Trial Outcomes & Findings for A Community Setting Study of Malaria After Systematic Treatment of Symptomatic Carriers of P. Falciparum With COA566 (Coartem®) (NCT NCT01256658)

Last Updated: 2014-02-10

Results Overview

Data is presented "per cluster". Number of Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000s) per person-year in infants and children (\<5 years) in post Community Screening Campaign (CSC) at month 12 was detected by Rapid Diagnostic Test (RDT) (using a blood sample from each participant) and later confirmed to have a parasite density ≥5000/uL by microscopy. Number of SMRC5000: sum of all SMRC5000 for all infants and children (\<5 years) in post CSC. Person-year observed: sum of duration (in days) for all infants and children (\<5 years) in post CSC present in study /365.25. Number of SMRC5000 per person-year = number of SMRC5000/person-year observed.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

14075 participants

Primary outcome timeframe

Month 12 of period 1

Results posted on

2014-02-10

Participant Flow

This was an 18 clusters randomized study (1 cluster = 1 village). 14,075 participants were recruited during Period 1 (treatment); of these, 12,226 participants continued onto Period 2 (1 year follow-up) to assess longer term impact of initial intervention on malaria episodes. Period 2 was stopped and all participants discontinued.

During period 1 clusters were randomized 1:1 to either the control or the intervention arm (9 clusters per arm). In the intervention arm subjects were screened for asymptomatic carriage of P. falciparum status and treated with COA566. In both arms, subjects were treated for symptomatic malaria episodes. During period 2 there was no study treatment.

Participant milestones

Participant milestones
Measure	Intervention Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control Participants received COA566 treatment for symptomatic malaria episodes only.
Period 1 STARTED	6817	7258
Period 1 COMPLETED	5897	6510
Period 1 NOT COMPLETED	920	748
Period 2 - Follow up Only - No Treatment STARTED	5854	6372
Period 2 - Follow up Only - No Treatment Lost to Follow up	71	77
Period 2 - Follow up Only - No Treatment Death	6	8
Period 2 - Follow up Only - No Treatment Study Termination	5777	6287
Period 2 - Follow up Only - No Treatment COMPLETED	0	0
Period 2 - Follow up Only - No Treatment NOT COMPLETED	5854	6372

Reasons for withdrawal

Reasons for withdrawal
Measure	Intervention Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control Participants received COA566 treatment for symptomatic malaria episodes only.
Period 1 Lost to Follow-up	837	661
Period 1 Withdrawal by Subject	35	43
Period 1 Death	48	44

Baseline Characteristics

A Community Setting Study of Malaria After Systematic Treatment of Symptomatic Carriers of P. Falciparum With COA566 (Coartem®)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intervention n=6817 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=7258 Participants Participants received COA566 treatment for symptomatic malaria episodes only.	Total n=14075 Participants Total of all reporting groups
Age, Continuous	23.02 years STANDARD_DEVIATION 20.67 • n=93 Participants	22.62 years STANDARD_DEVIATION 20.31 • n=4 Participants	22.82 years STANDARD_DEVIATION 20.63 • n=27 Participants
Sex: Female, Male Female	3656 Participants n=93 Participants	3816 Participants n=4 Participants	7472 Participants n=27 Participants
Sex: Female, Male Male	3161 Participants n=93 Participants	3442 Participants n=4 Participants	6603 Participants n=27 Participants

PRIMARY outcome

Timeframe: Month 12 of period 1

Population: The number of units represents the number of clusters that include all randomized infants and children (\<5 years) for which CSCs 1, 2, and 3 were conducted, data was available, and census data were obtained as per protocol.

Outcome measures

Outcome measures
Measure	Intervention n=9 number of units Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=9 number of units Participants received COA566 treatment for symptomatic malaria episodes only.
Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000s) Per Person-year in Infants and Children (<5 Years) in Post Community Screening Campaign (CSC) at Month 12 (Per Cluster)	1.69 SMRC5000 per person-year Standard Deviation 0.436	1.60 SMRC5000 per person-year Standard Deviation 0.526

PRIMARY outcome

Timeframe: Day 1 and day 28 of period 1

Population: The number of units represents the number of clusters that include all randomized, \> 6 months of age participants for which CSC1 was conducted, data was available and census data were obtained as per protocol.

Data is presented "per cluster". Change in hemoglobin levels from day 1 to day 28 was measured using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each asymptomatic carrier from Community Screening Campaign 1 (CSC1), \> 6 months of age, at day 1 and at day 28.

Outcome measures

Outcome measures
Measure	Intervention n=9 number of units Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=9 number of units Participants received COA566 treatment for symptomatic malaria episodes only.
Change in Hemoglobin Level (g/dL) in Asymptomatic Carriers >6 Months of Age (Per Cluster) Day 1 (n = 2387, 2116)	11.81 g/dL Standard Deviation 0.329	12.06 g/dL Standard Deviation 0.345
Change in Hemoglobin Level (g/dL) in Asymptomatic Carriers >6 Months of Age (Per Cluster) Day 28 (n = 1136, 1091)	12.33 g/dL Standard Deviation 0.318	11.86 g/dL Standard Deviation 0.373

SECONDARY outcome

Timeframe: Month 12 - period 1

Population: The number of units represents the number of clusters that include all randomized participants for which CSC4 was conducted, data was available, and census data were obtained as per protocol.

Data is presented "per cluster". Microscopy confirmed gametocyte carriers at Community Screening Campaign 4(CSC4) were assessed via microscopy at month 12 of period 1. Blood films were histologically treated and examined microscopically.

Outcome measures

Outcome measures
Measure	Intervention n=9 number of units Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=9 number of units Participants received COA566 treatment for symptomatic malaria episodes only.
Microscopy-confirmed Gametocyte Carriers at Community Screening Campaign 4 (CSC4) (Per Cluster)	4.9 participants Standard Error 0.41	5.1 participants Standard Error 0.41

SECONDARY outcome

Timeframe: Month 12 - period 1

Population: The number of units represents the number of clusters that include all randomized participants for which CSC4 was conducted, data was available, and census data was obtained as per protocol.

Data is presented "per cluster". Microscopy confirmation of asymptomatic carriers of P. falciparum at Community Screening Campaign 4 (CSC4) was conducted at month 12. Blood films were histologically treated and examined microscopically. When it was ascertained that P. falciparum was present, a count of the asexual forms against leukocytes was made using a tally counter.

Outcome measures

Outcome measures
Measure	Intervention n=9 number of units Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=9 number of units Participants received COA566 treatment for symptomatic malaria episodes only.
Microscopy Confirmed Asymptomatic Carriers of P. Falciparum at Community Screening Campaign 4 (CSC4) (Per Cluster)	34.6 participants Standard Error 1.86	37.6 participants Standard Error 1.86

SECONDARY outcome

Timeframe: Day 1 (CSC1/day 1) and month 12 (CSC4/day 1) - period 1

Population: The number of units represents the number of clusters that include all infants and children (\>6 months and \<5 years) randomized participants for which CSCs 1 and 4 were conducted, data was available, and census data were obtained as per protocol.

Data is presented "per cluster". Comparison of hemoglobin level (g/dL) from Community Screening Campaign 1 (CSC1)/Day 1 to Community Screening Campaign 4 (CSC4)/Day 1 in infants and children (\>6 months and \<5 years) by study arm was measured using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant.

Outcome measures

Outcome measures
Measure	Intervention n=9 number of units Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=9 number of units Participants received COA566 treatment for symptomatic malaria episodes only.
Change in Hemoglobin Level (g/dL) From Community Screening Campaign 1(CSC1)/Day 1 to Community Screening Campaign 4 (CSC4)/Day 1 (Per Cluster) CSC1/Day 1 (n= 819, 827)	10.24 g/dL Standard Deviation 0.371	10.04 g/dL Standard Deviation 0.476
Change in Hemoglobin Level (g/dL) From Community Screening Campaign 1(CSC1)/Day 1 to Community Screening Campaign 4 (CSC4)/Day 1 (Per Cluster) CSC4/Day 1 (n= 348,321)	10.99 g/dL Standard Deviation 0.267	11.13 g/dL Standard Deviation 0.360

SECONDARY outcome

Timeframe: 12 months - period 1

Population: Individual subject data from eligible clusters set defined as all randomized participants for which CSCs 1, 2, 3 and 4 were conducted, data was available, and census data were obtained as per protocol.

Number of Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000s) per person-year in post Community Screening Campaign (CSC), by study arm (individual level data) was detected by Rapid Diagnostic Test (RDT) (using a blood sample from each participant) and later confirmed to have a parasite density ≥5000/uL by microscopy. Number of SMRC5000: sum of all SMRC5000 for all subjects in post CSC. Person-year observed: sum of duration (in days) in post CSC for all subjects present in study /365.25. Number of SMRC5000 per person-year = number of SMRC5000/person-year observed.

Outcome measures

Outcome measures
Measure	Intervention n=6817 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=7258 Participants Participants received COA566 treatment for symptomatic malaria episodes only.
Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000s) Per Person-year in Post Community Screening Campaign (CSC)	0.45 SMRC5000 per person-year	0.39 SMRC5000 per person-year

SECONDARY outcome

Timeframe: 12 months - period 1

Population: Safety analyzable asymptomatic carriers set consisted of all consenting inhabitants from intervention clusters confirmed positive by RDT for P. falciparum asexual forms at any CSC or when migrating into the cluster, in the absence of clinical signs and symptoms who received at least one dose of COA566 to treat the diagnosed asymptomatic infection.

Total number of participants (all ages) with hospitalizations, severe malaria episodes or death after Community Screening Campaign (CSC) was assessed.

Outcome measures

Outcome measures
Measure	Intervention n=6817 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=7258 Participants Participants received COA566 treatment for symptomatic malaria episodes only.
Number of Participants With Hospitalizations, Severe Malaria Episodes or Death Post Community Screening Campaign (CSC) Hospitalizations	68 participants	57 participants
Number of Participants With Hospitalizations, Severe Malaria Episodes or Death Post Community Screening Campaign (CSC) Severe malaria episodes	10 participants	9 participants
Number of Participants With Hospitalizations, Severe Malaria Episodes or Death Post Community Screening Campaign (CSC) Death	31 participants	31 participants

SECONDARY outcome

Timeframe: 12 months - period 1

Population: Safety analyzable carriers set consisted of all infants and children (\> 6 months and \< 5 years)) from intervention clusters confirmed positive for P. falciparum asexual forms at any CSC or when migrating into the cluster, who in the absence of clinical signs and symptoms received at least one dose of COA566 for the diagnosed asymptomatic infection.

Total number of participants (infants and children (\> 6 months and \< 5 years)) with hospitalizations, severe malaria episodes or death after Community Screening Campaign (CSC) was assessed.

Outcome measures

Outcome measures
Measure	Intervention n=1023 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=1040 Participants Participants received COA566 treatment for symptomatic malaria episodes only.
Number of Participants (Infants and Children (> 6 Months and < 5 Years)) With Hospitalizations, Severe Malaria Episodes or Death Post Community Screening Campaign (CSC) Severe malaria episodes	4 participants	5 participants
Number of Participants (Infants and Children (> 6 Months and < 5 Years)) With Hospitalizations, Severe Malaria Episodes or Death Post Community Screening Campaign (CSC) Hospitalizations	20 participants	21 participants
Number of Participants (Infants and Children (> 6 Months and < 5 Years)) With Hospitalizations, Severe Malaria Episodes or Death Post Community Screening Campaign (CSC) Death	2 participants	2 participants

SECONDARY outcome

Timeframe: 12 months - period 1

Population: The number of units represents the number of clusters that include all randomized participants for which CSC 1, 2 3 and 4 was conducted, data was available, and census data were obtained as per protocol.

Data is presented "per cluster". Mean number of asymptomatic carriers from Community Screening Campaigns 1, 2, 3 and 4 (CSC1, CSC2, CSC3 and CSC4) was measured by confirmed positive microscopy for P. falciparum asexual forms in participants with absence of clinical signs and symptoms of malaria. Mean measured in this analysis is the mean percent indicting the mean of percentages of cluster frequencies under the study arm for that particular category.

Outcome measures

Outcome measures
Measure	Intervention n=9 number of units Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=9 number of units Participants received COA566 treatment for symptomatic malaria episodes only.
Mean of Microscopy-confirmed Asymptomatic Carriers From Community Screening Campaigns 1, 2, 3 and 4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster) CSC1/ day 1 (n= 2428, 1153)	42.8 participants Standard Deviation 5.67	47.5 participants Standard Deviation 8.05
Mean of Microscopy-confirmed Asymptomatic Carriers From Community Screening Campaigns 1, 2, 3 and 4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster) CSC2/ day 1 (n= 237, 833)	4.1 participants Standard Deviation 1.62	35.7 participants Standard Deviation 4.94
Mean of Microscopy-confirmed Asymptomatic Carriers From Community Screening Campaigns 1, 2, 3 and 4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster) CSC3/ day 1 (n= 171, 741)	2.8 participants Standard Deviation 0.92	32.2 participants Standard Deviation 9.26
Mean of Microscopy-confirmed Asymptomatic Carriers From Community Screening Campaigns 1, 2, 3 and 4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster) CSC4/ day 1 (n= 2023, 815)	34.4 participants Standard Deviation 3.92	37.8 participants Standard Deviation 6.37

SECONDARY outcome

Timeframe: 12 months - period 1

Population: Eligible clusters set consisted of all randomized participants for which CSCs 1, 2, 3 and 4 were conducted, data was available, and census data were obtained as per protocol.

Data is presented "per cluster". Mean number of gametocyte carriers at Day 1 for Community Screening Campaign 1,2,3,4 (CSC1, CSC2, CSC3 and CSC4) was measured using gametocyte assessments (prevalence and density) via microscopy. Mean measured in this analysis is the mean percent indicating the mean of percentages of cluster frequencies under the study arm for that particular category.

Outcome measures

Outcome measures
Measure	Intervention n=9 number of units Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=9 number of units Participants received COA566 treatment for symptomatic malaria episodes only.
Mean Number of Microscopy-confirmed Gametocyte Carriers at Day 1 of Community Screening Campaign 1,2,3,4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster) CSC1/Day 1 (n= 543, 246)	9.5 participants Standard Deviation 2.95	10.2 participants Standard Deviation 4.54
Mean Number of Microscopy-confirmed Gametocyte Carriers at Day 1 of Community Screening Campaign 1,2,3,4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster) CSC2/Day 1 (n= 33, 130)	0.6 participants Standard Deviation 0.38	5.5 participants Standard Deviation 2.54
Mean Number of Microscopy-confirmed Gametocyte Carriers at Day 1 of Community Screening Campaign 1,2,3,4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster) CSC3/Day 1 (n= 23, 144)	0.4 participants Standard Deviation 0.40	5.8 participants Standard Deviation 1.77
Mean Number of Microscopy-confirmed Gametocyte Carriers at Day 1 of Community Screening Campaign 1,2,3,4 (CSC1, CSC2, CSC3 and CSC4) (Per Cluster) CSC4/Day 1 (n= 279, 113)	4.8 participants Standard Deviation 1.34	5.1 participants Standard Deviation 1.38

SECONDARY outcome

Timeframe: Month 12 (CSC4/day 1) - period 1

Population: Individual subject data from eligible clusters set defined as all randomized participants for which CSC4 was conducted, data was available, and census data was obtained as per protocol.

Number of gametocyte carriers at Community Screening Campaign 4 (CSC4) was measured via microscopy and confirmed using Quantitative Reverse Transcription PCR (qRT-PCR) at day 1 of CSC4.

Outcome measures

Outcome measures
Measure	Intervention n=1023 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=976 Participants Participants received COA566 treatment for symptomatic malaria episodes only.
Number of Microscopy and qRT-PCR-confirmed Gametocyte Carriers at Community Screening Campaign 4 (CSC4) Positive	508 participants	462 participants
Number of Microscopy and qRT-PCR-confirmed Gametocyte Carriers at Community Screening Campaign 4 (CSC4) Negative	514 participants	511 participants
Number of Microscopy and qRT-PCR-confirmed Gametocyte Carriers at Community Screening Campaign 4 (CSC4) Not evaluable	1 participants	3 participants

SECONDARY outcome

Timeframe: Day 1 and day 28 - period 1

Population: Individual subject data from eligible clusters set defined as all infants and children (\>6 months and \<5 years) randomized for which CSC1 was conducted, data was available, and census data were obtained as per protocol.

Change in hemoglobin level (g/dL) from Community Screening Campaign 1 (CSC1)/Day 1 to CSC1/Day 28 in infants and children (\>6 Months and \<5 Years) for asymptomatic carriers at CSC1 was measured via hemoglobin levels using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. The anemic status is defined as follows: hemoglobin (Hb) \<5 g/dL = severe anemia, Hb 5 to \<8 g/dL = moderate anemia, Hb 8 to \<11 g/dL = mild anemia, Hb ≥11 g/dL = no anemia).

Outcome measures

Outcome measures
Measure	Intervention n=432 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=179 Participants Participants received COA566 treatment for symptomatic malaria episodes only.
Change in Hemoglobin Level (g/dL) From Community Screening Campaign 1 (CSC1)/Day 1 to CSC1/Day 28 in Infants and Children (>6 Months and <5 Years) for Asymptomatic Carriers at CSC1 CSC1/Day 1 (n=432 ; 179 )	9.78 g/dL Standard Deviation 1.763	9.67 g/dL Standard Deviation 1.707
Change in Hemoglobin Level (g/dL) From Community Screening Campaign 1 (CSC1)/Day 1 to CSC1/Day 28 in Infants and Children (>6 Months and <5 Years) for Asymptomatic Carriers at CSC1 CSC1/Day 28 (n=406 ; 174 )	10.95 g/dL Standard Deviation 1.543	10.17 g/dL Standard Deviation 1.748

SECONDARY outcome

Timeframe: Day 1 (CSC1/day 1) - period 1

Anemia status based on Community Screening Campaign 1 (CSC1)/Day 1 in infants and children (\>6 months and \<5 years) was measured via hemoglobin levels using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. The anemic status is defined as follows: hemoglobin (Hb) \<5 g/dL = severe anemia, Hb 5 to \<8 g/dL = moderate anemia, Hb 8 to \<11 g/dL = mild anemia, Hb ≥11 g/dL = no anemia).

Outcome measures

Outcome measures
Measure	Intervention n=819 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=348 Participants Participants received COA566 treatment for symptomatic malaria episodes only.
Anemia Status Based on Community Screening Campaign 1 (CSC1)/Day 1 in Infants and Children (>6 Months and <5 Years) CSC1/Day 1 Severe	3 participants	1 participants
Anemia Status Based on Community Screening Campaign 1 (CSC1)/Day 1 in Infants and Children (>6 Months and <5 Years) CSC1/Day 1 Moderate	80 participants	36 participants
Anemia Status Based on Community Screening Campaign 1 (CSC1)/Day 1 in Infants and Children (>6 Months and <5 Years) CSC1/Day 1 Mild	458 participants	195 participants
Anemia Status Based on Community Screening Campaign 1 (CSC1)/Day 1 in Infants and Children (>6 Months and <5 Years) CSC1/Day 1 No symptoms	278 participants	116 participants

SECONDARY outcome

Timeframe: Month 12 (CSC4/day 1) - period 1

Population: Individual subject data from eligible clusters set defined as all infants and children (\>6 months and \<5 years) randomized for which CSC4 was conducted, data was available, and census data was obtained as per protocol.

Anemia status based on Community Screening Campaign 4 (CSC4/Day 1) in infants and children (\>6 months and \<5 years) was measured via hemoglobin levels using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant. The anemic status is defined as follows: hemoglobin (Hb) \<5 g/dL = severe anemia, Hb 5 to \<8 g/dL = moderate anemia, Hb 8 to \<11 g/dL = mild anemia, Hb ≥11 g/dL = no anemia).

Outcome measures

Outcome measures
Measure	Intervention n=827 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=321 Participants Participants received COA566 treatment for symptomatic malaria episodes only.
Anemia Status Based on Community Screening Campaign 4 (CSC4)/Day 1 in Infants and Children (>6 Months and <5 Years) CSC4/Day 1 Severe	1 participants	1 participants
Anemia Status Based on Community Screening Campaign 4 (CSC4)/Day 1 in Infants and Children (>6 Months and <5 Years) CSC4/Day 1 Moderate	29 participants	9 participants
Anemia Status Based on Community Screening Campaign 4 (CSC4)/Day 1 in Infants and Children (>6 Months and <5 Years) CSC4/Day 1 Mild	349 participants	117 participants
Anemia Status Based on Community Screening Campaign 4 (CSC4)/Day 1 in Infants and Children (>6 Months and <5 Years) CSC4/Day 1 No	448 participants	194 participants

SECONDARY outcome

Timeframe: Day 1 (CSC1/day 1) and month 12 (CSC4/day 1) - period 1

Population: The number of units represents the number of clusters that include all randomized participants (ages 5-9 years, 10-14 years, and ≥15 years) clusters for which CSC1 and CSC4 was conducted, data was available, and census data were obtained as per protocol.

Data is presented "per cluster". Hemoglobin levels at Community Screening Campaign 1 and 4 (CSC1 and CSC4) on day 1 per age group (5-9 years, 10-14 years, and ≥15 years) in the intervention versus the control arm was measured using the HemoCue® rapid test. This test was performed using a drop of blood collected from the fingertip of each participant.

Outcome measures

Outcome measures
Measure	Intervention n=9 number of units Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=9 number of units Participants received COA566 treatment for symptomatic malaria episodes only.
Hemoglobin Level (g/dL) in Community Screening Campaign 1 (CSC1)/Day 1 and CSC4/Day 1 by Study Arm and Age Group (Per Cluster) CSC1 5- 9 years (n= 899, 431)	11.63 g/dL Standard Deviation 0.223	11.59 g/dL Standard Deviation 0.239
Hemoglobin Level (g/dL) in Community Screening Campaign 1 (CSC1)/Day 1 and CSC4/Day 1 by Study Arm and Age Group (Per Cluster) CSC4 5 - 9 years (n= 900, 396)	11.97 g/dL Standard Deviation 0.224	12.13 g/dL Standard Deviation 0.324
Hemoglobin Level (g/dL) in Community Screening Campaign 1 (CSC1)/Day 1 and CSC4/Day 1 by Study Arm and Age Group (Per Cluster) CSC1 10 - 14 years (n= 873, 380)	12.32 g/dL Standard Deviation 0.227	12.71 g/dL Standard Deviation 0.301
Hemoglobin Level (g/dL) in Community Screening Campaign 1 (CSC1)/Day 1 and CSC4/Day 1 by Study Arm and Age Group (Per Cluster) CSC4 10 - 14 years (n= 837, 359)	12.58 g/dL Standard Deviation 0.161	12.72 g/dL Standard Deviation 0.487
Hemoglobin Level (g/dL) in Community Screening Campaign 1 (CSC1)/Day 1 and CSC4/Day 1 by Study Arm and Age Group (Per Cluster) CSC1 >= 15 years (n= 2904, 1279)	13.13 g/dL Standard Deviation 0.304	13.49 g/dL Standard Deviation 0.355
Hemoglobin Level (g/dL) in Community Screening Campaign 1 (CSC1)/Day 1 and CSC4/Day 1 by Study Arm and Age Group (Per Cluster) CSC4 >= 15 years (n= 2760, 1136)	13.25 g/dL Standard Deviation 0.167	13.42 g/dL Standard Deviation 0.266

SECONDARY outcome

Timeframe: Day 7 of CSC1, CSC2 and CSC3 - period 1

Population: Treated asymptomatic carriers from CSC1, CSC2 and CSC3 confirmed by microscopy and treated with study medication. Subjects are counted multiple times if diagnosed and treated more than once during the study. Subjects missing day 7 parasitemia data are excluded. Percentages are based on the number of subjects treated with any formulation.

Percentage of participants with parasitological cure confirmed via microscopy at day 7 after treatment with COA566. This assessment was done on asymptomatic carriers from Community Screening Campaigns 1, 2 and 3 (CSC1, CSC2 and CSC3) from the intervention group only.

Outcome measures

Outcome measures
Measure	Intervention n=2450 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control Participants received COA566 treatment for symptomatic malaria episodes only.
Percentage of COA566-treated Microscopy-confirmed Asymptomatic Carriers at Community Screening Campaign 1, 2 and 3 (CSC1, CSC2 and CSC3) With Parasitological Cure Rate at Day 7 CSC1 (n= 2151)	99.5 percentage of participants	—
Percentage of COA566-treated Microscopy-confirmed Asymptomatic Carriers at Community Screening Campaign 1, 2 and 3 (CSC1, CSC2 and CSC3) With Parasitological Cure Rate at Day 7 CSC2 (n=182)	100 percentage of participants	—
Percentage of COA566-treated Microscopy-confirmed Asymptomatic Carriers at Community Screening Campaign 1, 2 and 3 (CSC1, CSC2 and CSC3) With Parasitological Cure Rate at Day 7 CSC3 (n=117)	96.7 percentage of participants	—

SECONDARY outcome

Timeframe: Day 1, day 7 and day 28 - period 1

Percentage of microscopy-confirmed gametocyte asymptomatic carriers treated with COA566 for asymptomatic carriers in Community Screening Campaign 1, 2 and 3 (CSC1, CSC2 and CSC3).

Outcome measures

Outcome measures
Measure	Intervention n=3970 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control Participants received COA566 treatment for symptomatic malaria episodes only.
Percentage of Microscopy-confirmed Gametocyte Carriers Treated With COA566 for Asymptomatic Carriers CSC3 Day 7 (n= 75)	0 percentage of participants	—
Percentage of Microscopy-confirmed Gametocyte Carriers Treated With COA566 for Asymptomatic Carriers CSC1 Day 1 (n= 3045)	15.7 percentage of participants	—
Percentage of Microscopy-confirmed Gametocyte Carriers Treated With COA566 for Asymptomatic Carriers CSC 1 Day 7 (n= 3045)	1.4 percentage of participants	—
Percentage of Microscopy-confirmed Gametocyte Carriers Treated With COA566 for Asymptomatic Carriers CSC 1 Day 28 (n= 3045)	0.1 percentage of participants	—
Percentage of Microscopy-confirmed Gametocyte Carriers Treated With COA566 for Asymptomatic Carriers CSC2 Day 1 (n= 850)	2.6 percentage of participants	—
Percentage of Microscopy-confirmed Gametocyte Carriers Treated With COA566 for Asymptomatic Carriers CSC2 Day 7 (n= 850)	0.1 percentage of participants	—
Percentage of Microscopy-confirmed Gametocyte Carriers Treated With COA566 for Asymptomatic Carriers CSC3 Day 1 (n= 75)	4.0 percentage of participants	—

SECONDARY outcome

Timeframe: Day 1 to Day 28- period 1

Individual data of number of asymptomatic carriers with increase in hemoglobin levels by at least 0.5 g/dL from Day 1 to Day 28 from Community Screening Campaign 1 (CSC1) infants and children (\>6 months and \<5 years). Hemoglobin levels were measured using the HemoCue® rapid test. This test was performed with a drop of blood collected from the fingertip at Day 1 and at Day 28.

Outcome measures

Outcome measures
Measure	Intervention n=434 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=180 Participants Participants received COA566 treatment for symptomatic malaria episodes only.
Number of Asymptomatic Carriers With Increase in Hemoglobin Levels by at Least 0.5 g/dL From Community Screening Campaign 1 (CSC1) Infants and Children (>6 Months and <5 Years)- Individual Data	288 participants	79 participants

SECONDARY outcome

Timeframe: Day 1 to day 28 - period 1

Population: The number of units represents the number of clusters that include all infants and children (\>6 months and \<5 years) randomized for which CSC1 was conducted, data was available, and census data were obtained as per protocol.

Data is presented "per cluster". Cluster data of number of asymptomatic carriers with increase in hemoglobin levels by at least 0.5 g/dL from Day 1 to Day 28 of Community Screening Campaign 1 (CSC1) in infants and children (\>6 months and \<5 years) was measured by Hemoglobin levels based on microscopy reading. Mean and Standard Deviation (SD) percent were measured indicating the mean and SD of percentages of cluster frequencies under the study arm for that particular category.

Outcome measures

Outcome measures
Measure	Intervention n=9 number of units Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=9 number of units Participants received COA566 treatment for symptomatic malaria episodes only.
Number of Asymptomatic Carriers With Increase in Hemoglobin Levels by at Least 0.5 g/dL From Day 1 to Day 28 of Community Screening Campaign 1 (CSC1) in Infants and Children (>6 Months and <5 Years)- Cluster Data	66.1 participants Standard Deviation 9.17	43.2 participants Standard Deviation 12.45

SECONDARY outcome

Timeframe: 12 months - period 1

Population: The number of units represents the number of clusters that include all participants randomized for which data on Symptomatic malaria episode, RDT-confirmed (SMRCs) were collected and census data were obtained as per protocol.

Data is presented "per cluster". Number of Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000) in asymptomatic carriers by study arm from all inhabitants diagnosed at any time for asymptomatic carriers. Number of SMRC5000s is measured by Rapid diagnostic test (RDT) and later confirmed to have a parasite density ≥ 5000/uL by microscopy.

Outcome measures

Outcome measures
Measure	Intervention n=9 number of units Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=9 number of units Participants received COA566 treatment for symptomatic malaria episodes only.
Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000) in Asymptomatic Carriers at Any Time of Diagnosis (Per Cluster) >3 SMRC5000	0.67 percentage of participants Standard Deviation 0.664	0.31 percentage of participants Standard Deviation 0.417
Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000) in Asymptomatic Carriers at Any Time of Diagnosis (Per Cluster) 1 SMRC5000	15.25 percentage of participants Standard Deviation 3.531	9.49 percentage of participants Standard Deviation 3.123
Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000) in Asymptomatic Carriers at Any Time of Diagnosis (Per Cluster) 2 SMRC5000	3.56 percentage of participants Standard Deviation 1.258	2.78 percentage of participants Standard Deviation 1.759
Number of Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL (SMRC5000) in Asymptomatic Carriers at Any Time of Diagnosis (Per Cluster) 3 SMRC5000	1.28 percentage of participants Standard Deviation 0.693	0.97 percentage of participants Standard Deviation 0.934

SECONDARY outcome

Timeframe: 12 months - period 1

Population: Individual subject data from eligible clusters set defined as all participants randomized for which data on Symptomatic malaria episode, RDT-confirmed (SMRCs) was collected and census data was obtained as per protocol.

Number of asymptomatic carriers diagnosed with 1 Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000), 2 SMRC5000, 3 SMRC5000 and \>3 SMRC5000 (complicated and uncomplicated episodes combined). Number of SMRC5000s is measured by Rapid diagnostic test (RDT) and later confirmed to have a parasite density ≥ 5000/uL by microscopy.

Outcome measures

Outcome measures
Measure	Intervention n=2740 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=1381 Participants Participants received COA566 treatment for symptomatic malaria episodes only.
Number of Asymptomatic Carriers With Complicated and Uncomplicated Episodes Combined 1 SMRC5000	413 participants	136 participants
Number of Asymptomatic Carriers With Complicated and Uncomplicated Episodes Combined 2 SMRC5000	96 participants	38 participants
Number of Asymptomatic Carriers With Complicated and Uncomplicated Episodes Combined 3 SMRC5000	34 participants	12 participants
Number of Asymptomatic Carriers With Complicated and Uncomplicated Episodes Combined >3 SMRC5000	17 participants	5 participants

SECONDARY outcome

Timeframe: Week 1 to Week 50

Population: Individual subject data from eligible randomized participants from Community Screening Campaign 1 (CSC1) for which data on Symptomatic malaria episode, RDT-confirmed (SMRCs) was collected and available form analysis and census data was obtained as per protocol.

Cumulative number of asymptomatic carriers having Symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000) from Week 1 to Week 50, was measured from group of participants diagnosed as asymptomatic carriers at Community Screening Campaign (CSC1)/Day1. Number of participants affected before and after diagnosed with ≥1 symptomatic malaria episode, RDT-confirmed, with parasitemia ≥5000/μL (SMRC5000) (complicated and uncomplicated episodes combined). Number of SMRC5000s was detected by Rapid Diagnostic Test (RDT) using a blood sample from each participant and later confirmed to have a parasite density \> or = 5000/uL by microscopy. Week (1-2) indicates day1 to day14, week (3-4) indicates day 15 to day 28, week (5-6) indicates day 29 to day 42, etc. After first diagnosis of asymptomatic carriers at CSC1/Day1.

Outcome measures

Outcome measures
Measure	Intervention n=2397 Participants Participants received COA566 treatment for asymptomatic carriage of P. falciparum and for symptomatic malaria episodes.	Control n=1138 Participants Participants received COA566 treatment for symptomatic malaria episodes only.
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (15-16) n at risk= 2390, 1102	4 participants	18 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (17-18) n at risk= 2390, 1102	4 participants	18 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (33-34) n at risk= 1931, 979	421 participants	121 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (1-2) n at risk= 2397, 1138	1 participants	4 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (3-4) n at risk= 2396, 1133	3 participants	8 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (5-6) n at risk= 2391, 1129	4 participants	12 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (7-8) n at risk= 2390, 1124	4 participants	13 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (9-10) n at risk= 2390, 1123	4 participants	15 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (11-12) n at risk= 2390, 1121	4 participants	17 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (13-14) n at risk= 2390, 1103	4 participants	18 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (19-20) n at risk= 2390, 1102	7 participants	20 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (35-36) n at risk= 1894, 968	440 participants	130 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (21-22) n at risk= 2337, 1083	30 participants	24 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (23-24) n at risk= 2311, 1077	92 participants	38 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (25-26) n at risk= 2246, 1063	188 participants	59 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (27-28) n at risk= 2148, 1041	287 participants	79 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (29-30) n at risk= 2047, 1020	347 participants	98 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (31-32) n at risk= 1979, 996	391 participants	114 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (37-38) n at risk= 1868, 956	460 participants	144 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (39-40) n at risk= 1837, 935	477 participants	149 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (41-42) n at risk= 1816, 927	483 participants	154 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (43-44) n at risk= 1805, 920	486 participants	158 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (45-46) n at risk= 1785, 913	490 participants	159 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (47-48) n at risk= 1773, 910	492 participants	161 participants
Cumulative Number of Subjects With Symptomatic Malaria Episode, RDT-confirmed, With Parasitemia ≥5000/μL From Week 1 to Week 50 Week (49-50) n at risk= 1758, 904	493 participants	161 participants

Adverse Events

Intervention - Period 1

Serious events: 156 serious events

Other events: 0 other events

Deaths: 0 deaths

Control - Period 1

Serious events: 134 serious events

Other events: 0 other events

Deaths: 0 deaths

Intervention - Period 2 - Follow-up Only

Serious events: 23 serious events

Other events: 0 other events

Deaths: 0 deaths

Control - Period 2- Follow-up Only

Serious events: 39 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Study Director

Novartis

Phone: 41 61 324 1111

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER