Phase 2 Placebo-controlled Randomized Trial of LACTIN-V (Lactobacillus Crispatus CTV-05) Among Women at High Risk of HIV Acquisition in Durban, South Africa

The purpose of this study is to assess the impact of LACTIN-V, a vaginally administered live biotherapeutic product (LBP) that contains the human L. crispatus CTV-05 strain, on the vaginal microbiome of Lactobacillus-deficient young women in the South African FRESH study who are at high risk for HIV acquisition.

Start Date10 May 2021

Sponsor / Collaborator

The University of California, San Francisco

[+5]

NCT03992534 / Unknown statusPhase 1IIT

Feasibility, Safety, Tolerance and Assessment of LACTIN-V Use in a Cohort of Pregnant Women at Risk of Preterm Birth

Preterm birth (PTB) is the primary cause of infant death worldwide. It has been shown that a vaginal microbiota deplete in Lactobacillus species is a risk factor for preterm labour. Conversely a vaginal microbiota dominated by Lactobacillus crispatus appears to be protective for these adverse outcomes. A wide range of 'over the counter' Lactobacillus spp. containing products targeted at 'vaginal health' and formulated for vaginal administration are available, but most of them do not contain vaginal species of Lactobacillus. The primary aim of this study is to determine whether vaginal supplementation with L. crispatus CTV-05 is associated with colonisation.

Start Date16 Sep 2019

Sponsor / Collaborator

Imperial College London

[+1]

NCT02766023 / CompletedPhase 2IIT

Phase II-b Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus Crispatus CTV-05 (LACTIN-V) to Prevent the Recurrence of Bacterial Vaginosis

This Phase 2b trial is designed to provide a screening evaluation for the hypothesis that, following a 5-day treatment with MetroGel® to treat BV, L. crispatus CTV-05 (LACTIN-V, Osel, Inc.) administered at 2 x 10^9 cfu/dose using a vaginal applicator reduces the 12-week incidence of BV recurrence when compared to placebo. The primary objectives of this study are: 1) To estimate the efficacy of repeated doses of LACTIN-V (2 x 10^9 cfu/dose) as compared to placebo in preventing BV recurrence by 12 weeks following treatment of BV with MetroGel vaginal gel (MetroGel). 2) To assess the safety of LACTIN-V over 24 weeks by comparing the incidence of AEs between individuals randomized to LACTIN-V or placebo.

Start Date03 Jun 2016

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

100 Clinical Results associated with CTV-05

100 Translational Medicine associated with CTV-05

100 Patents (Medical) associated with CTV-05

Literatures (Medical) associated with CTV-05

06 Aug 2024·Microbiology Spectrum

Vaginal fungi are associated with treatment-induced shifts in the vaginal microbiota and with a distinct genital immune profile

Article

Author: Liu, Rachel ; Cohen, Craig R ; Huibner, Sanja ; Hemmerling, Anke ; Castañeda, Gloria R ; Coburn, Bryan ; Miller, Steve ; Kaul, Rupert ; Kulikova, Maria ; Armstrong, Eric ; Crawford, Emily

ABSTRACT Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a Lactobacillus crispatus -based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted P = 0.0006), with most of this increase attributable to Candida albicans . Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with Lactobacillus species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with Lactobacillus species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes. IMPORTANCE Vaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as Candida albicans . Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.

01 Jun 2024·Sexually Transmitted Diseases

Response to Antibiotic Treatment of Bacterial Vaginosis Predicts the Effectiveness of LACTIN-V (Lactobacillus crispatus CTV-05) in the Prevention of Recurrent Disease

Article

Author: Cohen, Craig R. ; Armstrong, Eric ; Hemmerling, Anke ; Wierzbicki, Michael R.

ObjectivesLive biotherapeutic products (LBPs) containing vaginal Lactobacillus crispatus are promising adjuvant treatments to prevent recurrent bacterial vaginosis (BV) but may depend on the success of initial antibiotic treatment.MethodsA post hoc analysis of data collected during the phase 2b LACTIN-V randomized control trial (L. crispatus CTV-05) explored the impact of clinical BV cure defined as Amsel criteria 0 of 3 (excluding pH, per 2019 Food and Drug Administration guidance) 2 days after completion of treatment with vaginal metronidazole gel on the effectiveness of an 11-week LACTIN-V dosing regimen to prevent BV recurrence by 12 and 24 weeks.ResultsAt enrollment, 88% of participants had achieved postantibiotic clinical BV cure. The effect of LACTIN-V on BV recurrence compared with placebo differed by initial clinical BV cure status. The LACTIN-V to placebo risk ratio of BV recurrence by 12 weeks was 0.56 (95% confidence interval, 0.35–0.77) among participants with initial clinical BV cure after metronidazole treatment and 1.34 (95% confidence interval, 0.47–2.23) among participants without postantibiotic clinical BV cure. Among women receiving LACTIN-V, those who had achieved postantibiotic clinical BV cure at enrollment reached higher levels of detectable L. crispatus CTV-05 compared with women failing to achieve postantibiotic clinical BV cure.ConclusionsLACTIN-V seems to only decrease BV recurrence in women with clinical cure of BV after initial antibiotic treatment. Future trials of LBPs should consider limiting enrollment to these women.

14 Apr 2023·Beneficial Microbes

Impact of Lactobacillus crispatus-containing oral and vaginal probiotics on vaginal health: a randomised double-blind placebo controlled clinical trial

Article

Author: Smidt, I ; Saare, M ; Le, D D ; Piiskop, S ; Ausmees, K ; Jaagura, M ; Kõljalg, S ; Štšepetova, J ; Salumets, A ; Mändar, R ; Rööp, T ; Tamm, H ; Sõerunurk, G

Health of reproductive tract is tightly associated with balance of microbial communities in this area. Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) represent common disturbances of vaginal communities. Vaginal discharge due to BV or VVC is a very frequent reason for visiting gynaecologist. We aimed to evaluate the impact of the novel evidence-based probiotics on BV and VVC patients. The study group included 89 BV and 93 VVC patients (aged 18-50 years) who were recruited into randomised double-blind placebo-controlled two-arm parallel trial. The patients of each diagnosis group received oral or vaginal probiotic capsules, or placebo capsules during 3 months. A probiotic capsule contained two (DSM32717 and DSM32720, in case of BV) or three (DSM32720, DSM32718 and DSM32716, in case of VVC) Lactobacillus crispatus strains. Vaginal, intestinal and general health was monitored weekly by questionnaire. Blood analyses were done in the beginning and at the end of trial. Vaginal samples were collected monthly, microscopic and molecular analyses were performed. The study revealed that both oral and vaginal capsules reduced the signs and symptoms in BV patients. Remarkable improvement was noted in Nugent score, amount and smell of discharge, but also in itching/irritation. Consumption of vaginal probiotics significantly increased the lactobacilli counts in their vagina while mean proportion of some BV-related bacteria decreased. In VVC patients, both oral and vaginal capsules lowered the combined score of two most important symptoms, amount of discharge and itching/irritation. In conclusion, the novel formulations of evidence-based well-focused probiotic L. crispatus strains are effective against BV and VVC being suitable for both vaginal and oral administration.Clinical trial registration: ISRCTN34840624, BioMed Central

News (Medical) associated with CTV-05

09 Sep 2024

·www.pharmaceutical-technology.com

EASD24: PolTREG’s T-cell therapy shows long-term remission in type 1 diabetes

PolTREG plans to start a pivotal Phase II/III trial of PTG-007 for the treatment of type 1 diabetes and is pursuing partnership funding. Image Credit: Anatoliy Cherkas / Shutterstock. PolTREG’s has presented positive long-term data for its cell therapy, PTG-007, showing that the therapy induced clinical remission for type 1 diabetes for up to 12 years. The follow-up data from 54 patients with early-onset type 1 diabetes who took part in Phase I and II trials was presented at the European Association for the Study of Diabetes (EASD) taking place from 9-13 September in Spain. In light of the positive data, the Polish company will start a pivotal Phase II/III trial of PTG-007 for the treatment of type 1 diabetes and is pursuing partnership funding. “Today’s results are extremely encouraging and show that some patients remain in clinical remission for up to 12 years after initial treatment,” said Professor Piotr Trzonkowski, PolTREG’s CEO. “This makes us very eager to launch a pivotal study of PTG-007 as soon as we find a suitable partner.” The 54 patients with early-onset type 1 diabetes were followed for 7-12 years after receiving initial treatment as part of Phase I and Phase II trials. The study showed that a “proportion of patients” remained insulin-independent up to 18 to 24 months after treatment. See Also: LACTIN-V by Osel for Human Papillomavirus Infections: Likelihood of Approval Cadisegliatin by VTv Therapeutics for Type 1 Diabetes (Juvenile Diabetes): Likelihood of Approval Additionally, some of the patients remained in clinical remission for 7-12 years after being treated with PTG-007. The trial defined clinical remission as having a low need for external insulin, while retaining proper metabolic/glycaemia control. The study also found that the “best results” were seen in patients who received the combination therapy of Treg therapy and Roche and Biogen ’s anti-CD20 treatment Rituxan (rituximab). The company plans to release detailed data and publish the results in a peer-reviewed scientific publication. PolTREG plans to initiate a Phase II trial evaluating PTG-007 in patients with presymptomatic type 1 diabetes. Cell therapies as a treatment for type 1 diabetes are gaining popularity. Last year saw the US Food and Drug Administration (FDA) approving the first cell therapy, CellTrans’s Lantidra (donislecel) for the treatment of type 1 diabetes. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

Cell TherapyClinical ResultPhase 1Phase 2Gene Therapy

09 Sep 2024

·www.pharmaceutical-technology.com

Epsilogen secures additional funds in Series B for cancer treatment

The funds will support the trial of MOv18 IgE to potentially treat platinum-resistant ovarian cancer. Credit: Jo Panuwat D/Shutterstock. Epsilogen has completed a Series B expansion financing round, raising £12.5m ($16.4m) to progress the development of its immunoglobulin E (IgE) antibodies for cancer treatment. The investment was sourced entirely from existing backers British Patient Capital, the Novartis Venture Fund, Epidarex Capital, the 3B Future Health Fund and ALSA Ventures. The latest funding takes the total raised in the Series B financing round to £43.25m. The funds will primarily support the clinical proof of concept for MOv18 IgE, the company’s leading asset, in a Phase Ib trial targeting platinum-resistant ovarian cancer. MOv18 IgE, a therapeutic IgE antibody, is designed to target the folate receptor alpha (FRα) which is prevalent in various cancers. See Also: LACTIN-V by Osel for Human Papillomavirus Infections: Likelihood of Approval Cadisegliatin by VTv Therapeutics for Type 1 Diabetes (Juvenile Diabetes): Likelihood of Approval The Phase Ib trial of MOv18 IgE will have dose escalation and expansion parts, enrolling patients with FRα-positive PROC who have undergone up to four previous treatments. The trial follows a Phase I study where MOv18 IgE showed safety, tolerability and initial signs of clinical activity. MOv18 IgE’s unique mechanism of action is different from that of other clinical agents, due to its high-affinity binding to FcεR1 that promotes immunosurveillance and robust tumour cell destruction by myeloid cells. IgE antibodies have the potential to alter the tumour immune microenvironment, making it more pro-inflammatory, which results in higher levels of activated T cells and macrophages within the tumour, enhancing its destruction. Established in 2017, Epsilogen is a spin-out from King’s College London, UK. Its CEO Tim Wilson stated: “We are delighted to have received strong continued support from our existing investors, and we thank them. “The promise of IgE to treat cancer is based upon its unique mechanism of action and MOv18 IgE is the first ever to be tested in man. Everything is ready for phase Ib initiation which will occur shortly and we look forward to reporting progress from the trial.”

Phase 1INDPhase 2Immunotherapy

09 Sep 2024

·www.pharmaceutical-technology.com

Sun Pharma and Moebius gain FDA fast track for osteoarthritis drug

In Phase IIb trial, the product provided substantial pain relief in osteoarthritis knee pain patients. Credit: VPLAB/Shutterstock. Sun Pharmaceutical Industries (Sun Pharma) and Moebius Medical have received fast track designation (FTD) from the US Food and Drug Administration (FDA) for MM-II (Large Liposomes of DPPC [dipalmitoylphosphatidylcholine] and DMPC [1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine]), a non-opioid treatment for osteoarthritis knee pain. Osteoarthritis is a common chronic joint disease marked by the deterioration of joint cartilage. The FTD aims to expedite the development and review of treatments for serious conditions with unmet medical needs. This programme will accelerate the availability of new medicines that could significantly improve patient outcomes. Sun Pharma and Moebius will benefit from more frequent communication with the FDA and the possibility of an expedited approval process. See Also: LACTIN-V by Osel for Human Papillomavirus Infections: Likelihood of Approval Cadisegliatin by VTv Therapeutics for Type 1 Diabetes (Juvenile Diabetes): Likelihood of Approval Moebius Medical CEO Moshe Weinstein stated: “This fast track designation, which will enable the FDA to review MM-II in an expedited manner, is an important milestone in the development of MM-II and follows our recently released Phase IIb data, which showed MM-II’s potential to provide effective and durable treatment for patients with knee pain of osteoarthritis.” MM-II is based on a technology involving large liposomes composed of DPPC and DMPC, designed to reduce joint friction and wear, thereby alleviating pain. The potential of MM-II was demonstrated in a Phase IIb clinical trial (NCT04506463), where a single 3ml intra-articular injection provided substantial pain relief compared to a placebo for up to 26 weeks. The companies are now preparing for confirmatory Phase III clinical trials to further evaluate the efficacy and safety of MM-II. Sun Pharma Global Development head and senior vice-president Marek Honczarenko stated: “As we enter Phase III development, we are very encouraged by the FDA’s decision to grant fast track designation to MM-II and recognise its potential to fill an unmet medical need for patients suffering from osteoarthritis.”

Phase 2Fast TrackClinical ResultPhase 3

100 Deals associated with CTV-05

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bacterial Vaginosis	Phase 3	US	Osel, Inc.	22 Jul 2022
HIV Infections	Phase 2	ZA	Osel, Inc.	10 May 2021
Obstetric Labor, Premature	Phase 1	US	Osel, Inc.	22 Jul 2022
Urinary Tract Infections	Preclinical	US	University of Washington	18 Aug 2015
Candidiasis	Preclinical	US	Osel, Inc.	31 Aug 2011
Female genital tract infection	Preclinical	US	The Medicines Co.	17 Aug 2000

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05022212 (CTgov)	Phase 2	HIV Infections \| Bacterial Vaginosis	45	LACTIN-V (LACTIN-V)	lmszsjpiyv(tlmzxajwxn) = kojeemfeif ctvjtssrwo (ipqudjkesq, bqmsetaljj - prpugpdwhc) View more	-	13 Aug 2024
				Placebo (Placebo)	lmszsjpiyv(tlmzxajwxn) = xjukoskidb ctvjtssrwo (ipqudjkesq, dqvkogxrbo - wpjfyhejcz) View more
NCT03151967 (CTgov)	Phase 2/3	Urinary Tract Infections	27	Lactobacillus crispatus CTV-05 (Applicator With LACTIN-V Treatment)	gkorrlgkti(vbhnmdnxcb) = agtbpmjyme yugeuibuag (xwcxkyphzd, arcgphfsel - lumkxtowqq) View more	-	01 Mar 2023
				Placebo (Applicator With Placebo)	gkorrlgkti(vbhnmdnxcb) = cumjkncgwu yugeuibuag (xwcxkyphzd, nhkyuytief - zjnxccseow) View more
NCT02766023 (Pubmed) Manual	Phase 2	Bacterial Vaginosis	228	Lactin-V	rlycrwdwib(ibafqcqrhw) = geahzmqolw bzlascnnpq (udpwipouts ) View more	Positive	14 May 2020
				Placebo	rlycrwdwib(ibafqcqrhw) = mhkkqffzps bzlascnnpq (udpwipouts )
NCT02766023 (CTgov)	Phase 2	Bacterial Vaginosis	228	Metronidazole+Lactobacillus crispatus CTV-05 (LACTIN-V)	tgbkygzofg(opydgsxncy) = kauxhhvbso qlfttfttbl (cargiyawva, gmahomgelm - deghaxexdy) View more	-	11 Feb 2020
				Placebo+Metronidazole (Placebo)	tgbkygzofg(opydgsxncy) = acpojblnhz qlfttfttbl (cargiyawva, bmifxebtic - jgacplkbbp) View more
NCT00305227 (CTgov)	Phase 2	Urinary Tract Infections	100	Lactin-V (Lactin-V)	uycmkgfgei(nbevgsteto) = dhgjofxywu ubyeeqbdph (envznbmrwg, dyaefdudpg - bzkmppgmos) View more	-	04 Jul 2014
				Placebo (Placebo)	uycmkgfgei(nbevgsteto) = ergzkovijy ubyeeqbdph (envznbmrwg, pudbuwexwp - uzjcpslopz) View more
NCT00305227 (Pubmed \| Clin Infect Dis)	Phase 2	Urinary Tract Infections	100	Lactin-V	riccynmvko(ofcscvwdbj) = aadfejrznw avawxzrntc (ponokqpgoj )	Positive	01 May 2011
				Lactobacillus crispatus probiotic (Placebo)	riccynmvko(ofcscvwdbj) = vsijmybjbq avawxzrntc (ponokqpgoj )

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