Assessing a Risk Model for G6PD Deficiency

NCT03337152 | Terminated Phase 4 Results DMC

• 1 other identifier: 856370-2
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

A clinical study designed to develop and inform an individual risk of hemolysis model based on individual red blood cell G6PD levels. Volunteers who are eligible to treatment with primaquine as per national guidelines and with confirmed normal G6PD levels as per the fluorescent spot test will be exposed to treatment regimens of either primaquine alone for 14 days or 3 day chloroquine with concomitant primaquine for 14 days. The volunteers will be followed intensively during treatment and for 14 days after treatment for haematologic measures, G6PD quantification, and drug level assays.

Conditions

Malaria, Vivax; G6PD Deficiency

Outcome Measures

Primary Outcomes (2)

• Change in Haemoglobin

  The change in haemoglobin from baseline on exposure to primaquine for P.vivax treatment over treatment course to hemoglobin level at day 28.

  28 days after enrollment

• Change in G6PD Concentration

  The haemoglobin-related change in G6PD concentration, as determined by spectrometer, over treatment course. Change is determined from baseline to day 28

  28 days after enrollment

Secondary Outcomes (5)

• Significance of CYP2D6

  28 days after enrollment

• Association of Drug Levels

  Days 1,2,3,5,7,9,11,14,17,21

• Serious Adverse Events

  28 days after enrollment

• Significance of Reticulocyte Count

  Days 1,2,3,5,7,9,11,14,17,21

• Significance of Urobilinogen Levels

  Days 1,2,3,5,7,9,11,14,17,21

Study Arms (2)

1A: primaquine

OTHER

Twelve males hemizygous for wildtype G6PD, 12 females homozygous for wildtype G6PD, and 12 females heterozygous for G6PD deficiency will be randomized to arm 1A. Participants in arm 1A will receive primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed.

Drug: primaquine

1B: chloroquine + primaquine

OTHER

Twelve males hemizygous for wildtype G6PD, 12 females homozygous for wildtype G6PD, and 12 females heterozygous for G6PD deficiency will be randomized to arm 1B. Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed.

Drug: chloroquine + primaquine

Interventions

primaquine DRUG

Participants receive primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed.

1A: primaquine

chloroquine + primaquine DRUG

Participants will receive chloroquine for 3 days concomitant with primaquine for 14 days at 0.5 mg/Kg. Drug administration will be directly observed.

1B: chloroquine + primaquine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previous G6PD test at Shoklo Malaria Research Unit (SMRU) clinic with one of following results: 1) G6PD homozygous wildtype females (G6PD genotype normal) 2) G6PD heterozygous females with a normal FST (G6PD genotype abnormal with G6PD activity ≥40% and ≤80% of normal ) 3) G6PD hemizygous wildtype males (G6PD genotype normal)
• Willing to participate and sign informed consent form
• Willing to allow donated samples to be used in future research
• Aged ≥18 years
• Ability (in the investigators' opinion) and willing to comply with all study requirements

You may not qualify if:

• All participants:
• Malaria or other illness
• Recent history (within 20 days) of anti-malarial treatment
• History of allergy or adverse reaction to chloroquine or primaquine
• Blood transfusion in the past 3 months
• G6PD activity less than 40% normal activity or 3.00 IU/gHb by the quantitative G6PD spectrophotometric assay
• Haemoglobin ≤10 g/dL
• Presence of any condition which in the judgment of the investigator would place the subject at undue risk or interfere with the results of the study
• Female participants only:
• Pregnancy at the time of screening
• Breastfeeding

Sponsors & Collaborators

• PATH: lead
• Mahidol Oxford Tropical Medicine Research Unit: collaborator

Study Sites (1)

Shoklo Malaria Research Unit (SMRU)

Mae Sot, Thailand

Location

MeSH Terms

Conditions

Malaria, Vivax; Glucosephosphate Dehydrogenase Deficiency

Interventions

Primaquine; Chloroquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The study met study halting rules and was terminated early. As a result, the full sample size was not enrolled and a complete data set was not available. Thus, the objectives of assessing and developing a G6PD risk model could not be met.

Results Point of Contact

• Title: Gonzalo Domingo
• Organization: PATH

gdomingo@path.org

206-285-3500

Study Officials

• François Nosten, MD, PhD

  Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized into one of two arms. 1a will receive primaquine for 14 days, and Arm 1b will receive chloroquine for 3 days and concomitant primaquine for 14 days.

Study Record Dates

• First Submitted: October 27, 2017
• First Posted: November 8, 2017
• Study Start: May 7, 2018
• Primary Completion: August 21, 2018
• Study Completion: October 21, 2018
• Last Updated: November 12, 2021
• Results First Posted: November 12, 2021

Record last verified: 2019-05

Locations

TH (1)