Helminthes; Infestation, Intestinal
Conditions
Keywords
soil-transmitted helminths, pediatric, adult, albendazole, ivermectin, coformulation
Brief summary
The purpose of this clinical trial is to evaluate a fixed-dose co-formulation (FDC) of ivermectin and albendazole for the treatment of all Soil Transmitted helminths (STH). The current strategy to control STH in endemic areas is mass administration of albendazole or mebendazole, mainly to pre-school and school-aged children. Although this treatment works well for some STH species, efficacy against Trichuris trichiura is poor and it is not effective Strongyloides stercoralis. Thus new drugs or drug combinations are an urgent priority to increase the effectiveness of control programmes. Furthermore, the World Health Organisation has recommended combination therapy of ivermectin with albendazole. The trial proposed, is an adaptive phase II/III trial where the phase II component will evaluate the safety of the FDC as a single dose or 3-day single dose regimen for the treatment of T. trichiura in paediatric population. After analysis of the safety results the phase III trial will be executed to evaluate the efficacy of the FDC as a single dose or 3-day single dose regimen compared to the standard single dose regimen of ALB (400 mg) for the treatment of T. trichiura, hookworm and S. stercoralis in paediatric and young adult population. The estimated total sample size for the adaptive design (phase II and III component) is 1223 participants. Of these, 126 will be enrolled in the phase II and 1097 in the phase III components respectively in an adaptive trial design.
Detailed description
An adaptive phase II/III clinical trial to evaluate the Safety and Efficacy of a Single Day or 3-day Single Dose of an ALBENDAZOLE-IVERMECTIN Coformulation vs ALBENDAZOLE for the Treatment of Soil-Transmitted Helminth Infections. The estimated total sample size for the adaptive design (phase II and III components) is 1223 participants. Of these, 126 will be enrolled in the phase II and 1097 in the phase III components. Phase II component (Kenya only) Unicentric, 3-arm, parallel, open-label, individually randomised, phase II trial to determine in three weight groups, the safety of the ALBENDAZOLEIVERMECTIN Co-formulation given as a Single Day or 3-day Single Dose regimen for the treatment of Trichuris trichiura in children and young adult aged between 5 to 18 years. Estimated sample size: 126 participants Participants will be stratified in three different weight groups in order to gradually increase the dose of ivermectin in the Fixed Dose Co-formulation (FDC): * Group 1 (38 participants): with body weight of 23-\<30 Kg will receive 300-391 µg/Kg IVM (FDC 400mg-9mg) or ALB * Group 2 (38 participants): with body weight of 30-45 Kg will receive 400-600 µg/Kg IVM (FDC 400mg-18mg) or ALB. * Group 3 (50 participants): with body weight of 15-23 Kg will receive 391-600 µg/Kg IVM (FDC 400mg-9mg) or ALB. Where FDC stands for Fixed Dose Co-formulation and ALB stands for Albendazole. Then, the participants will be allocated to one of the three study arms with unequal probability (ALB: p=0.2, n=26; FDCx1: p=0.4, n=50; FDCx3: p=0.4, n=50) starting with group 1. * Treatment Arm 1: Single dose of a tablet of ALBENDAZOLE 400 mg (active control arm). * Treatment Arm 2: Single dose of a tablet of ALBENDAZOLEIVERMECTIN Co-formulation. * Treatment Arm 3: Daily dose of a tablet of ALBENDAZOLE-IVERMECTIN Co-formulation for 3 consecutive days. Phase III Component A multi-centre, 3-arm, parallel, open-label, randomised, phase III trial to compare safety and efficacy of the active control arm (current standard of care) against 2 experimental arms for the treatment of T. trichiura, hookworm and S. stercoralis, in children and young adult aged between 5-18 years in three subSaharan African countries (Ethiopia, Kenya and Mozambique) We hypothesise that the FDC of Ivermectin (IVM) and ALB either at single or 3- day regimens will be more effective against some species of Soil Transmitted Helminths (STH) (T. trichiura, hookworm and S. stercoralis) compared to the current use of a single dose regimen of 400mg ALB. Estimated sample size: 1097 participants Participants will be randomly allocated with unequal probability, according to the specific expected cure rate by treatment and specie, to one of the three study treatment arms. * Treatment Arm 1: Single dose of a tablet of ALB 400 mg (active control arm). * Treatment Arm 2: Single dose of a tablet of FDC 400mg-18mg or 400mg-9mg. * For participants \<45 kg of body weight at baseline: FDC of 400mg ALB- 9mg IVM. * For participants ≥45 kg of body weight at baseline: FDC of 400mg ALB-18mg IVM. * Treatment Arm 3: Daily dose of a tablet of FDC 400mg-18mg or 400mg9mg for 3 days. * For participants \<45 kg of body weight at baseline: FDC of 400mg ALB-9mg IVM. * For participants ≥45 kg of body weight at baseline: FDC of 400mg ALB- 18mg IVM. In the phase III component, allocation of participants to study arms will be done by block randomization and stratified by the species of STH. Treatment allocation for each study participant will be concealed in opaque sealed envelope that will be opened only after enrolment. Study participants will be assigned a unique number linked to the allocated treatment group. The phase II and III trial components comprise of a screening phase, an enrolment phase, a treatment phase, a post-treatment phase with follow-up visits, and early withdrawal/end-of-study evaluations. Participants recruited in Mozambique will be offered to be tested for HIV serostatus due to the high HIV prevalence in the country, but the result will not determine the participant's eligibility. In Kenya and Ethiopia, the low HIV prevalence does not justify HIV testing
Interventions
COMBINATION_PRODUCTAlbendazole and Ivermectin fixed dose coformulation
400 mg Albendazole - 9 mg Ivermectin OR 400 mg Albendazole - 18 mg Ivermectin
DRUGAlbendazole
Albendazole 400mg single dose
Sponsors
Leiden University Medical Center
Bahir Dar University
Centro de Investigacao em Saude de Manhica
London School of Hygiene and Tropical Medicine
Kenya Medical Research Institute
Laboratorios Liconsa
Universidad de León
European and Developing Countries Clinical Trials Partnership (EDCTP)
Barcelona Institute for Global Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Positive infection test by microscopy for at least one of the following STH: T. trichiura, hookworms and/or larvae of S. stercoralis. * Weight ≥15 Kg. * Male or female, aged 5 to 18 years. * Female participants who are ≥12 years old (or female post menarche) must have a negative urine pregnancy test at screening or at the time of randomization. * Ability to take oral medication and willingness to comply with all study procedures. * Parental acceptance to participate in the study by obtaining a signed and dated informed consent form approved by the Regulatory authorities. In addition, verbal assent will be obtained from children aged 12-18 years.
Exclusion criteria
* Intake of ALB, mebendazole and/or IVM, or any potentially interacting drug three months before screening. * Residence outside the study area or planning to move away in the four weeks following recruitment. * Epidemiological risk of infection by Loa loa. * Serious medical illness, per investigator's criteria. * Any participant's condition that would prevent the appropriate evaluation and followup, as per investigator's criteria. * Known hypersensitivity to any components of either of the study treatment. * Positive pregnancy urine test, pregnant or first week postpartum.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cure Rate for T. Trichiura (CR) | 21 days | For Trichuris trichiura, the cure rate is defined as the proportion of participants who test negative for T. trichiura eggs in the Kato-Katz fecal examination on day 21 post-treatment, relative to the total number of participants infected at baseline (n=636). |
| Frequency of Related Adverse Events | 21 days postreatment | Proportions of participants presenting at least one treatment-related adverse event by arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Egg Reduction Rate for Hookworm (ERR) | 21 days | The Egg Reduction Rate (ERR) is defined as the percentage reduction in the geometric mean (GM) of eggs per gram (EPG) of feces from baseline to post-treatment. |
| Cure Rates for for S. Stercoralis | 21 days | For S. stercoralis, the cure rate is defined as the proportion of participants who test negative for S. stercoralis larvae in the Baermann tesi on day 21 post-treatment, relative to the total number of participants infected at baseline in Phase III (n=97). |
| Egg Reduction Rate for T. Trichiura (ERR) | 21 days | The Egg Reduction Rate (ERR) is defined as the percentage reduction in the geometric mean (GM) of eggs per gram (EPG) of feces from baseline to post-treatment. |
| To Evaluate the Frequency of Known ALB Resistant Alleles in Hookworm and T. Trichiura in the Three Treatment Arms Before and After Treatment. | 21 days | The original objective as per the protocol was to To evaluate the frequency of known ALB resistant alleles in hookworm and T. trichiura in the three treatment arms before and after treatment with the endpoint being Evaluation of genotypic albendazole resistance in the three arms. This objective was based on the hypothesis that mutations at codons 167, 198, and 200 of the beta-tubulin gene of Trichuris trichiura were associated with resistance. However, since this time, it has become increasingly evident, based on research from us (PMID: 35895348, 39546832, 34563247) and others, that this hypothesis is no longer supported, and that the genetic determinants of resistance in T. trichiura are yet to be discovered. Therefore, we have begun evaluating, using whole genome sequencing, other genetic variants and their association with poor treatment response. This research is exploratory and ongoing. Therefore, the original outcome as defined in the protocol could not be assessed. |
| Cure Rate for T. Trichiura (CR) by qPCR | 21 days | For Trichuris trichiura, the cure rate is defined as the proportion of participants who test negative by qPCR (Ct-value\>35) on day 21 post-treatment, relative to the total number of participants that were positves at baseline by Kato-Katz and qPCR (n=534). |
| Cure Rate for for Hookworm (CR) | 21 days | For hookworm, the cure rate is defined as the proportion of participants who test negative for hookworm eggs in the Kato-Katz fecal examination on day 21 post-treatment, relative to the total number of participants infected at baseline in Phase III (n=350). |
Countries
Ethiopia, Kenya, Mozambique
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Albendazole Single dose of Albendazole 400mg | 243 |
| Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) Single dose 400mg Albendazole- 9mg Ivermectin for participants \<45 kg of body weight Single dose 400mg Albendazole- 18mg Ivermectin for participants \>= 45 kg of body weight | 381 |
| Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) Daily dose of 400mg Albendazole- 9mg Ivermectin for 3 consecutive days for participants \<45 kg of body weight Daily dose of 400mg Albendazole- 18mg Ivermectin for 3 consecutive days for participants \>= 45 kg of body weight | 377 |
| Total | 1,001 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Phase II | Eligibility criteria | 0 | 1 | 0 |
| Phase II | Withdrawal by Subject | 6 | 2 | 3 |
| Phase III | Lost to Follow-up | 1 | 0 | 0 |
| Phase III | Withdrawal by Subject | 6 | 4 | 4 |
Baseline characteristics
| Characteristic | Albendazole | Total | Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) | Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) |
|---|---|---|---|---|
| Age, Continuous Phase II | 9.0 Years STANDARD_DEVIATION 2.55 | 9.1 Years STANDARD_DEVIATION 2.65 | 9.2 Years STANDARD_DEVIATION 2.74 | 8.9 Years STANDARD_DEVIATION 2.66 |
| Age, Continuous Phase III | 11.4 Years STANDARD_DEVIATION 3.08 | 11.3 Years STANDARD_DEVIATION 3.13 | 11.3 Years STANDARD_DEVIATION 3.24 | 11.2 Years STANDARD_DEVIATION 3.05 |
| Eggs per gram (EPG) detected by Kato-Katz technique in participants infected with hookworm Phase II | 42.6 Eggs per gram of stool STANDARD_DEVIATION 0.2 | 159.2 Eggs per gram of stool STANDARD_DEVIATION 1.9 | 93.0 Eggs per gram of stool STANDARD_DEVIATION 2.3 | 527.3 Eggs per gram of stool STANDARD_DEVIATION 1.5 |
| Eggs per gram (EPG) detected by Kato-Katz technique in participants infected with hookworm Phase III | 116.6 Eggs per gram of stool STANDARD_DEVIATION 1.3 | 115.9 Eggs per gram of stool STANDARD_DEVIATION 1.3 | 112.9 Eggs per gram of stool STANDARD_DEVIATION 1.4 | 118.2 Eggs per gram of stool STANDARD_DEVIATION 1.3 |
| Eggs per gram (EPG) detected by Kato-Katz technique in participants infected with T. trchiura Phase II | 113.0 Eggs per gram of stool STANDARD_DEVIATION 1.2 | 139.6 Eggs per gram of stool STANDARD_DEVIATION 1.4 | 159.4 Eggs per gram of stool STANDARD_DEVIATION 1.4 | 137.4 Eggs per gram of stool STANDARD_DEVIATION 1.5 |
| Eggs per gram (EPG) detected by Kato-Katz technique in participants infected with T. trchiura Phase III | 128.0 Eggs per gram of stool STANDARD_DEVIATION 1.5 | 123.9 Eggs per gram of stool STANDARD_DEVIATION 1.5 | 121.6 Eggs per gram of stool STANDARD_DEVIATION 1.5 | 124.2 Eggs per gram of stool STANDARD_DEVIATION 1.4 |
| Number of subjects positive for infection with Hookworms Phase II | 2 Participants | 10 Participants | 4 Participants | 4 Participants |
| Number of subjects positive for infection with Hookworms Phase III | 106 Participants | 350 Participants | 120 Participants | 124 Participants |
| Number of subjects positive for infection with S. stercoralis Phase II | 0 Participants | 7 Participants | 3 Participants | 4 Participants |
| Number of subjects positive for infection with S. stercoralis Phase III | 16 Participants | 97 Participants | 41 Participants | 40 Participants |
| Number of subjects positive for infection with T. trichiura Phase II | 30 Participants | 135 Participants | 54 Participants | 51 Participants |
| Number of subjects positive for infection with T. trichiura Phase III | 101 Participants | 501 Participants | 200 Participants | 200 Participants |
| Race (NIH/OMB) Phase II American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase II Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase II Black or African American | 30 Participants | 135 Participants | 54 Participants | 51 Participants |
| Race (NIH/OMB) Phase II More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase II Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase II Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase II White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase III American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase III Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase III Black or African American | 213 Participants | 866 Participants | 323 Participants | 330 Participants |
| Race (NIH/OMB) Phase III More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase III Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase III Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Phase III White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Ethiopia Phase II | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Ethiopia Phase III | 96 Participants | 307 Participants | 104 Participants | 107 Participants |
| Region of Enrollment Kenya Phase II | 30 Participants | 135 Participants | 54 Participants | 51 Participants |
| Region of Enrollment Kenya Phase III | 84 Participants | 397 Participants | 155 Participants | 158 Participants |
| Region of Enrollment Mozambique Phase II | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Mozambique Phase III | 33 Participants | 162 Participants | 64 Participants | 65 Participants |
| Sex: Female, Male Phase II Female | 20 Participants | 79 Participants | 31 Participants | 28 Participants |
| Sex: Female, Male Phase II Male | 10 Participants | 56 Participants | 23 Participants | 23 Participants |
| Sex: Female, Male Phase III Female | 113 Participants | 457 Participants | 179 Participants | 165 Participants |
| Sex: Female, Male Phase III Male | 100 Participants | 409 Participants | 144 Participants | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 243 | 0 / 381 | 0 / 377 |
| other Total, other adverse events | 50 / 243 | 99 / 381 | 107 / 377 |
| serious Total, serious adverse events | 0 / 243 | 0 / 381 | 0 / 377 |
Outcome results
Primary
Cure Rate for T. Trichiura (CR)
For Trichuris trichiura, the cure rate is defined as the proportion of participants who test negative for T. trichiura eggs in the Kato-Katz fecal examination on day 21 post-treatment, relative to the total number of participants infected at baseline (n=636).
Time frame: 21 days
Population: Intention to treat population infected with Trichuris trichiura from both Phase II and Phase III of the study (n=636).~A separate efficacy analysis by phase was not conducted, as the protocol specifies that the required sample size for this outcome is derived from all participants infected with T. trichiura at baseline, combining those from Phase II and Phase III.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Albendazole | Cure Rate for T. Trichiura (CR) | 47 Participants |
| Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) | Cure Rate for T. Trichiura (CR) | 208 Participants |
| Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) | Cure Rate for T. Trichiura (CR) | 247 Participants |
Comparison: pairwise comparisons of cure rates within the three study groups, considering an overall significance level of 0.05. To account for multiple testing, a Bonferroni correction was applied, resulting in an adjusted significance level of 0.0167p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Pairwise comparisons of cure rates within the three study groups, considering an overall significance level of 0.05. To account for multiple testing, a Bonferroni correction was applied, resulting in an adjusted significance level of 0.0167p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Pairwise comparisons of cure rates within the three study groups, considering an overall significance level of 0.05. To account for multiple testing, a Bonferroni correction was applied, resulting in an adjusted significance level of 0.0167p-value: <0.0001Cochran-Mantel-Haenszel
Primary
Frequency of Related Adverse Events
Proportions of participants presenting at least one treatment-related adverse event by arm
Time frame: 21 days postreatment
Population: Intention-to-Treat (ITT) population from both Phase II and Phase III (n = 1001), regardless of baseline infection type (T. trichiura, hookworms, or S. stercoralis).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Albendazole | Frequency of Related Adverse Events | ITT Phase III | 31 Participants |
| Albendazole | Frequency of Related Adverse Events | ITT Phase II and Phase III | 34 Participants |
| Albendazole | Frequency of Related Adverse Events | ITT Phase II | 3 Participants |
| Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) | Frequency of Related Adverse Events | ITT Phase III | 67 Participants |
| Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) | Frequency of Related Adverse Events | ITT Phase II and Phase III | 75 Participants |
| Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) | Frequency of Related Adverse Events | ITT Phase II | 8 Participants |
| Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) | Frequency of Related Adverse Events | ITT Phase III | 78 Participants |
| Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) | Frequency of Related Adverse Events | ITT Phase II and Phase III | 88 Participants |
| Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) | Frequency of Related Adverse Events | ITT Phase II | 10 Participants |
Secondary
Cure Rate for for Hookworm (CR)
For hookworm, the cure rate is defined as the proportion of participants who test negative for hookworm eggs in the Kato-Katz fecal examination on day 21 post-treatment, relative to the total number of participants infected at baseline in Phase III (n=350).
Time frame: 21 days
Population: Intention to treat population infected with hookworm from Phase III of the study (n=350).~A separate efficacy analysis by phase was not conducted, as the protocol specifies that the required sample size for this outcome is derived exclusively from participants infected with hookworms at baseline in Phase III.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Albendazole | Cure Rate for for Hookworm (CR) | 69 Participants |
| Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) | Cure Rate for for Hookworm (CR) | 99 Participants |
| Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) | Cure Rate for for Hookworm (CR) | 114 Participants |
Comparison: Pairwise comparisons of cure rates were conducted between Albendazole and FDCx3, as well as FDCx1 and FDCx3, but not between Albendazole and FDCx1, since both contain the same dose regimen of the active drug. An overall significance level of 0.05 was considered, and to account for multiple testing, a Bonferroni correction was applied.p-value: <0.0001Mantel Haenszel
Comparison: Pairwise comparisons of cure rates were conducted between Albendazole and FDCx3, as well as FDCx1 and FDCx3, but not between Albendazole and FDCx1, since both contain the same dose regimen of the active drug. An overall significance level of 0.05 was considered, and to account for multiple testing, a Bonferroni correction was applied.p-value: =0.0007Cochran-Mantel-Haenszel
Secondary
Cure Rate for T. Trichiura (CR) by qPCR
For Trichuris trichiura, the cure rate is defined as the proportion of participants who test negative by qPCR (Ct-value\>35) on day 21 post-treatment, relative to the total number of participants that were positves at baseline by Kato-Katz and qPCR (n=534).
Time frame: 21 days
Population: For Trichuris trichiura, the cure rate is defined as the proportion of participants who test negative by qPCR (Ct-value\>35) on day 21 post-treatment, relative to the total number of participants that were positves at baseline by Kato-Katz and qPCR (n=534).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Albendazole | Cure Rate for T. Trichiura (CR) by qPCR | 55 Participants |
| Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) | Cure Rate for T. Trichiura (CR) by qPCR | 152 Participants |
| Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) | Cure Rate for T. Trichiura (CR) by qPCR | 188 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Cure Rates for for S. Stercoralis
For S. stercoralis, the cure rate is defined as the proportion of participants who test negative for S. stercoralis larvae in the Baermann tesi on day 21 post-treatment, relative to the total number of participants infected at baseline in Phase III (n=97).
Time frame: 21 days
Population: Intention to treat population infected with S. stercoralis from Phase III of the study (n=97).~A separate efficacy analysis by phase was not conducted, as the protocol specifies that the required sample size for this outcome is derived exclusively from participants infected with S. stercoralis at baseline in Phase III.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Albendazole | Cure Rates for for S. Stercoralis | 13 Participants |
| Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) | Cure Rates for for S. Stercoralis | 38 Participants |
| Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) | Cure Rates for for S. Stercoralis | 41 Participants |
Secondary
Egg Reduction Rate for Hookworm (ERR)
The Egg Reduction Rate (ERR) is defined as the percentage reduction in the geometric mean (GM) of eggs per gram (EPG) of feces from baseline to post-treatment.
Time frame: 21 days
Population: Intention to treat population infected with hookworm from Phase III of the study (n=350).~A separate efficacy analysis by phase was not conducted, as the protocol specifies that the required sample size for this outcome is derived exclusively from participants infected with hookworms at baseline in Phase III.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Albendazole | Egg Reduction Rate for Hookworm (ERR) | 97.8 Percentage of reduction |
| Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) | Egg Reduction Rate for Hookworm (ERR) | 99.0 Percentage of reduction |
| Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) | Egg Reduction Rate for Hookworm (ERR) | 99.8 Percentage of reduction |
Secondary
Egg Reduction Rate for T. Trichiura (ERR)
The Egg Reduction Rate (ERR) is defined as the percentage reduction in the geometric mean (GM) of eggs per gram (EPG) of feces from baseline to post-treatment.
Time frame: 21 days
Population: Intention to treat population infected with Trichuris trichiura from both Phase II and Phase III of the study (n=636).~A separate efficacy analysis by phase was not conducted, as the protocol specifies that the required sample size for this outcome is derived from all participants infected with T. trichiura at baseline, combining those from Phase II and Phase III.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Albendazole | Egg Reduction Rate for T. Trichiura (ERR) | 83.4 Percentage of reduction |
| Single Dose Albendazole-Ivermectin Fixed Dose Co-formulation (FDCx1) | Egg Reduction Rate for T. Trichiura (ERR) | 99.2 Percentage of reduction |
| Daily Dose of Albendazole-Ivermectin FIxed Dose Co-formulation for Three Consecutive Days (FDCx3) | Egg Reduction Rate for T. Trichiura (ERR) | 99.9 Percentage of reduction |
Secondary
To Evaluate the Frequency of Known ALB Resistant Alleles in Hookworm and T. Trichiura in the Three Treatment Arms Before and After Treatment.
The original objective as per the protocol was to To evaluate the frequency of known ALB resistant alleles in hookworm and T. trichiura in the three treatment arms before and after treatment with the endpoint being Evaluation of genotypic albendazole resistance in the three arms. This objective was based on the hypothesis that mutations at codons 167, 198, and 200 of the beta-tubulin gene of Trichuris trichiura were associated with resistance. However, since this time, it has become increasingly evident, based on research from us (PMID: 35895348, 39546832, 34563247) and others, that this hypothesis is no longer supported, and that the genetic determinants of resistance in T. trichiura are yet to be discovered. Therefore, we have begun evaluating, using whole genome sequencing, other genetic variants and their association with poor treatment response. This research is exploratory and ongoing. Therefore, the original outcome as defined in the protocol could not be assessed.
Time frame: 21 days
Population: Although samples were collected from participants, they were not analyzed and will not be analyzed in the future, as emerging scientific evidence has invalidated the hypothesis.