Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dolutegravir Study in HIV-1 Participants Completing IMPAACT Studies P1093 and P2019

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.
 
ClinicalTrials.gov Identifier: NCT03016533
Recruitment Status : Recruiting
First Posted : January 10, 2017
Last Update Posted : September 7, 2020
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

Tracking Information
First Submitted Date  ICMJE January 6, 2017
First Posted Date  ICMJE January 10, 2017
Last Update Posted Date September 7, 2020
Actual Study Start Date  ICMJE June 7, 2017
Estimated Primary Completion Date December 29, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2020)
Number of participants with continued access to age appropriate formulation of dolutegravir [ Time Frame: Up to 4 years ]
To provide access to age appropriate formulation of investigational product (dolutegravir), either as Tivicay or as fixed dose combination ABC/DTG/3TC in an open-label protocol to eligible participants who have completed P1093 and P2019 studies respectively.
Original Primary Outcome Measures  ICMJE
 (submitted: January 6, 2017)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2020)
  • Number of participants with serious adverse events (SAEs) as a measure of safety [ Time Frame: Up to 2 years ]
    An SAE is defined as any untoward medical occurrence that, at any dose: 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.
  • Number of participants with SAEs based on the severity [ Time Frame: Up to 2 years ]
    An SAE is defined as any untoward medical occurrence that, at any dose: 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. The Division of acquired immunodeficiency syndrome (DAIDS) table for grading the severity of adult and pediatric adverse events will be used to assess severity.
  • Number of participants with any clinical or laboratory adverse events leading to discontinuation of investigational product [ Time Frame: Up to 2 years ]
    An adverse event 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 investigational product.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2017)
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dolutegravir Study in HIV-1 Participants Completing IMPAACT Studies P1093 and P2019
Official Title  ICMJE Open-label Access to Dolutegravir for HIV-1 Infected Children and Adolescents Completing IMPAACT Studies P1093 and P2019
Brief Summary Dolutegravir is a potent integrase strand transfer inhibitor. Abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) is a fixed dose combination regimen containing two nucleoside reverse transcriptase inhibitors and dolutegravir. This is a phase 3b, non-randomized, open-label, multi-center, two treatment rollover study. The primary objective of this pediatric interventional study is to provide continued access to age appropriate formulations of investigational product (dolutegravir), either as Tivicay or as part of fixed dose combination ABC/DTG/3TC, for eligible participants who previously participated in parent studies P1093 (NCT01302847) or P2019 (NCT03760458) and who cannot locally access age appropriate formulations of dolutegravir or ABC/DTG/3TC in the public sector. The P1093 study was designed to evaluate the pharmacokinetics (PK), safety, tolerability and antiviral activity of dolutegravir in combination with optimized background regimens in human immunodeficiency virus type 1 (HIV-1) experienced adolescents and children as well as treatment naïve infants and toddlers. The P2019 study was designed to evaluate PK, safety, tolerability and antiviral activity of ABC/DTG/3TC dispersible and immediate release tablets in HIV-1-infected children. Participants who have tolerated investigational product in the parent studies without any significant toxicity or signs of virologic failure leading to the permanent discontinuation of investigational product and withdrawal from the parent study will be considered for this open label continued access study. Participants will receive their age/weight appropriate dose of investigational product as defined in the parent study. The duration of participation in the study will extend until age appropriate formulations of Tivicay or ABC/DTG/3TC receive local (by country) regulatory approval and are available in those countries from another source (e.g. government programs, aid programs, assistance programs, etc.) or the participant is no longer deriving benefit from treatment or meets a protocol defined reason for discontinuation. Participants will be enrolled after all screening procedures have been completed. In most cases, the Screening visit will overlap with the participants penultimate visit on the parent study (at Week 180 of P1093, or Week 36 of the P2019 study). 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 investigational product. It is estimated that no more than 300 participants will be enrolled in this study. Tivicay is a registered trademark of ViiV Healthcare.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • 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.
  • Drug: ABC/DTG/3TC immediate release tablets
    ABC/DTG/3TC immediate release tablets will be provided as biconvex, oval tablets containing 600 mg ABC, 50 mg DTG and 300 mg 3TC.
  • Drug: ABC/DTG/3TC film-coated dispersible tablets
    ABC/DTG/3TC dispersible tablets will be provided as biconvex, oval, film-coated tablets containing 60 mg ABC, 5 mg DTG and 30 mg 3TC.
Study Arms  ICMJE
  • Experimental: Dolutegravir (Tivicay)
    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 milligram (mg), 25 mg and 50 mg; 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 is discontinued, or until development of dolutegravir is terminated. The dose adjustment will be made if a participant's weight change requires a dose adjustment.
    Interventions:
    • Drug: Dolutegravir film-coated tablets
    • Drug: Dolutegravir film-coated dispersible tablets
  • Experimental: ABC/DTG/3TC
    All participants will receive ABC/DTG/3TC immediate release tablets or film-coated dispersible tablets at appropriate doses selected as per their weight bands. For those participants who were previously receiving ABC/DTG/3TC in study P2019 (parent study), ABC/DTG/3TC will be supplied as immediate release tablets containing 600 mg, 50 mg and 300 mg of ABC, DTG, and 3TC respectively and film-coated dispersible tablets containing 60 mg, 5 mg and 30 mg of ABC, DTG, and 3TC respectively. Participants will receive ABC/DTG/3TC until age-appropriate formulations are available to them from some other source, until participant is no longer deriving benefit from treatment, or until participant is discontinued, or until development of ABC/DTG/3TC is terminated. The dose adjustment will be made if a participant's weight change requires a dose adjustment.
    Interventions:
    • Drug: ABC/DTG/3TC immediate release tablets
    • Drug: ABC/DTG/3TC film-coated dispersible tablets
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 24, 2019)
300
Original Estimated Enrollment  ICMJE
 (submitted: January 6, 2017)
40
Estimated Study Completion Date  ICMJE December 29, 2023
Estimated Primary Completion Date December 29, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant must have completed participation in one of the following parent studies, for the duration noted, with continued benefit from investigational product: a. P1093 parent study through at least Week 180; b. P2019 parent study through at least Week 48. Participant with evidence of Virological Failure in either parent study must have eligibility for this rollover study discussed and agreed with the ViiV Healthcare Medical Monitor.
  • Virological control: a. Participants in parent study P1093 must have virological control defined as HIV-1 ribonucleic acid (RNA) <400 copies per milliliter (c/mL) at their penultimate visit (on or after the Week 180 visit); b. Participants in parent study P2019 must have virological control defined as HIV-1 RNA <200 c/mL at their penultimate visit (on or after Week 36).
  • Males and Females: All participants who are engaging in sexual activity should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (example [e.g.] male condom) and on the risk of HIV transmission to an uninfected partner. Females: Female participants who are of child bearing potential and who are engaging in sexual activity that could lead to pregnancy, must agree to use one of the acceptable birth control methods until the last dose of study medication and completion of the follow-up visit (4 weeks after the last dose). Condoms are recommended in addition, because their appropriate use is the only contraception method effective for preventing HIV-1 transmission.
  • Parent or legal guardian or participant >=18 years of age is able and willing to provide signed informed consent.

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], alanine aminotransferase [ALT], lipase, serum creatinine and total bilirubin). Repeat testing is allowed for eligibility determination.
  • Previous permanent discontinuation from investigational product in the parent study due to toxicity, intolerance or pregnancy.
  • ALT >=5 times the upper limit of normal (ULN), or ALT >=3 times ULN and bilirubin >=1.5 times ULN (with >35 percent [%] direct bilirubin) within 30 days prior to study entry. Participants with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification should be excluded.
  • Estimated glomerular filtration rate (eGFR) bedside Schwartz formula; <60 milliliter per minute per 1.73 square meter within 30 days prior to study entry.
  • Participants positive for hepatitis B virus in the parent study (hepatitis B virus surface antigen positive).
  • Female who are pregnant or plan to become pregnant or breastfeed during the study.
  • Participant 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.
  • Participants transitioning from the P2019 study (taking ABC/DTG/3TC) must be Human Leukocyte Antigen-B*5701-negative based on documented testing at any time prior to entry.
  • Use of any disallowed medications at time of Screening.
  • Anticipated need for Hepatitis C virus therapy with interferon or any drugs that have potential for adverse drug: drug interactions with study treatment throughout the entire study period.
  • Participant 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 participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE Botswana,   Brazil,   South Africa,   Tanzania,   Thailand,   United States,   Zimbabwe
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03016533
Other Study ID Numbers  ICMJE 205858
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party ViiV Healthcare
Study Sponsor  ICMJE ViiV Healthcare
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials ViiV Healthcare
PRS Account ViiV Healthcare
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP