PH3b, DTG Study in HIV-1 Subjects Completing IMPAACT Study P1093

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03016533
Recruitment Status : Recruiting
First Posted : January 10, 2017
Last Update Posted : August 10, 2017
Information provided by (Responsible Party):
ViiV Healthcare

Brief Summary:
Dolutegravir (DTG) is a potent inhibitor of the human immunodeficiency virus type 1 (HIV-1) integrase that has been developed for the treatment of HIV. This is a phase 3b (PH3b), non-randomized, open-label, multi-center, treatment rollover study. The primary objective of this pediatric interventional study is to provide continued access to DTG for eligible participants who previously participated in the international maternal pediatric adolescent acquired immunodeficiency syndrome [AIDS] clinical trials (IMPAACT) P1093 study (parent study) and who cannot locally access DTG in the public sector. The P1093 study was designed to evaluate the pharmacokinetics (PK), safety, tolerability and antiviral activity of DTG in HIV-1 experienced adolescents and children as well as treatment-naive infants and toddlers. Participants who have no evidence of virological failure (VF) and who have tolerated DTG in the parent study without any significant toxicity leading to the permanent discontinuation of this drug and withdrawal from the parent study will be considered for this open-label continued access study. Participants will be receiving their age/weight appropriate dose of DTG as defined in the parent study. The objective of this study will be supported through evaluation of serious adverse events. The duration of participant accrual into the study will extend until DTG receives local (by country) regulatory approval . Therefore, participants enrolled into this study will be those who will benefit from treatment and will continue to receive DTG until local (by country) regulatory approval and commercial or other availability occurs from another source (e.g. government programs, aid programs, assistance programs, etc.). Participants will be enrolled after all screening procedures have been completed. In most cases, the Screening visit will overlap with the participant's penultimate visit on the parent study (at Week 180 of P1093). Participants who meet all entry criteria may enroll and will be seen in the clinic every 12 weeks for a safety evaluation and to receive DTG. It is estimated that no more than 120 participants will be enrolled in this study.

Condition or disease Intervention/treatment Phase
Infection, Human Immunodeficiency Virus Drug: Dolutegravir film-coated tablets Drug: Dolutegravir film-coated dispersible tablets Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label Access to Dolutegravir for HIV-1 Infected Children and Adolescents Completing IMPAACT Study P1093
Actual Study Start Date : June 7, 2017
Estimated Primary Completion Date : December 29, 2023
Estimated Study Completion Date : December 29, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Dolutegravir Continued Access
All participants will receive dolutegravir film-coated tablets or film-coated dispersible tablets at appropriate doses selected as per their age and weight bands. For those participants who were previously receiving dolutegravir in study P1093 (parent study), dolutegravir will be supplied as film-coated tablets containing 10 mg, 25 mg and 50 mg of dolutegravir and 5 mg film-coated dispersible tablets of dolutegravir. Participants will receive dolutegravir until age-appropriate formulations are available to them from some other source, or until participant is no longer deriving benefit from treatment, or participant are discontinued, or until development of dolutegravir is terminated. The dose adjustment will be made if a participant's weight change requires a dose adjustment. Aging participants (those who crosses age-boundaries) who are taking the dispersible tablet formulation will be allowed to switch to the tablet formulation once daily if they are able to swallow the tablet.
Drug: Dolutegravir film-coated tablets
Dolutegravir film-coated tablets will be provided as 10 mg, 25 mg and 50 mg tablets. It will be administered at the dose of approximately 1 mg/kilogram (kg) with maximum dose of 50 mg to participants as per their age and weight band.

Drug: Dolutegravir film-coated dispersible tablets
Dolutegravir film-coated dispersible tablets will be provided as 5 mg dispersible tablets. It will be administered at the appropriate dose as determined by results of the parent protocol to participants as per their age and weight band.

Primary Outcome Measures :
  1. Continued access to dolutegravir [ Time Frame: Assessed up to average of 2 years ]
    To provide access to dolutegravir in an open-label protocol to eligible participants who have completed the P1093 study.

Secondary Outcome Measures :
  1. Incidence and severity of serious adverse events (SAEs) as a measure of safety [ Time Frame: Assessed up to average of 2 years ]
    An SAE is defined as any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function.

  2. Number of participants with any clinical or laboratory adverse events leading to discontinuation of dolutegravir [ Time Frame: Assessed up to average of 2 years ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Between >=4 weeks and <18 years of age inclusive, at the Day 1 visit for the P1093 study.
  • Subjects must have previously participated in the P1093 study (parent study) through at least Week 180 with no evidence of VF.
  • Subjects must have virological control defined as HIV-1 ribonucleic acid (RNA) <400 copies per milliliter (c/mL) during the parent study at their penultimate P1093 visit (on or after the Week 180 visit). If the penultimate P1093 visit on or after the Week 180 visit indicates the possibility of VF, a retest can be used to confirm eligibility. Adherence issues should be addressed and viral suppression must be confirmed prior to Day 1.
  • Demonstrated ability or willingness to swallow assigned dolutegravir (DTG) tablets (for subjects requiring tablets). DTG 10, 25, and 50 milligram (mg) tablets may not be crushed or dissolved. The 5 mg dispersible tablets may not be cut and must be used in five milligram intervals.
  • Female subjects who are of child bearing potential and male subjects engaging in sexual activity should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g. male condom) and on the risk of HIV transmission to an uninfected partner. Male subjects engaging in sexual activity that could lead to HIV-1 transmission must use a condom. Female subjects who are of child bearing potential and who are engaging in sexual activity that could lead to pregnancy, must use 2 adequate birth control methods while on study and for 2 weeks after stopping study drug. Condoms are recommended in addition, because their appropriate use is the only contraception method effective for preventing HIV-1 transmission.
  • Parent, legal guardian or subject >=18 years of age is able and willing to provide signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

Exclusion Criteria:

  • Presence of any active AIDS defining opportunistic infection.
  • Known >=grade 3 laboratory toxicities prior to study entry (e.g. neutrophil count, hemoglobin, platelets, aspartate aminotransferase [AST], aspartate aminotransferase [ALT], lipase, serum creatinine and total bilirubin). Repeat testing will be allowed for eligibility determination. >=grade 3 total bilirubin is allowable, if the subject is on atazanavir (ATV). Subjects with laboratory abnormalities considered unrelated to DTG may be allowed to enter the study. Thus, if the laboratory abnormality persists upon repeat testing, the subject may be considered for study entry after consultation and approval of the study team.
  • Subjects who were permanently discontinued from DTG in the parent study due to intolerance or pregnancy must not be included in this current program.
  • The following liver toxicities within 30 days prior to study entry: ALT >3 times upper limit of normal (ULN) and direct bilirubin is >2 times ULN.
  • Women who are pregnant or plan to become pregnant or breastfeed during the study.
  • Subject is currently participating in or has participated in a study with a compound or device that is not commercially available within 30 days of signing informed consent, unless permission from the sponsor's medical monitor is granted.
  • Presence of any history of allergy/sensitivity to any of the study drugs.
  • Use of any disallowed medications at time of screening.
  • Subject is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.
  • Clinical or symptomatic evidence of pancreatitis, as determined by the clinician.
  • Any condition (including but not limited to alcohol and drug use) that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03016533

Contact: US GSK Clinical Trials Call Center 877-379-3718

GSK Investigational Site Recruiting
Chiang Mai, Thailand, 50200
Contact: US GSK Clinical Trials Call Center    877-379-3718   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466   
Sponsors and Collaborators
ViiV Healthcare
Study Director: GSK Clinical Trials ViiV Healthcare

Responsible Party: ViiV Healthcare Identifier: NCT03016533     History of Changes
Other Study ID Numbers: 205858
First Posted: January 10, 2017    Key Record Dates
Last Update Posted: August 10, 2017
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ViiV Healthcare:
Continued access study

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents