Trial Outcomes & Findings for A Study to Characterise the Antimalarial and Transmission Blocking Activity of a Single Dose of DSM265 or OZ439 in Healthy Subjects With Induced Blood Stage Plasmodium Falciparum or Plasmodium Vivax Infection (NCT NCT02573857)
NCT ID: NCT02573857
Last Updated: 2020-06-05
Results Overview
Efficacy of a single 400 mg dose of DSM265 or a 200mg dose of OZ439. The primary efficacy variable is parasite reduction ratio (PRR) of asexual parasites based on qPCR analysis of blood level parasitemia pre-dose and following administration of study drug. The parasite reduction ratio (PRR) provides an estimate of the efficacy of an antimalarial treatment and is the ratio of the parasite density between admission and 48 h post antimalarial treatment.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
16 participants
Primary outcome timeframe
From baseline to 48 hours post antimalarial treatment
Results posted on
2020-06-05
Participant Flow
After reviewing the safety data obtained from the first 2 cohorts, the SRT decided not to enrol Cohort 3.
Participant milestones
| Measure |
DSM265 P. Falciparum
Cohort 1: the efficacy of a single administration of 400 mg DSM265 for the clearance of asexual blood stages of P. falciparum will be determined. Activity of a second single dose of 400 mg DSM265 against gametocytes will be assessed in this cohort only if sexual stages are identified by PCR following the initial drug treatment.
DSM265: Oral suspension from bulk powder
|
OZ439 P. Vivax
Cohort 2: subjects will be infected with P. vivax by IBSM, then treated with a single 200 mg dose OZ439. If recrudescence occurs following initial drug treatment with 200 mg OZ439, then affected participants who reach the treatment threshold will receive a single 400 mg dose of OZ439.
OZ439: Oral suspension from powder in a bottle
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Characterise the Antimalarial and Transmission Blocking Activity of a Single Dose of DSM265 or OZ439 in Healthy Subjects With Induced Blood Stage Plasmodium Falciparum or Plasmodium Vivax Infection
Baseline characteristics by cohort
| Measure |
DSM265 P. Falciparum
n=8 Participants
Cohort 1: the efficacy of a single administration of 400 mg DSM265 for the clearance of asexual blood stages of P. falciparum will be determined. Activity of a second single dose of 400 mg DSM265 against gametocytes will be assessed in this cohort only if sexual stages are identified by PCR following the initial drug treatment.
DSM265: Oral suspension from bulk powder
|
OZ439 P. Vivax
n=8 Participants
Cohort 2: subjects will be infected with P. vivax by IBSM, then treated with a single 200 mg dose OZ439. If recrudescence occurs following initial drug treatment with 200 mg OZ439, then affected participants who reach the treatment threshold will receive a single 400 mg dose of OZ439.
OZ439: Oral suspension from powder in a bottle
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
24.8 years
STANDARD_DEVIATION 4 • n=5 Participants
|
24.9 years
STANDARD_DEVIATION 4.6 • n=7 Participants
|
24.8 years
STANDARD_DEVIATION 4.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Body Mass Index
|
23.4 kg/m^2
STANDARD_DEVIATION 2 • n=5 Participants
|
22.6 kg/m^2
STANDARD_DEVIATION 2.8 • n=7 Participants
|
23 kg/m^2
STANDARD_DEVIATION 2.4 • n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline to 48 hours post antimalarial treatmentPopulation: Subject R104 in Cohort 1 was excluded from PRR analysis because parasitaemia was not observed in this subject.
Efficacy of a single 400 mg dose of DSM265 or a 200mg dose of OZ439. The primary efficacy variable is parasite reduction ratio (PRR) of asexual parasites based on qPCR analysis of blood level parasitemia pre-dose and following administration of study drug. The parasite reduction ratio (PRR) provides an estimate of the efficacy of an antimalarial treatment and is the ratio of the parasite density between admission and 48 h post antimalarial treatment.
Outcome measures
| Measure |
DSM265 P. Falciparum
n=7 Participants
Cohort 1: the efficacy of a single administration of 400 mg DSM265 for the clearance of asexual blood stages of P. falciparum will be determined. Activity of a second single dose of 400 mg DSM265 against gametocytes will be assessed in this cohort only if sexual stages are identified by PCR following the initial drug treatment.
DSM265: Oral suspension from bulk powder
|
OZ439 P. Vivax
n=8 Participants
Cohort 2: subjects will be infected with P. vivax by IBSM, then treated with a single 200 mg dose OZ439. If recrudescence occurs following initial drug treatment with 200 mg OZ439, then affected participants who reach the treatment threshold will receive a single 400 mg dose of OZ439.
OZ439: Oral suspension from powder in a bottle
|
|---|---|---|
|
Efficacy (PRR) of DSM265 or OZ439
|
603 PRR
Interval 410.0 to 886.0
|
46 PRR
Interval 36.0 to 61.0
|
PRIMARY outcome
Timeframe: From baseline to 48 hours post antimalarial treatmentPopulation: Redundant outcome measure. Results are reported in Outcome Measure 1 (Efficacy (PRR) of DSM265 or OZ439).
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: From challenge inoculum (day 0) up to day 28 (+/-3 days)Assessement of Adverse Events (AE) (unexpected toxicities, adverse events encountered during or after investigational drug administration)
Outcome measures
| Measure |
DSM265 P. Falciparum
n=8 Participants
Cohort 1: the efficacy of a single administration of 400 mg DSM265 for the clearance of asexual blood stages of P. falciparum will be determined. Activity of a second single dose of 400 mg DSM265 against gametocytes will be assessed in this cohort only if sexual stages are identified by PCR following the initial drug treatment.
DSM265: Oral suspension from bulk powder
|
OZ439 P. Vivax
n=8 Participants
Cohort 2: subjects will be infected with P. vivax by IBSM, then treated with a single 200 mg dose OZ439. If recrudescence occurs following initial drug treatment with 200 mg OZ439, then affected participants who reach the treatment threshold will receive a single 400 mg dose of OZ439.
OZ439: Oral suspension from powder in a bottle
|
|---|---|---|
|
Safety of DSM265 or OZ439 - Number of Adverse Events
|
53 Number of adverse events
|
107 Number of adverse events
|
SECONDARY outcome
Timeframe: From Drug administration up to day 28 (+/-3 days) following inoculumOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From challenge inoculum (day 0) and up to day 28 (+/-3 days)Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From From drug administration until Standard of Care administration, or up to day 28 (+/-3 days)Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From From drug administration until Standard of Care administration, or up to day 28 (+/-3 days)Outcome measures
Outcome data not reported
Adverse Events
DSM265 P. Falciparum
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
OZ439 P. Vivax
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
DSM265 P. Falciparum
n=8 participants at risk
Cohort 1: the efficacy of a single administration of 400 mg DSM265 for the clearance of asexual blood stages of P. falciparum will be determined. Activity of a second single dose of 400 mg DSM265 against gametocytes will be assessed in this cohort only if sexual stages are identified by PCR following the initial drug treatment.
DSM265: Oral suspension from bulk powder
|
OZ439 P. Vivax
n=8 participants at risk
Cohort 2: subjects will be infected with P. vivax by IBSM, then treated with a single 200 mg dose OZ439. If recrudescence occurs following initial drug treatment with 200 mg OZ439, then affected participants who reach the treatment threshold will receive a single 400 mg dose of OZ439.
OZ439: Oral suspension from powder in a bottle
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Muscle rigidity
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
12.5%
1/8 • Number of events 3 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Cardiac disorders
Tachycardia
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
25.0%
2/8 • Number of events 6 • Until end of study, 28 +/- 3 days
|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Gastrointestinal disorders
Abdominal tenderness
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
|
Gastrointestinal disorders
Gingival swelling
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 2 • Until end of study, 28 +/- 3 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
|
General disorders
Administration site haematoma
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
General disorders
Catheter site bruise
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
General disorders
Catheter site pain
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
General disorders
Chills
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
37.5%
3/8 • Number of events 4 • Until end of study, 28 +/- 3 days
|
|
General disorders
Fatigue
|
37.5%
3/8 • Number of events 3 • Until end of study, 28 +/- 3 days
|
37.5%
3/8 • Number of events 6 • Until end of study, 28 +/- 3 days
|
|
General disorders
Influenza like illness
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
|
General disorders
Malaise
|
37.5%
3/8 • Number of events 4 • Until end of study, 28 +/- 3 days
|
25.0%
2/8 • Number of events 2 • Until end of study, 28 +/- 3 days
|
|
General disorders
Peripheral swelling
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
|
General disorders
Pyrexia
|
25.0%
2/8 • Number of events 2 • Until end of study, 28 +/- 3 days
|
100.0%
8/8 • Number of events 24 • Until end of study, 28 +/- 3 days
|
|
General disorders
Vessel puncture site thrombosis
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
|
Infections and infestations
Upper respiratory tract infection
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 2 • Until end of study, 28 +/- 3 days
|
|
Injury, poisoning and procedural complications
Contusion
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
62.5%
5/8 • Number of events 10 • Until end of study, 28 +/- 3 days
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
62.5%
5/8 • Number of events 5 • Until end of study, 28 +/- 3 days
|
|
Investigations
Cardiac murmur
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
37.5%
3/8 • Number of events 4 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.0%
2/8 • Number of events 2 • Until end of study, 28 +/- 3 days
|
50.0%
4/8 • Number of events 5 • Until end of study, 28 +/- 3 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
25.0%
2/8 • Number of events 5 • Until end of study, 28 +/- 3 days
|
50.0%
4/8 • Number of events 10 • Until end of study, 28 +/- 3 days
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Nervous system disorders
Headache
|
50.0%
4/8 • Number of events 8 • Until end of study, 28 +/- 3 days
|
75.0%
6/8 • Number of events 19 • Until end of study, 28 +/- 3 days
|
|
Nervous system disorders
Lethargy
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Respiratory, thoracic and mediastinal disorders
Diaphragmalgia
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 2 • Until end of study, 28 +/- 3 days
|
|
Skin and subcutaneous tissue disorders
Erythema
|
37.5%
3/8 • Number of events 3 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Skin and subcutaneous tissue disorders
Rash generalised
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/8 • Until end of study, 28 +/- 3 days
|
12.5%
1/8 • Number of events 1 • Until end of study, 28 +/- 3 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60