Table 2 Examples of microbiome-based therapies (non-genetically modified) at clinical stage (current or more recent phase)
Delivery | Product | Indication | Primary outcome | Current phase | Study status | Clinical trial ID | Reference Pubmed ID (when available) | |
|---|---|---|---|---|---|---|---|---|
Products derived from donor feces | Oral capsule | Seres Therapeutics, SER-109 (VOWST®) | Reduction of Recurrence of Clostridioides difficile Infection (CDI) | Superiority of SER-109 as compared with placebo in reducing the risk of CDI recurrence up to 8 weeks after dosing. | III | Completed studies | NCT03183128 | Feuerstadt et al.N Engl J Med. 2022 PMID: 35045228 |
Liquid suspension (enema, colonoscopy or upper GI administration) | Biomebank, Biomictra | Recurrent Clostridioides difficile infection (CDI) | Not available | |||||
Enema | Rebiotix, RBX2660 (Rebyota®) | Preventing recurrent episodes of Clostridioides difficile Infection (CDI) | Absence of CDI diarrhea for 8 weeks after study treatment. | III | Completed studies | NCT03244644 | Khanna et al. Drugs. 2022 PMID: 36287379 | |
Oral capsule | Finch, CP-101 | Prevention of Recurrent Clostridioides difficile Infection (CDI) | CDI recurrence through 8 weeks. | III | Terminated study | NCT05153499 | ||
Enema | MaatPharma, MaaT013 | Steroid Refractory Graft Versus Host Disease (GvHD) | Overall response rate of gastrointestinal-acuteGvHD at Day 28. | III | On-going study | NCT04769895 | ||
Oral capsule | MaatPharma, MaaT033 | Hematological malignant patients under intensive chemotherapy | Evaluation of safety and tolerability of MaaT033 in patients with hematologic malignancies up to 10 weeks. | Ib | Completed study | NCT04150393 | ||
Oral capsule | MaatPharma, MaaT033 | Prevention of allogeneic Hematopoietic Cell Transplantation (HCT) complications | Comparison of the efficacy of Maat033 with its placebo on overall survival at 12 months after alloHCT. | IIb | On-going study | NCT05762211 | ||
Products derived from donor cervico-vaginal secretions | Vaginal administration | Freya Biosciences, FB101 | Vaginal dysbiosis | Changes in relative abundance of vaginal lactobacilli species. | I | Completed | NCT05850078 | |
Rationally-designed bacterial consortium | Oral treatment | MRM Health, MH002 | Ulcerative colitis | Safety and tolerability of MH002 in subjects with mild to moderate ulcerative colitis. | IIa | Completed study | EudraCT Number: 2020-004355-33 | |
Multiple strains LBP | Oral capsule | Biomica, BMC 128 in combination with nivolumab (immunotherapy) | Non-small Cell Lung Cancer, Melanoma or Renal Cell Carcinoma | Safety and tolerability assessments (through study completion, an average of 1 year) | I | On-going study | NCT05354102 | |
Oral capsule | Vedenta, VE-303 | Prevention of Recurrent Clostridioides difficile Infection | Percentage of participants with toxin-positive, laboratory-confirmed, or clinically diagnosed and treated CDI recurrence before or at Week 8 (i.e., 8 weeks after the first dose of study treatment). | II | Completed studies | NCT03788434 | Louie et al. JAMA. 2023 PMID: 37060545 | |
Oral capsule | Vedenta, VE-303 | Prevention of Recurrent Clostridioides difficile Infection | Proportion of participants with laboratory-confirmed CDI recurrence before or at Week 8. | III | On-going study | NCT06237452 | ||
Oral capsule | Vedenta, VE-202 | Mild-to-Moderate Ulcerative Colitis | Proportion of participants with endoscopic response on flexible sigmoidoscopy after 8 weeks of treatment with VE202 or placebo. | II | On-going study | NCT05370885 | ||
Oral administration | Vedenta, VE-416 | Food allergy | Number of participants with treatment-related adverse events (Phase I) The geometric mean of the maximum tolerated dose of peanut protein at DBPCFC (Double-blind, placebo-controlled food challenge - Phase II) | I/II | On-going study | NCT03936998 | ||
Oral administration | Vedenta, VE-800 in combination with nivolumab (immunotherapy) | Advanced or Metastatic Cancer | Safety and tolerability of VE800 in combination with nivolumab: Number of Participants with Adverse Events from the first dose to the last dose (up to 56.7 weeks), plus 100 days of post-treatment follow-up. | I/II | Completed study | NCT04208958 | ||
Oral administration | Seres Therapeutics, Ser-401 in combination with nivolumab (immunotherapy) | Cancer | Percentage of patients with adverse events up to 2 years | Ib | Completed study | NCT03817125 | Glitza et al. Cancer Discov. 2024 PMID: 38588588 | |
Oral administration | Seres Therapeutics, Ser-155 | Reduction of the risk of infection and Graft vs. Host Disease (GvHD) in Adults Undergoing Hematopoietic Stem Cell Transplantation (HSCT) | Safety and tolerability of SER-155, including incidence and severity of adverse events, serious adverse events, or adverse events of special interest (Day 100) | Ib | On-going study | NCT04995653 | ||
Oral capsule | NuBiyota, MET-2 | Recurrent Clostridioides difficile Infection (CDI) | Clinical resolution of diarrhea with no CDI relapse at 30 days following the last dose of MET-2. | I | Completed | NCT02865616 | Kao et al. Lancet Gastroenterol Hepatol. 2021 PMID: 33631102 | |
Oral capsule | NuBiyota, MET-4 in combination with immunotherapy | Cancer | Cumulative relative abundance of immunotherapy-responsiveness associated species at day 12 of MET-4 | III | On-going study | NCT03686202 | ||
Mucoadhesive vaginal pills | LC106 and LC115 (Lactobacillus crispatus) | Prevention of recurrent bacterial vaginosis | Detection of any one strain from the LBP at 5% relative abundance or greater, or any combination of strains at 10% relative abundance or greater using shotgun metagenomic sequencing over 5 weeks. | I | On-going study | NCT06135974 | ||
Vaginal capsule | Freya Biosciences, FB301 | Women infertility | Safety, tolerability of single and multiple dosing; change in vaginal microbiome. | I | On-going Study | EudraCT Number: 2024-517539-38 | ||
Single strain LBP | Oral suspension | Infant Bacterial Therapeutics (IBT) IBP-9414 (Limosilactobacillus reuteri) | Prevention of Necrotizing Enterocolitis | Confirmed necrotizing enterocolitis (NEC) and time to sustained feeding tolerance from the first dose until the infant reaches 34 weeks + 6 days post-menstrual age. | III | On-going study | NCT03978000 | |
Oral capsule | OxThera, Oxabact® OC5 (Oxalobacter formigenes) | Primary Hyperoxaluria | Change from baseline in plasma oxalate concentration after 52 weeks of treatment. | III | Completed study, Primary endpoint was nearly achieved (p = 0.06)a | NCT03116685 | ||
Oral capsule | 4D Pharma, Blautix (Blautia hydrogenotrophica) | Irritable bowel syndrome (IBS) | Percentage of participants with overall response (from baseline up to week 8). | II | Completed study, Significant increase in overall response at week 8 (24.1% in active group versus 17.5% in placebo)b | NCT03721107 | ||
Oral liquid | Destiny Pharma, NTCD-M3c (Non-toxigenic C. difficile M3 strain) | Prevention of recurrence of C. difficile infection | Number of participants with treatment-emergent adverse events and serious adverse events from baseline up to 7 days after the last dose of study drug (up to Week 3). | II | Completed study, Significant reduction in recurrence of C. difficile infection compared to placebo (5% in optimal dose regimen v 30% in placebo group) | NCT01259726 | Gerding et al. JAMA. 2015 PMID: 25942722 | |
Oral capsule | Biogaia Pharma, BGP345A (Lactobacillus gasseri) | Constipation due to opioid-based medications | Change in the average weekly number of spontaneous bowel movements (expressed in number of stools/week) over the 4 week treatment period. | II | On-going study | NCT05133076 | ||
Oral capsule | Biogaia Pharma, BGP-014 (Limosilactobacillus reuteri) | Ulcerative colitis | Safety and tolerability of BGP-014 up to 10 weeks. | I/II | On-going study | NCT05118919 | ||
Oral capsule | 4D Pharma, MRx0518 in combination with pembrolizumab (Enterococcus gallinarum) | Solid tumors | Safety and tolerability of MRx0518 in combination with pembrolizumab; preliminary evidence of anti-tumor activity. Time frame: baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days) | I/II | Terminated study | NCT03637803 | ||
Oral capsule | Ysopia, Xla1 (Christensenella minuta) | Obesity | To assess the safety and tolerability of Xla1 in healthy adult volunteers [part 1], and, subsequently, in overweight and class I obese adults [part 2]. | I | Completed study, Significant reduction of LDL-cholesterol at week 16 d | NCT04663139 | ||
Oral capsule | Genome & Company, GEN-001 in combination with avelumab (Lactococcus lactis) | Solid tumors | Incidence of adverse events (1 year), laboratory abnormalities (1 year) and dose-limiting toxicity (28 days). Objective response (OR) of GEN-001 in patients with advanced or metastatic solid tumors, when administered as combined with avelumab (2 years) | I | Completed study | NCT04601402 | ||
Oral capsule | Adiso Therapeutics, ADS024e (LPA3 agonist-producing Bacillus velezensis) | Prevention of recurrence of C. difficile infection | Safety and tolerability of ART24 based on the percentage of subjects experiencing treatment-emergent adverse events. Safety and tolerability of ART24 based on the number of subjects observed with a change from baseline in clinical laboratory tests, vital signs, physical examination. | I | Completed study | NCT04891965 | ||
Oral capsule | Exeliom Biosciences, EXL01 (Faecalibacterium prausnitzii) | Maintenance of steroid-induced clinical response/ remission in participants with mild to moderate Crohn’s disease | Systemic and intestinal safety and tolerability of orally administered EXL01 up to 43 weeks. | I | On-going study | NCT05542355 EudraCT Number: 2021-003432-81 | ||
Oral administration | Scioto Biosciences, SB-121, (Limosilactobacillus reuteri with Sephadex® and Maltose) | Autistic disorder | Adverse event of special interest and adverse events leading to discontinuation. | I | Completed study | NCT04944901 | Schmitt et al. Sci Rep. 2023 PMID: 36997569 | |
Oral administration (sachet) | Osel, CBM588, in combination with nivolumab and ipilimumab (Clostridium butyricum) | Metastatic renal cell carcinoma | Change in Bifidobacterium composition of stool (from baseline up to week 12). | I | Completed study | NCT03829111 | Dizman et al. Nat Med. 2022 PMID: 35228755 | |
Vaginal administration | Osel, Lactin-V (Lactobacillus crispatus CTV-05) | Pregnant women at high-risk of preterm birth | The number of participants that demonstrate a change in vaginal colonisation during and following LACTIN-V use (2-4 years). | I | Completed study | NCT03992534 | Bayar et al. Benef Microbes. 2023 PMID: 36815494 | |
Oral capsule | MoonBiotech, MNC-168 (Enterococcus strain MNC-168) | Advanced Malignant Solid Tumors | Safety evaluated by The National Cancer Institute Common Terminology Criteria for Adverse Events. | I | Ongoing study | NCT05383703 | ||
Oral capsule | Microba, MAP315 | Ulcerative colitis | Safety, tolerability and pharmacokinetics of MAP 315 in 32 healthy adults. | I | Completed study | ACTRN12623000291684 | ||
Non-living biotherapeutic products | Intradermal injection | Immodulon, IMM101 (heat killed Mycobacterium obuense) in combination with checkpoint inhibitor therapy | Advanced Melanoma | Incidence, frequency and severity of treatment emergent adverse events throughout the study. | II | Completed study | NCT03711188 | |
Phage therapy-based medicinal products | Oral liquid | Intralytic Inc, EcoActive | Level of intestinal Adherent Invasive Escherichia coli (AIEC) in patients with inactive Crohn’s disease (CD) | Incidence of adverse events, severity of adverse events, effect on Harvey Bradshaw Index, effect on inflammation as indicated by C-reactive protein and fecal calprotectin (up to 6 months) | I/IIa | Ongoing study | NCT03808103 |
