Controlled Human Malaria Infection (CHMI) After Immunization With Cryopreserved Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis

NCT01728701 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: TIP52012-000322-21
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine the safety and tolerability of ID administration of PfSPZ Challenge to volunteers taking chloroquine chemoprophylaxis (an approach called PfSPZ-CVac).

Conditions

Malaria; Plasmodium Falciparum

Keywords

Malaria; Plasmodium falciparum; PfSPZ Challenge; Chemoprophylaxis; PfSPZ-CVac

Outcome Measures

Primary Outcomes (1)

• Frequency and magnitude of adverse events in study groups

  Signs and symptoms will be recorded at all visits, and whenever a trial volunteer reports signs or symptoms to the trial physician between visits. The following signs and symptoms will be solicited: Fever, Headache, Malaise, Fatigue, Dizziness, Myalgia, Arthralgia, Nausea, Vomiting, Chills, Diarrhoea, Abdominal pain (Verhage 2005), Chest pain, Palpitations and Shortness of breath.

  All study visits+as reported by volunteer upto 53 weeks

Secondary Outcomes (3)

• Presence of parasitemia after Pf CHMI as assessed by microscopy

  Thick smears will be performed on all visits following immunizations and Pf CHMI until treatment is finished upto 53 weeks

• Time to parasitemia after Pf CHMI as assessed by microscopy

  Thick smears will be performed on all visits following immunizations and Pf CHMI until treatment is finished upto 53 weeks

• Kinetics of parasitemia as assessed by qPCR

  Samples collected on all visits following immunizations and Pf CHMI until treatment is finished upto 53 weeks

Other Outcomes (1)

• Immune responses in study groups: Cellular immune responses, Antibody production, Cytokine profile

  Baseline and throughout the period of study upto 53 weeks

Study Arms (4)

Grp 1: 75,000 PfSPZ Challenge, 3 immunizations

EXPERIMENTAL

Grp 1 (10 volunteers) receive std weekly chloroquine (CQ) chemoprophylaxis for 14 weeks(98 days). In this time, Grp 1 gets 6 ID injections of PfSPZ Challenge (total 75,000 PfSPZ NF54 strain), on days 8, 36 \& 64 (immunizations 1, 2 \& 3). 33 days after last dose of CQ, Grp 1 will have CHMI by bites of 5 mosquitoes infected with Pf NF54 strain.

Biological: PfSPZ Challenge

Grp 2: Normal Saline (NS)

PLACEBO COMPARATOR

Grp 2 (5 volunteers) receive std weekly chloroquine (CQ) chemoprophylaxis for 14 weeks(98 days). In this time, Grp 2 gets ID injections of normal saline, on days 8, 36 \& 64 (immunizations 1, 2 \& 3). 33 days after last dose of CQ, Grp 2 will have CHMI by bites of 5 mosquitoes infected with Pf NF54 strain.

Biological: Normal Saline (NS)

Grp 3: 75,000 PfSPZ Challenge, 3/4 immunizations

EXPERIMENTAL

Grp 3 (10 volunteers) receive std weekly chloroquine (CQ) chemoprophylaxis for 14 weeks(98 days). In this time, Grp 3 gets 6 ID injections of PfSPZ Challenge (total 75,000 PfSPZ NF54 strain), on days 8, 36 \& 64 (immunizations 1, 2 \& 3). Grp 3 outcome is dependent on results of Grp 1. If ≥75% of Grp 1 are protected against homologous Pf CHMI, Grp 3 will have CHMI by bites of 5 mosquitoes infected with heterologous Pf NF135.C10 strain 75 days after last dose of CQ. If \<75% of Grp 1 are protected against homologous Pf CHMI, Grp 3 will receive 1 additional immunization (immunization 4), consisting of 6 ID injections on the same day of 75,000 PfSPZ Challenge, at day 162. In this 4th immunization period CQ will be administered for another 6 weeks starting at day 154. Finally, 33 days after last dose of CQ, Grp 3 will have homologous Pf CHMI by bites of 5 PfSPZ-infected mosquitoes.

Biological: PfSPZ Challenge

Grp 4: Normal Saline (NS)

PLACEBO COMPARATOR

Grp 4 (5 volunteers) receive std weekly chloroquine (CQ) chemoprophylaxis for 14 wks(98 days). In this time, Grp 4 gets ID injections of NS, on days 8, 36 \& 64 (immunizations 1, 2 \& 3). Grp 4 outcome is dependent on results of Grp 1. If ≥75% of Grp 1 are protected against homologous Pf CHMI, Grp 4 will have CHMI by bites of 5 mosquitoes infected with heterologous Pf NF135.C10 strain 75 days after last dose of CQ. If \<75% of Grp 1 are protected against homologous Pf CHMI, Grp 4 will receive 1 additional immunization (immunization 4), consisting of ID injections of NS, at day 162. In this 4th immunization period CQ will be administered for another 6 weeks starting at day 154. Finally, 33 days after last dose of CQ, Grp 4 will have homologous Pf CHMI by bites of 5 PfSPZ-infected mosquitoes.

Biological: Normal Saline (NS)

Interventions

PfSPZ Challenge BIOLOGICAL

PfSPZ Challenge is a suspension of aseptic, purified, cryopreserved PfSPZ that are thawed and formulated in diluent on the day of administration.

Grp 1: 75,000 PfSPZ Challenge, 3 immunizations; Grp 3: 75,000 PfSPZ Challenge, 3/4 immunizations

Normal Saline (NS) BIOLOGICAL

Normal saline

Grp 2: Normal Saline (NS); Grp 4: Normal Saline (NS)

Eligibility Criteria

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

You may qualify if:

• Healthy volunteers (males or females) of ≥ 18 and ≤ 35 years of age
• Good health based on history and clinical examination (physical examination and laboratory screening)
• Negative pregnancy test
• Use of adequate contraception for females
• 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 contraindications for participation in the study
• Willingness to undergo administration of PfSPZ Challenge by needle and syringe and willingness to undergo challenge by mosquito bites
• For volunteers not living in Nijmegen: agreement to stay in a hotel room close to the trial centre or living in Nijmegen with a third party that could contact the clinicians in case of alteration of consciousness during a part of the study (day 5 after challenge until treatment is finished)
• Reachable (24/7) by mobile phone during the whole study period
• For volunteers living in Nijmegen: living with a third party that could contact the clinicians in case of alteration of consciousness or agreement to stay in a hotel room close to the trial centre during a part of the study (day 5 after challenge until treatment is finished)
• Available to attend all study visits
• Agreement to refrain from blood donation to Sanquin 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 and a curative regimen of Malarone®

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
• 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 volunteers
• History of diabetes mellitus or cancer (except basal cell carcinoma of the skin)
• History of arrhythmias or prolonged QT-interval
• Positive family history of 1st and/or 2nd degree relatives who experienced cardiac events when \< 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
• Positive HIV, HBV or HCV tests
• Participation in any other clinical study within 30 days prior to the onset of the study
• Enrolment in any other clinical study during the study period

Sponsors & Collaborators

• Sanaria Inc.: lead
• Radboud University Medical Center: collaborator

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, 6500 HB, Netherlands

Location

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Robert Sauerwein, MD

  Radboud University Medical Center

  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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2012
• First Posted: November 20, 2012
• Study Start: September 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: February 1, 2014
• Last Updated: May 15, 2017

Record last verified: 2014-05

Locations

NL (1)