E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Human Immunodeficiency Virus (HIV) infection in patients with raltegravir (RAL) or elvitegravir (ELV) resistance who
have limited treatment options. |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of Human Immunodeficiency Virus (HIV) infection in patients |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020194 |
E.1.2 | Term | HIV-2 infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 100000004862 |
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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 |
The primary objective is to provide access in an open-label protocol program to patients who have documented RAL or ELV resistance, who have limited treatment options and who require DTG to construct a viable antiretroviral (ARV) regimen for therapy.
Eligible patients are those who are unable to participate in the Phase III/b DTG studies.
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess any serious adverse events (SAEs) and any adverse events (AEs) that lead to the discontinuation of DTG 50 mg twice daily (BID). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female patients aged ≥12 years weighing >40kg
NOTE: all female patients of child-bearing potential should use every precaution to prevent pregnancy. Contraception guidelines include:
• Complete abstinence from intercourse from 2 weeks prior to administration of DTG, throughout receipt of DTG, and for at least 2 weeks after discontinuation of DTG;
• Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
• Approved hormonal contraception;
• Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion);
• Male partner sterilization prior to the female patient’s entry into the study, and this male is the sole partner for that patient;
• Any other method with published data showing that the expected failure rate is <1% per year.
Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of IP.
All patients participating in the study should be counseled on the practice of safer sexual practices including the use of effective barrier methods (e.g., male condom/spermicide).
• Documented plasma HIV-1 RNA levels ≥400 copies/mL within 3 months prior to the Screening visit.Documented RAL or ELV resistance in the patient’s medical records (evidence of phenotypic and/or genotypic resistance must be provided to qualify for the EAP program). If resistance is not documented, Investigators may, at their own expense, test potential recruits.
• Inability to construct a viable background regimen of ART with commercially available medications.
• The patient/legal guardian or representative has given written informed consent to treatment prior to any program-specific assessments are initiated in accordance with country-specific regulatory authority requirements.
• For patients enrolled in France: a patient will be eligible for inclusion in this study only if, either affiliated to or, a beneficiary of a social security category. |
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E.4 | Principal exclusion criteria |
Deviations from exclusion criteria are not allowed because they can potentially jeopardize patient safety. Therefore, adherence to the criteria as specified in the protocol is essential.
Patients meeting any of the following criteria must not be enrolled in the program:
1. Patient has estimated creatinine clearance (CrCl) <30 mL/min via Cockcroft-Gault method [Cockcroft, 1976].
Calculated CrCl (mL/min) = (140 − age [years]) x weight (kg)/ [72 × serum creatinine (mg/100mL)]
Female patients: multiply by 0.85
In order to use SI units, the following formula may be used:
Calculated CrCl (mL/min) = (140 − age [years]) x weight (kg) x 1.23/serum creatinine (μmol/L)
Female patients: multiply by 0.85
2. Females who are pregnant or breastfeeding.
3. Patients who have had a known or suspected allergic reaction to an INI.
4. Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN) within 1 month of treatment initiation and/or at last ALT determination.
5. ALT >3 times ULN and total bilirubin >1.5 times ULN (with >35% direct bilirubin within 1 month of treatment initiation) and/or at last ALT and bilirubin determinations.
6. Evidence for severe hepatic impairment (Child-Pugh class C).
7. Patients who are eligible for, and have access to, an actively enrolling DTG Phase III/b clinical trial.
8. Any condition (including but not limited to alcohol and drug use) or any active clinically significant disease or findings during Screening of medical history or physical examination, which, in the opinion of the Investigator would interfere with patient safety or compliance.
9. Patient requires or is anticipated to require any of the prohibited concomitant therapy as listed in Section 5.6.2.
• French patients recruited at sites in France will be excluded if the patient has participated in any study using an investigational drug during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to Screening for the study, or the patient will participate simultaneously in another clinical trial.
NOTE: Patients should not be considered for the EAP if they are eligible and able to participate in any of the clinical treatment trials of DTG in treatment-experienced patients (protocols ING111762, ING112961 or ING112574). Please refer to any national or local requirements for participation in EAPs. In that instance (assuming consent is obtained), the patient should preferentially be enrolled into the ongoing clinical trial to allow detailed data collection.
Physicians with patients who do not fit all criteria cited above yet have a significant unmet medical need may appeal to the ViiV Safety and Labelling Committee in order to secure access to DTG under this program.
Notwithstanding these minimum inclusion and exclusion criteria, Investigators must also follow country specific guidelines where they exist when making decisions about patients who are eligible for study participation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
This is an open-label, expanded access study. No formal hypotheses testing will be performed. Data will provide only descriptive information on safety. |
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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) |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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
| 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 200 |
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 |
Austria |
Belgium |
Brazil |
Canada |
France |
Germany |
Greece |
Ireland |
Israel |
Italy |
Netherlands |
Norway |
Poland |
Portugal |
Romania |
Spain |
Switzerland |
United Kingdom |
United States |
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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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Participation of a patient in ING114916 will end when DTG receives local (by country) regulatory approval unless the study is terminated early. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |