Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine or Chloroquine/Azithromycin Prophylaxis

NCT01783340 | Withdrawn Phase 1 DMC

• 2 other identifiers: MMVNL42517.000.12
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the superior protective immunity of the combination of chloroquine and azithromycin prophylaxis under Chemoprophylaxis Sporozoites (CPS) immunization versus a standard chloroquine prophylactic regimen.

Conditions

Malaria, Falciparum

Keywords

Malaria; P falciparum; Chloroquine; Azithromycin; Immunization

Outcome Measures

Primary Outcomes (1)

• Volunteers falciparum positive by thick smear

  Percentage of P. falciparum thick smear negative volunteers on day 21 (protection against challenge infection)

  One year

Secondary Outcomes (4)

• Duration of pre-patent period by thick smear

  One year

• Kinetics of parasitemia by PCR

  One year

• Adverse events

  One year

• Immune responses

  One year

Study Arms (3)

CQ and falciparum immunization

ACTIVE COMPARATOR

This arm will receive chloroquine prophylaxis, a placebo during immunizations and three times 5 infected mosquito-bites (immunizations). Standard Chloroquine prophylactic regime: a loading dose of 300 mg on day 1 and day 3 and then 300 mg once a week, starting on day 7, for a total duration of 13 weeks. Placebo capsules daily on three consecutive days starting on each of three immunization days. Challenge: Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes. When thick smear positive, of at day 21 after challenge, a standard 3 day treatment of Malarone will be given.

Drug: Placebo; Biological: Immunization with falciparum

CQ/AZM and falciparum immunization

EXPERIMENTAL

This arm will receive chloroquine and azithromycin prophylaxis and three times 5 infected mosquito-bites (immunizations). Standard Chloroquine prophylactic regime: a loading dose of 300 mg on day 1 and day 3 and then 300 mg once a week, starting on day 7, for a total duration of 13 weeks. Azithromycin capsules 1000mg daily on three consecutive days starting on each of three immunization days. Challenge: Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes. When thick smear positive, of at day 21 after challenge, a standard 3 day treatment of Malarone will be given.

Drug: Azithromycin capsules; Biological: Immunization with falciparum

CQ and AZM control

PLACEBO COMPARATOR

This arm will receive chloroquine and azithromycin prophylaxis and three times 5 uninfected mosquito-bites during immunization. Standard Chloroquine prophylactic regime: a loading dose of 300 mg on day 1 and day 3 and then 300 mg once a week, starting on day 7, for a total duration of 13 weeks. Azithromycin capsules 1000mg daily on three consecutive days starting on each of three immunization days. Challenge: Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes. When thick smear positive, of at day 21 after challenge, a standard 3 day treatment of Malarone will be given.

Drug: Azithromycin capsules

Interventions

Azithromycin capsules DRUG

Azithromycin capsules will be administered at each immunization

Also known as: Zithromax

CQ and AZM control; CQ/AZM and falciparum immunization

Placebo DRUG

Placebo capsules will be administered at each immunization

CQ and falciparum immunization

Immunization with falciparum BIOLOGICAL

three inoculations with 5 infected mosquito bites

CQ and falciparum immunization; CQ/AZM and falciparum immunization

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥ 18 and ≤ 35 years healthy volunteers (males or females)
• Good health based on history and clinical examination
• Negative pregnancy serum test
• For females who are sexually active: use of adequate contraception (incl. condom use)
• Signing of the informed consent form, thereby demonstrating understanding of the meaning and procedures of the study
• Agreement to inform the general practitioner and to sign a request to release medical information concerning contra-indications for participation in the study
• Willingness to undergo a Pf controlled infection through mosquito bites
• Agreement to stay in a hotel room close to the trial centre during a part of the study (Day 7 till day 15 after challenge)
• Reachable (24/7) by mobile phone during the whole study period
• Available to attend all study visits
• Agreement to refrain from blood donation or for other purposes, during the whole study period
• Willingness to undergo HIV, hepatitis B and hepatitis C tests
• Negative urine toxicology screening test at screening visit and the day before challenge
• Willingness to take a prophylactic regime of chloroquine or chloroquine/azithromycin combination and a curative regimen of Malarone® after challenge.

You may not qualify if:

• History of malaria
• Plans to travel to malaria endemic areas during the study period
• Plans to travel outside of the Netherlands during the challenge period
• History of stay in malaria endemic areas for more than 6 months
• Previous participation in any malaria vaccine study and/or positive serology for Pf
• Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, and other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteer
• History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)
• History of arrhythmias or prolonged QT-interval
• Positive family history in 1st and 2nd degree relatives for cardiac events \< 50 years old
• An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system
• Clinically significant abnormalities in electrocardiogram (ECG) at screening
• Body Mass Index (BMI) below 18 or above 30 kg/m2
• Any clinically significant deviation from the normal range in biochemistry or haematology blood tests or in urine analysis
• Positive HIV, HBV or HCV tests
• Participation in any other clinical study within 30 days prior to the onset of the study

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Leiden University Medical Center: collaborator
• Medicines for Malaria Venture: collaborator

Study Sites (1)

Leiden University Medical Centre

Leiden, Leiden, 2333ZA, Netherlands

Location

Related Publications (1)

• Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Roeffen W, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009 Jul 30;361(5):468-77. doi: 10.1056/NEJMoa0805832.

  PMID: 19641203 RESULT

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

Azithromycin; Immunization

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Primary Prevention; Preventive Health Services; Health Services; Health Care Facilities Workforce and Services; Communicable Disease Control; Public Health Practice; Public Health; Environment and Public Health

Study Officials

• RW Sauerwein, MD PhD

  Radboud University Medical Center

  STUDY DIRECTOR

• LG Visser, MD PhD

  Leiden University Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2013
• First Posted: February 4, 2013
• Study Start: April 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: April 1, 2014
• Last Updated: November 13, 2014

Record last verified: 2014-11

Locations

NL (1)