e., through completion of the posttreatment follow-up period). |
|
E.4 | Principal exclusion criteria |
1. If a female of reproductive potential, the subject is pregnant, planning to become pregnant during the anticipated duration of her participation in the study (i.e., through completion of the posttreatment follow-up period), or nursing a child.
2. Subjects with hypersensitivity (not including renal dysfunction or eye disorder) to CDV or to CMX001 or its formulation excipients.
3. Subjects who have received treatment with another investigational anti-EBOV medication or therapy (other than supportive care or transfusion with convalescent blood, plasma, or serum) unless prior approval has been received from the Chimerix medical monitor (or designee).
4. Subjects who are participating in another interventional clinical trial unless prior approval has been received from the Chimerix medical monitor (or designee).
5. Subjects who are receiving digoxin or ketoconazole (other than topical formulations) at Day 1 or who are anticipated to need treatment with either drug during the treatment phase of the study.
6. Subjects with end-stage renal disease, i.e., an estimated glomerular filtration rate (eGFR) < 15 mL/min, unless receiving renal replacement therapy (RRT).
7. Any other condition, including abnormal laboratory values, that would, in the judgment of the investigator, put the subject at increased risk by participating in the study, or would interfere with the conduct or planned analyses of the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the incidence of all-cause mortality through Day 29 (i.e., 28 days post-initiation of CMX001 therapy). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be evaluated through Day 29. |
|
E.5.2 | Secondary end point(s) |
Time to all-cause mortality through Day 29 ? Incidence of and time to all-cause mortality through Day 15 (i.e., 14 days post-initiation of CMX001 therapy)
? Number and percentage of subjects who achieve a sustained (confirmed) clearance of blood EBOV RNA by PCR. For the purposes of this protocol, a sustained (confirmed) clearance of blood EBOV RNA is defined as two consecutive undetectable PCR results at least three days apart.
? Time to clear EBOV RNA by PCR from all body compartments (e.g., blood, stool)
? Correlation between virologic response and subject survival
? Correlation between time from onset of symptoms and survival
? Correlation between clinical symptoms at first dose (e.g., presence or absence of diarrhea) and survival
? Emergence of viral resistance
Additional Safety Endpoints include:
? Incidence of treatment-emergent adverse events (TEAEs), in particular TEAEs of ? Grade 3 severity, as defined by the NIH/NCI CTCAE
? Incidence and severity of treatment-related TEAEs
? Incidence of SAEs
? Incidence of TEAEs leading to CMX001 dose interruption
? Incidence of permanent discontinuation from CMX001 due to TEAEs
Additional PK Endpoints include:
? Plasma concentrations of CMX001 and CDV
? Plasma PK parameters for CMX001 and CDV following first dose administration |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time to all-cause mortality through Day 29. Incidence of and time to all-cause mortality through Day 15. |
|
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 | 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.8.3 |
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 | 9 |
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 |
Belgium |
Canada |
France |
Germany |
Netherlands |
Norway |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
|
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
|
Last Visit of the Lase Subject (LVLS) |
|
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 | |
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 |