Trial Outcomes & Findings for Phase 2 Trial of LACTIN-V in Women at High Risk of HIV Acquisition (NCT NCT05022212)
NCT ID: NCT05022212
Last Updated: 2024-08-13
Results Overview
The proportion of participants with decreased genital tract proinflammatory cytokines and HIV target cells over 64 days of follow up, compared to levels at baseline. The outcome will be a change in immune parameters after treatment with LACTIN-V in comparison to placebo (proinflammatory cytokines in genital fluid, activated endocervical HIV target cells and the anti-HIV effect of vaginal secretions), measured as the number and proportions of endocervical CD4+ HIV target cells (i.e., CD4+/CCR5+/HLA-DR+/CD38+ T cells) at Day 64. Decreased inflammation will be defined using a measure of \>1 log10 decrease in 3/8 markers between baseline and Day 64.
COMPLETED
PHASE2
45 participants
over 64 days
2024-08-13
Participant Flow
45 were randomized to study product. 8 became then ineligible for randomization for the following reasons: * Not completing metronidazole course (n=1) * Acute UTI, STD, or vaginal infection besides BV (n=2) * Any condition requiring use of systemic antibiotics during the trial (n=2) * floods impacting on site access (n=2) * site disruption because of social unrest (n=1)
Participant milestones
| Measure |
LACTIN-V
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator.
Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
LACTIN-V: administered vaginally
|
Placebo
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation.
Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Placebo: administered vaginally
|
|---|---|---|
|
Overall Study
STARTED
|
32
|
13
|
|
Overall Study
COMPLETED
|
32
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
LACTIN-V
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator.
Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
LACTIN-V: administered vaginally
|
Placebo
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation.
Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Placebo: administered vaginally
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
Baseline Characteristics
Phase 2 Trial of LACTIN-V in Women at High Risk of HIV Acquisition
Baseline characteristics by cohort
| Measure |
LACTIN-V
n=32 Participants
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator.
Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
LACTIN-V: administered vaginally
|
Placebo
n=13 Participants
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation.
Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Placebo: administered vaginally
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
32 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
32 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
|
Region of Enrollment
South Africa
|
32 participants
n=5 Participants
|
13 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Vaginal Gram Stain with Nugent Score 4-10
|
32 participants
n=5 Participants
|
13 participants
n=7 Participants
|
45 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: over 64 daysPopulation: Available samples at baseline and Day 64: LACTIN-V n=30, Placebo n=11. The comparison of the LACTIN-V vs. placebo arms was performed on a modified Intent to Treat (mITT) population, excluding one placebo participant who was erroneously dispensed two doses of LACTIN-V. Additionally, missing samples at Day 64 from two participants in the LACTIN-V group and one participant in the placebo group.
The proportion of participants with decreased genital tract proinflammatory cytokines and HIV target cells over 64 days of follow up, compared to levels at baseline. The outcome will be a change in immune parameters after treatment with LACTIN-V in comparison to placebo (proinflammatory cytokines in genital fluid, activated endocervical HIV target cells and the anti-HIV effect of vaginal secretions), measured as the number and proportions of endocervical CD4+ HIV target cells (i.e., CD4+/CCR5+/HLA-DR+/CD38+ T cells) at Day 64. Decreased inflammation will be defined using a measure of \>1 log10 decrease in 3/8 markers between baseline and Day 64.
Outcome measures
| Measure |
LACTIN-V
n=30 Participants
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator.
Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
LACTIN-V: administered vaginally
|
Placebo
n=11 Participants
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation.
Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Placebo: administered vaginally
|
|---|---|---|
|
Number of Participants With Genital Tract Inflammation
|
3 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: over 64 daysPopulation: The comparison of the LACTIN-V vs. placebo arms was performed on a modified Intent to Treat (mITT) population, excluding one placebo participant who was erroneously dispensed two doses of LACTIN-V. Available samples at Day 36: LACTIN-V n=32, Placebo n=12. Available samples at Day 64: LACTIN-V n=31, Placebo n=11.
The proportion of participants with Lactobacillus-dominant vaginal microbiota in young South African women. Measured will be dominance of Lactobacillus crispatus (defined as \> 50% relative abundance) after the intervention. Our primary outcome is measured at Day 36 (after 4 weeks of treatment with LACTIN-V), and at Day 64 (following the post- dosing phase).
Outcome measures
| Measure |
LACTIN-V
n=32 Participants
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator.
Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
LACTIN-V: administered vaginally
|
Placebo
n=12 Participants
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation.
Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Placebo: administered vaginally
|
|---|---|---|
|
Number of Participants With Lactobacillus-dominant Vaginal Microbiota
L. crispatus dominant vaginal bacterial community (> 50% relative abundance) on Day 36
|
13 Participants
|
0 Participants
|
|
Number of Participants With Lactobacillus-dominant Vaginal Microbiota
L. crispatus dominant vaginal bacterial community (> 50% relative abundance) on Day 64
|
8 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: over 64 daysPopulation: The comparison of the LACTIN-V vs. placebo arms was performed on a modified Intent to Treat (mITT) population, excluding one placebo participant who was erroneously dispensed two doses of LACTIN-V. Additionally, at Day 64 a missing sample from one participant in the placebo group. Available samples at Day 36: LACTIN-V n=32, Placebo n=12. Available samples at Day 64: LACTIN-V n=32, Placebo n=11.
The proportion of participants experiencing successful colonization with L. crispatus CTV-05 following dose of study product through the final visit (Day 64) in the LACTIN-V arm. This primary outcome is measured at Day 36 (after 4 weeks of treatment with LACTIN-V), and at Day 64 (following the post- dosing phase).
Outcome measures
| Measure |
LACTIN-V
n=32 Participants
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator.
Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
LACTIN-V: administered vaginally
|
Placebo
n=12 Participants
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation.
Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Placebo: administered vaginally
|
|---|---|---|
|
Number of Participants With Vaginal Colonization of L. Crispatus CTV-05
Detection of L. crispatus CTV-05 at Day 36
|
22 Participants
|
1 Participants
|
|
Number of Participants With Vaginal Colonization of L. Crispatus CTV-05
Detection of L. crispatus CTV-05 at Day 64
|
15 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: over 64 daysPopulation: The comparison of the LACTIN-V vs. placebo arms was performed on a modified Intent to Treat (mITT) population, excluding one placebo participant who was erroneously dispensed two doses of LACTIN-V. Additionally, at Day 36 a missing sample from one participant in the LACTIN-V group. Available samples at Day 36: LACTIN-V n=31, Placebo n=12. Available samples at Day 64: LACTIN-V n=32, Placebo n=12.
The proportion of participants with a positive test for vaginal dysbiosis (Nugent Score 4-10 on vaginal Gram Stain) in each study arm by Day 36 and Day 64. The Nugent Score has values from 0 -10. 0-3 describes an optimal vaginal microbiome with lactobacilli but little bacterial diversity, 4-6 is an intermediate score, and 7-10 characterizes a vaginal microbiome with few lactobacilli and an overgrowth of pathogens.
Outcome measures
| Measure |
LACTIN-V
n=32 Participants
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator.
Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
LACTIN-V: administered vaginally
|
Placebo
n=12 Participants
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation.
Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Placebo: administered vaginally
|
|---|---|---|
|
Number of Participants With Vaginal Dysbiosis Indicated by a Nugent Score 4-10 on Vaginal Gram Stain
Nugent Score 4-10 on Vaginal Gram Stain at Day 36
|
12 Participants
|
6 Participants
|
|
Number of Participants With Vaginal Dysbiosis Indicated by a Nugent Score 4-10 on Vaginal Gram Stain
Nugent Score 4-10 on Vaginal Gram Stain at Day 64
|
15 Participants
|
6 Participants
|
PRIMARY outcome
Timeframe: over 64 daysPopulation: All 45 participants are included in the safety analysis.
Overall Safety of LACTIN-V and the applicator will be measured by the proportion of participants reporting any solicited Adverse Events (AEs) through the final visit on Day 64, compared between study arms.
Outcome measures
| Measure |
LACTIN-V
n=32 Participants
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator.
Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
LACTIN-V: administered vaginally
|
Placebo
n=13 Participants
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation.
Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Placebo: administered vaginally
|
|---|---|---|
|
Number of Participants Reporting Any Solicited Adverse Events (AEs) Through the Final Visit
|
26 Participants
|
9 Participants
|
PRIMARY outcome
Timeframe: over 36 daysPopulation: Available acceptability data at Day 36: LACTIN-V n=30, Placebo n=13. Missing data from two participants in the LACTIN-V group.
Acceptability of LACTIN-V and the applicator will be measured by standardized questionnaire about acceptability of the study product and participants' stated willingness to use this type of product in the future, in each study arm. (Question "I would use the product again", on Day 36)
Outcome measures
| Measure |
LACTIN-V
n=30 Participants
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator.
Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
LACTIN-V: administered vaginally
|
Placebo
n=13 Participants
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation.
Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Placebo: administered vaginally
|
|---|---|---|
|
Number of Participants Willing to Use This Type of Product in the Future
neutral
|
5 Participants
|
3 Participants
|
|
Number of Participants Willing to Use This Type of Product in the Future
strongly agree
|
11 Participants
|
3 Participants
|
|
Number of Participants Willing to Use This Type of Product in the Future
agree
|
11 Participants
|
7 Participants
|
|
Number of Participants Willing to Use This Type of Product in the Future
disagree
|
2 Participants
|
0 Participants
|
|
Number of Participants Willing to Use This Type of Product in the Future
strongly disagree
|
1 Participants
|
0 Participants
|
Adverse Events
LACTIN-V
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LACTIN-V
n=32 participants at risk
LACTIN-V contains a naturally occurring human vaginal strain of Lactobacillus (L.) crispatus CTV- 05. At a potency of 2 x 109 cfu/dose, it is preserved in powder formulation, and applied by a vaginal applicator.
Women will receive the study product for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
LACTIN-V: administered vaginally
|
Placebo
n=13 participants at risk
A matching placebo formulation without L. crispatus CTV-05 is supplied in an identical applicator containing just the powder formulation.
Women will receive the placebo for five consecutive days, followed by twice weekly for three additional weeks. Women will be followed during the dosing (4 weeks) and post-dosing phase (4 weeks) for a total of 64 days.
Placebo: administered vaginally
|
|---|---|---|
|
Reproductive system and breast disorders
Abnormal vaginal discharge
|
28.1%
9/32 • 64 days
|
15.4%
2/13 • 64 days
|
|
Reproductive system and breast disorders
Abnormal vaginal odor
|
9.4%
3/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Reproductive system and breast disorders
external genital irritiation
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Reproductive system and breast disorders
external genital swelling
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Reproductive system and breast disorders
genital itching or burning
|
25.0%
8/32 • 64 days
|
30.8%
4/13 • 64 days
|
|
Reproductive system and breast disorders
vaginal bleeding other than menstruation
|
56.2%
18/32 • 64 days
|
38.5%
5/13 • 64 days
|
|
Reproductive system and breast disorders
abdominal pain / cramps
|
18.8%
6/32 • 64 days
|
7.7%
1/13 • 64 days
|
|
Gastrointestinal disorders
constipation
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Gastrointestinal disorders
diarrhea
|
3.1%
1/32 • 64 days
|
7.7%
1/13 • 64 days
|
|
Renal and urinary disorders
frequent urination
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Nervous system disorders
headache
|
6.2%
2/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
General disorders
nausea
|
6.2%
2/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Renal and urinary disorders
pain/ burning with urination
|
0.00%
0/32 • 64 days
|
15.4%
2/13 • 64 days
|
|
General disorders
vomiting
|
0.00%
0/32 • 64 days
|
7.7%
1/13 • 64 days
|
|
Reproductive system and breast disorders
abnormal discharge
|
6.2%
2/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Renal and urinary disorders
urine odor
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Gastrointestinal disorders
toothache
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Infections and infestations
pustule
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Infections and infestations
folliculitis
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
General disorders
chest discomfort
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Infections and infestations
eye infection, viral
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Infections and infestations
viral skin infection
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Skin and subcutaneous tissue disorders
papular rash
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Nervous system disorders
dizziness
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Reproductive system and breast disorders
genital ulceration
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Infections and infestations
chlamydial infection
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Respiratory, thoracic and mediastinal disorders
nasal congestion
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
|
Infections and infestations
subcutaneous abscess
|
3.1%
1/32 • 64 days
|
0.00%
0/13 • 64 days
|
Additional Information
Dr Anke Hemmerling, Co-Investigator
University of California, San Francisco
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place