Ph 2B/3 Tafenoquine (TFQ) Study in Prevention of Vivax Relapse

NCT01376167 | Completed Phase 2 Results

• 2 other identifiers: 112582TAF112582
• Study Type: interventional
• Target: 851
• Locations: 8 countries
• Sites: 14

Brief Summary

The purpose of this two part study is to test the safety and efficacy of Tafenoquine (with Cholorquine) as a radical cure for Plasmodium vivax (P.vivax) malaria relative to the control Chloroquine.Part 1 aims to select an efficacious and well tolerated dose that can be co-administered with Chloroquine. Part 2 will investigate the safety and efficacy of the selected dose (300 mg tafenoquine) in the treatment and radical cure of Plasmodium Vivax Malaria.

Conditions

Malaria, Vivax

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Recurrence-free Efficacy at 6 Months Post Dose

  A participant was considered to have demonstrated recurrence-free efficacy at 6 months if: a) Participant had non-zero P vivax asexual parasite count at Baseline. b) Participant showed initial clearance of P vivax parasitemia defined as two negative asexual P vivax parasite counts, with at least 6 hours between the counts, and no positive counts in the interval. c) Participant had no positive asexual P vivax parasite count at any assessment prior to or on Study Day 201 following initial parasite clearance. d) Participant did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment. e) Participant is parasite-free at 6 months. Participants were censored if they did not have P.vivax at Baseline, or took a drug with anti-malarial action despite not having malaria parasites, or did not have a 6 month assessment. The number of participants with recurrence-free efficacy at 6 months has been summarized.

  6 months post dose

Secondary Outcomes (23)

• Number of Participants With Recurrence-free Efficacy at 4 Months Post Dose

  4 months post dose

• Time to Recurrence of P Vivax Malaria

  Up to Day 180

• Time to Parasite Clearance

  Up to Day 180

• Time to Fever Clearance

  Up to Day 180

• Number of Participants With Hemoglobin Decline From Baseline Over First 29 Days

  Baseline and up to Day 29

Study Arms (9)

Tafenoquine 50mg

EXPERIMENTAL

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 50mg Tafenoquine will be administered on either Day 1 or Day2 depending on when eligibility is confirmed.

Drug: Chloroquine 600mg; Drug: Chloroquine 300mg; Drug: Tafenoquine 50mg

Tafenoquine 100mg

EXPERIMENTAL

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 100mg Tafenoquine will be administered on either Day 1 or Day2 depending on when eligibility is confirmed.

Drug: Chloroquine 600mg; Drug: Chloroquine 300mg; Drug: Tafenoquine 100mg

Tafenoquine 300mg

EXPERIMENTAL

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 300mg Tafenoquine will be administered on either Day 1 or Day2 depending on when eligibility is confirmed.

Drug: Chloroquine 600mg; Drug: Chloroquine 300mg; Drug: Tafenoquine 300mg

Tafenoquine 600mg

EXPERIMENTAL

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 600mg Tafenoquine will be administered on either Day 1 or Day2 depending on when eligibility is confirmed.

Drug: Chloroquine 600mg; Drug: Chloroquine 300mg; Drug: Tafenoquine 600mg

Primaquine 15mg

ACTIVE COMPARATOR

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 15mg Primaquine once daily Days 2-15.

Drug: Chloroquine 600mg; Drug: Chloroquine 300mg; Drug: Primaquine 15mg

Chloroquine only

PLACEBO COMPARATOR

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered.

Drug: Chloroquine 600mg; Drug: Chloroquine 300mg

Tafenoquine 300mg (Part 2)

EXPERIMENTAL

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 300mg Tafenoquine will be administered on either Day 1 or Day2 depending on when eligibility is confirmed.

Drug: Chloroquine 600mg (Part 2 ); Drug: Chloroquine 300mg (Part 2 ); Drug: Tafenoquine 300mg (Part 2)

Primaquine 15mg (Part 2)

ACTIVE COMPARATOR

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 15mg Primaquine once daily Days 2-15

Drug: Chloroquine 600mg (Part 2 ); Drug: Chloroquine 300mg (Part 2 ); Drug: Primaquine 15mg (Part2 )

Chloroquine only (Part 2)

PLACEBO COMPARATOR

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered

Drug: Chloroquine 600mg (Part 2 ); Drug: Chloroquine 300mg (Part 2 )

Interventions

Chloroquine 600mg DRUG

600mg Chloroquine given to each subject on Day 1 and Day2 of the trial

Chloroquine only; Primaquine 15mg; Tafenoquine 100mg; Tafenoquine 300mg; Tafenoquine 50mg; Tafenoquine 600mg

Chloroquine 300mg DRUG

300mg Chloroquine given to each subject on Day 3 of the trial

Chloroquine only; Primaquine 15mg; Tafenoquine 100mg; Tafenoquine 300mg; Tafenoquine 50mg; Tafenoquine 600mg

Tafenoquine 50mg DRUG

single dose 50mg Tafenoquine given to subject on treatment arm 1 on Days 1 or 2

Tafenoquine 50mg

Tafenoquine 100mg DRUG

single dose 100mg Tafenoquine given to subject on treatment arm 2 on Days 1 or 2

Tafenoquine 100mg

Tafenoquine 300mg DRUG

single dose 300mg Tafenoquine given to subject on treatment arm 3 on Days 1 or 2

Tafenoquine 300mg

Tafenoquine 600mg DRUG

single dose 600mg Tafenoquine given to subject on treatment arm 4 on Days 1 or 2

Tafenoquine 600mg

Primaquine 15mg DRUG

15mg Primaquine given once daily to subject on treatment arm 5 on Days 2 to 15.

Primaquine 15mg

Chloroquine 600mg (Part 2 ) DRUG

600mg Chloroquine given to each subject on Day 1 and Day2 of the trial.

Chloroquine only (Part 2); Primaquine 15mg (Part 2); Tafenoquine 300mg (Part 2)

Chloroquine 300mg (Part 2 ) DRUG

300mg Chloroquine given to each subject on Day 3 of the trial.

Chloroquine only (Part 2); Primaquine 15mg (Part 2); Tafenoquine 300mg (Part 2)

Tafenoquine 300mg (Part 2) DRUG

single dose 300mg Tafenoquine given to subject on treatment arm 3 on Days 1 or 2.

Tafenoquine 300mg (Part 2)

Primaquine 15mg (Part2 ) DRUG

15mg Primaquine given once daily to subject on treatment arm 3 on Days 2 to 15.

Primaquine 15mg (Part 2)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Parasite density \>100 and \<200,000/μL
• ≥16 years
• A female is eligible if she is non-pregnant, nonlactating and if she is of: - non-child bearing potential defined as: post-menopausal (12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone \>40 mIU/mL), pre-menopausal and has had a hysterectomy or a bilateral oophorectomy (removal of the ovaries) or a bilateral tubal ligation with medical report verification, negative pregnancy test or,
• child-bearing potential, has a negative serum pregnancy test at screening, and agrees to comply with one of the following during the treatment stage of the study and for a period of 90 days after stopping study drug:
• Use of oral contraceptive, either combined or progestogen alone used in conjunction with double barrier method as defined below
• Use of an intrauterine device with a documented failure rate of \<1% per year
• Use of depo provera injection (part 2)
• Double barrier method consisting of spermicide with either condom or diaphragm
• Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female.
• Complete abstinence from intercourse for 2 weeks prior to administration of study drug, throughout the study and for a period of 90 days after stopping study drug.
• A signed and dated informed consent is obtained from the subject or the subject's legal representative prior to screening.
• NB Assent is obtained from subjects \<18 years, where applicable and written or oral witnessed consent has been obtained from parent or guardian.
• The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned.
• Willing to be hospitalized for 3 days and return to clinic for all follow-up visits including Day 180

You may not qualify if:

• Severe vivax malaria as defined by World Health Organisation criteria.
• Severe vomiting (no food or inability to take food during previous 8 hours)
• Screening haemoglobin concentration \<7 g/dL.
• Glucose 6-phosphate dehydrogenase deficiency, assessed by a quantitative spectrophotometric phenotype assay:
• Part 1 - Males: Any subject with an enzyme level \<70% of the site median value for Glucose 6-phosphate dehydrogenase normals will be excluded. Females: Those females with a screening Hb ≥ 10 g/dL will only be excluded if their enzyme level is \<70% of the site median value for Glucose 6-Phosphate dehydrogenase normals. hose females with Hb ≥7 but \< 10 g/dL will be excluded if an enzyme level is not \> 90% of the site median value for Glucose 6-Phosphate dehydrogenase normals.
• Part 2 - Any subject with enzyme level \<70% of the site median value for Glucose 6-phosphate dehydrogenase normals will be excluded
• Liver function test alanine transaminase \>2x Upper Limit of Normal
• Any clinically significant concurrent illness (e.g. pneumonia, septicaemia), pre-existing conditions (e.g. renal disease, malignancy), conditions that may affect absorption of study medication (e.g. vomiting or severe diarrhea) or clinical signs and symptoms of severe cardiovascular disease (e.g. uncontrolled congestive heart failure or severe coronary artery disease). These abnormalities may be identified on the screening history and physical or laboratory examination.
• Subject has taken antimalarials (e.g. ACT, mefloquine, primaquine, chloroquine) or drugs with anti-malarial activity within the past 30 days by history.
• History of allergy to chloroquine, mefloquine, tafenoquine, primaquine or to any other 4- or 8-aminoquinolines.
• Any contraindications to chloroquine or primaquine administration including a history of porphyria, psoriasis or epilepsy (please refer to chloroquine and primaquine locally approved prescribing information).
• Subject who has previously received study medication for this protocol (all parts) or has received treatment with any other investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
• History of illicit drug abuse or heavy alcohol intake within 6 months of the study.
• Subjects who have taken or will likely require the use of medications from the prohibited medication list which include the following classes: Histamine-2 blockers and antacids.
• Drugs with haemolytic potential.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Medicines for Malaria Venture: collaborator

Study Sites (14)

GSK Investigational Site

Bāndarban, Bangladesh

Location

GSK Investigational Site

Manaus, Amazonas, 69040-000, Brazil

Location

GSK Investigational Site

Porto Velho, Rondônia, 76812-329, Brazil

Location

GSK Investigational Site

Oddar Meancheay Province, Cambodia

Location

GSK Investigational Site

Gonder, Ethiopia

Location

GSK Investigational Site

Jimma, Ethiopia

Location

GSK Investigational Site

Bikaner, India

Location

GSK Investigational Site

Chennai, 600016, India

Location

GSK Investigational Site

Lucknow, 226003, India

Location

GSK Investigational Site

Secunderabad, 500 003, India

Location

GSK Investigational Site

Iquitos, Loreto, Iqui 01, Peru

Location

GSK Investigational Site

Rio Tuba, Bataraza, 5306, Philippines

Location

GSK Investigational Site

Bangkok, 10400, Thailand

Location

GSK Investigational Site

Tak, 63110, Thailand

Location

Related Publications (5)

• Lacerda MVG, Llanos-Cuentas A, Krudsood S, Lon C, Saunders DL, Mohammed R, Yilma D, Batista Pereira D, Espino FEJ, Mia RZ, Chuquiyauri R, Val F, Casapia M, Monteiro WM, Brito MAM, Costa MRF, Buathong N, Noedl H, Diro E, Getie S, Wubie KM, Abdissa A, Zeynudin A, Abebe C, Tada MS, Brand F, Beck HP, Angus B, Duparc S, Kleim JP, Kellam LM, Rousell VM, Jones SW, Hardaker E, Mohamed K, Clover DD, Fletcher K, Breton JJ, Ugwuegbulam CO, Green JA, Koh GCKW. Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria. N Engl J Med. 2019 Jan 17;380(3):215-228. doi: 10.1056/NEJMoa1710775.

  PMID: 30650322 DERIVED

• Roper DR, De la Salle B, Soni V, Fletcher K, Green JA. Abrogation of red blood cell G6PD enzyme activity through Heat treatment: development of survey material for the UK NEQAS G6PD scheme. Int J Lab Hematol. 2017 Jun;39(3):308-316. doi: 10.1111/ijlh.12627. Epub 2017 Mar 20.

  PMID: 28318100 DERIVED

• Beck HP, Wampfler R, Carter N, Koh G, Osorio L, Rueangweerayut R, Krudsood S, Lacerda MV, Llanos-Cuentas A, Duparc S, Rubio JP, Green JA. Estimation of the Antirelapse Efficacy of Tafenoquine, Using Plasmodium vivax Genotyping. J Infect Dis. 2016 Mar 1;213(5):794-9. doi: 10.1093/infdis/jiv508. Epub 2015 Oct 23.

  PMID: 26500351 DERIVED

• Tenero D, Green JA, Goyal N. Exposure-Response Analyses for Tafenoquine after Administration to Patients with Plasmodium vivax Malaria. Antimicrob Agents Chemother. 2015 Oct;59(10):6188-94. doi: 10.1128/AAC.00718-15. Epub 2015 Jul 27.

  PMID: 26248362 DERIVED

• Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, Krudsood S, Gupta SK, Kochar SK, Arthur P, Chuenchom N, Mohrle JJ, Duparc S, Ugwuegbulam C, Kleim JP, Carter N, Green JA, Kellam L. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study. Lancet. 2014 Mar 22;383(9922):1049-58. doi: 10.1016/S0140-6736(13)62568-4. Epub 2013 Dec 19.

  PMID: 24360369 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Malaria, Vivax

Interventions

Chloroquine; tafenoquine; Primaquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 20, 2011
• Study Start: April 24, 2014
• Primary Completion: November 18, 2016
• Study Completion: November 18, 2016
• Last Updated: April 23, 2018
• Results First Posted: April 23, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will share

Locations

PH (1); ET (2); TH (2); BR (2); IN (4); PE (1); BA (1); CA (1)