CNTY-101 for Lupus

(CALiPSO-1 Trial)

Recruiting at 5 trial locations

Overseen By Century Therapeutics Clinical Team

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Century Therapeutics, Inc.

Disqualifiers: Hemodialysis, CNS disease, Transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CNTY-101 to determine its safety and effectiveness for people with certain autoimmune diseases. The focus includes conditions like systemic lupus erythematosus (SLE), lupus nephritis (LN), idiopathic inflammatory myopathies (IIM), and diffuse cutaneous systemic sclerosis (DcSSc). Participants will receive the treatment in various ways to identify the optimal dose. This trial suits those who have struggled with these conditions and found other treatments unsuccessful. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive it.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants with diabetes or hypothyroidism should have stable medications for at least 4 weeks before screening, which suggests that some medications may need to be continued.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that CNTY-101 is under investigation for its safety and effectiveness in treating autoimmune diseases like systemic lupus erythematosus (SLE), lupus nephritis (LN), idiopathic inflammatory myopathies (IIM), and diffuse cutaneous systemic sclerosis (DcSSc). Earlier studies tested CNTY-101 in patients with similar conditions, such as B-cell lymphomas, and the results suggested it was generally safe.

Most patients in these studies tolerated CNTY-101 well, with no unexpected serious side effects. However, as this is a Phase 1 trial, the main goal is to assess safety and determine the right dose. While early results are promising, more research is needed to fully understand the treatment's safety in humans.

Participants in the current trial will receive CNTY-101 along with lymphodepleting chemotherapy (LDC) and may also receive interleukin 2 (IL-2), which is being tested to see if it enhances the treatment's effectiveness. This combination aims to increase effectiveness while closely monitoring for any side effects. Discuss any concerns with the trial team before participating. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

CNTY-101 is unique because it targets lupus in a new way by utilizing a specific combination of lymphodepleting chemotherapy and human recombinant interleukin 2 (IL-2) to enhance the immune response. Unlike standard treatments like corticosteroids and immunosuppressants, which broadly suppress the immune system to reduce inflammation, CNTY-101 aims to fine-tune the immune response with precision. This targeted approach could potentially lead to fewer side effects and more effective management of lupus symptoms, which is why researchers are excited about its potential.

What evidence suggests that this trial's treatments could be effective for lupus and other autoimmune diseases?

Research shows that CNTY-101, which participants in this trial may receive, targets and reduces harmful B cells to treat autoimmune diseases. In systemic lupus erythematosus (SLE), this treatment aims to calm the overactive immune system that harms tissues. Studies have shown a 73% success rate for early-stage treatments for SLE. For lupus nephritis (LN), another condition under study in this trial, research indicates an 84% chance of improvement in early trials. Although limited data exists for idiopathic inflammatory myopathies (IIM) and diffuse cutaneous systemic sclerosis (DcSSC), both also under study in this trial, CNTY-101’s focus on B cells offers hope, as these cells play a crucial role in these conditions. Overall, the treatment’s method suggests potential benefits for these autoimmune diseases. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for people with tough-to-treat B cell-mediated autoimmune diseases, like severe lupus. They should have a specific diagnosis of SLE for at least 6 months and active disease as shown by certain test scores. Those with stable diabetes or hypothyroidism can join if their condition has been under control for over a month.

Inclusion Criteria

I have been diagnosed with SLE for at least 6 months.

I have high levels of anti-dsDNA or anti-Smith antibodies.

My diabetes or thyroid condition is stable and I've been on the same medication for at least 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Confirmation Phase

Participants undergo lymphodepleting chemotherapy followed by administration of CNTY-101, administered 3 times over 3 weeks during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.

4 weeks

Dose Expansion Phase

Participants receive treatments using the recommended phase 2 regimen (RP2R) confirmed during Part 1.

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CNTY-101
• IL-2
• Lymphodepleting Chemotherapy

Trial Overview CALiPSO-1 is testing CNTY-101's safety and effectiveness in patients with refractory autoimmune conditions. It involves giving participants CNTY-101 along with IL-2 and lymphodepleting chemotherapy to see how well it works against severe symptoms of diseases like lupus.

How Is the Trial Designed?

Group I: Arm D: CNTY-101 in DcSSC Participants Experimental Treatment 3 Interventions

During Part 1 (Dose Confirmation Phase), participants with DcSSC will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2. After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2. During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.

Group II: Arm C: CNTY-101 in IIM Participants Experimental Treatment 3 Interventions

During Part 1 (Dose Confirmation Phase), participants with IIM will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2. After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2. During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.

Group III: Arm B: CNTY-101 in LN Participants Experimental Treatment 3 Interventions

During Part 1 (Dose Confirmation Phase), participants with LN will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2. After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2. During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.

Group IV: Arm A: CNTY-101 in SLE Participants Experimental Treatment 3 Interventions

During Part 1 (Dose Confirmation Phase), participants with SLE will undergo lymphodepleting chemotherapy (LDC) followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental human recombinant interleukin 2 (IL-2). After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2. During Part 2 (Dose Expansion Phase), participants will receive treatments using the recommended phase 2 regimen (RP2R) confirmed during Part 1.

Who Is Running the Clinical Trial?

Century Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

500+

Published Research Related to This Trial

Low-dose cyclophosphamide (LCYC) is an effective induction therapy for lupus nephritis, showing similar response rates to mycophenolate mofetil (MMF) and better than high-dose cyclophosphamide (HCYC) based on a meta-analysis of 11 randomized controlled trials involving 1212 patients.

LCYC also has the highest probability of reducing the risk of serious infections compared to MMF and HCYC, making it a safer option for patients undergoing treatment for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of low-dose and high-dose cyclophosphamide as induction therapy for lupus nephritis: a network meta-analysis. Bae, SC., Lee, YH.[2020]

The Lupus Multivariable Outcome Score (LuMOS) was developed using data from two pivotal trials of belimumab, demonstrating its ability to effectively measure treatment outcomes in systemic lupus erythematosus (SLE).

LuMOS showed significantly higher scores in patients treated with belimumab compared to placebo, outperforming the existing SLE Responder Index 4 (SRI-4) in distinguishing between responders and nonresponders, which could enhance future clinical trial analyses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Validation of a Novel Evidence-Based Lupus Multivariable Outcome Score for Clinical Trials. Abrahamowicz, M., Esdaile, JM., Ramsey-Goldman, R., et al.[2019]

In a study of 71 patients with proliferative lupus nephritis, short-term high-dose intravenous cyclophosphamide followed by mycophenolate mofetil effectively prevented renal relapses, end-stage renal disease, and mortality over a median follow-up of 3.8 years.

The treatment also significantly improved disease activity and health-related quality of life, as evidenced by reductions in disease markers and improvements in patient-reported outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction therapy with short-term high-dose intravenous cyclophosphamide followed by mycophenolate mofetil in proliferative lupus nephritis. Arends, S., Berden, JH., Grootscholten, C., et al.[2017]

In a study of 67 patients with lupus nephritis receiving intravenous cyclophosphamide (IVCY), the overall remission rate was 78%, with patients experiencing fresh nephritis (Group A) showing significantly higher remission rates compared to those with relapse or transitional nephritis.

The study found that while combining steroid pulse therapy with IVCY improved remission rates in Group A, it did not affect the maintenance of remission, and there were no late-onset adverse effects associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-term prognosis of lupus nephritis patients treated with intravenous cyclophosphamide. Matsuyama, N., Morimoto, S., Tokano, Y., et al.[2019]

A 36-month treatment with intravenous cyclophosphamide (IVCY) in 16 children with lupus nephritis significantly reduced renal biopsy activity, indicating improved kidney health (activity index decreased from 9 to 1).

The therapy also led to better overall disease control, as shown by a significant drop in SLEDAI scores and a reduction in prednisone dosage by over 50%, with no significant complications reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent intravenous cyclophosphamide arrests progression of the renal chronicity index in childhood systemic lupus erythematosus. Lehman, TJ., Onel, K.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06255028

NCT06255028 | A Study of CNTY-101 in Participants With ... CALiPSO-1 is a Phase 1, multi-centre, dose-confirmation study to evaluate the safety and efficacy of CNTY-101 in participants with refractory B cell-mediated ...

2. investors.centurytx.com investors.centurytx.com/news-releases/news-release-details/century-therapeutics-announces-investigator-initiated-phase-12

Century Therapeutics Announces Investigator-Initiated ... The IIT (known as the CARAMEL trial) will evaluate safety, efficacy, and key translational data of CNTY-101 in systemic lupus erythematosus, lupus nephritis, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11893482/

Comparative Efficacy of Immunosuppressive Therapies in the ... Our findings robustly support routine use of MMF in dcSSc and show benefit especially in early‐stage disease.

4. investors.centurytx.com investors.centurytx.com/news-releases/news-release-details/century-therapeutics-reports-third-quarter-2024-financial

Century Therapeutics Reports Third Quarter 2024 ... As of the data snapshot October 15, 2024, eight additional participants have been treated with CNTY-101 for a total of 20 participants evaluable ...

5. trial.medpath.com trial.medpath.com/news/40c9f7efeaa1b896/century-therapeutics-advances-autoimmune-disease-treatment-with-phase-1-2-trial-of-ipsc-derived-cnty-101

Century Therapeutics' CNTY-101 to be Evaluated ... - MedPath The study aims to assess the safety, efficacy, and translational data of CNTY-101 in systemic lupus erythematosusSearch disease (SLE), lupus nephritisSearch ...

6. delta.larvol.com delta.larvol.com/Products/?ProductId=16b2d28d-7737-4694-b756-8fbc072ba5f4

CNTY-101 / Century Therap CNTY-101 in Autoimmune Diseases (GlobeNewswire) - "CALiPSO-1 trial progressing with continued patient enrollment and clinical trial site activations.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04166552

Study Details | NCT04166552 | Evaluation of Safety, ... The purpose of this trial is to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of EHP-101 in adult subjects with diffuse ...