CNTY-101 for Lupus

(CALiPSO-1 Trial)

Recruiting at4 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Century Therapeutics, Inc.

Disqualifiers: Hemodialysis, CNS disease, Transplant, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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 autoimmune diseases including those with moderate to severe systemic lupus erythematosus (SLE) with or without lupus nephritis (LN), idiopathic inflammatory myopathies (IIM), and diffuse cutaneous systemic sclerosis (DcSSc).

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.

What data supports the effectiveness of the drug CNTY-101 for treating lupus?

Research shows that cyclophosphamide, a component of the treatment, has been effective in treating lupus nephritis, a kidney condition related to lupus, by improving disease parameters and quality of life. This suggests that the treatment may have potential benefits for lupus patients. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• CNTY-101 (Monoclonal Antibodies)
• IL-2 (Cytokine)
• Lymphodepleting Chemotherapy (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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

1. Germany 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. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Induction therapy with short-term high-dose intravenous cyclophosphamide followed by mycophenolate mofetil in proliferative lupus nephritis. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

Intermittent intravenous cyclophosphamide arrests progression of the renal chronicity index in childhood systemic lupus erythematosus. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Development and Validation of a Novel Evidence-Based Lupus Multivariable Outcome Score for Clinical Trials. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

The long-term prognosis of lupus nephritis patients treated with intravenous cyclophosphamide. [2019]