Our findings emphasized that the combinatorial therapy of sericin and HQ could orchestrate the PI3K/Akt/Nrf2/NF-κB signaling pathway in the lungs, counteracting oxidative stress, inflammation, and uncontrolled cellular proliferation and sustaining lung structures. Furthermore, they could serve as anticancer agents, hindering lung cancer progression.

P2, N=187, Completed, Milton S. Hershey Medical Center | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> Jun 2024

P=N/A, N=294, Not yet recruiting, University of Sao Paulo

P=N/A, N=81, Completed, University of Leeds | Recruiting --> Completed | N=250 --> 81 | Trial completion date: Jul 2025 --> Jul 2024

This study reveals that CD147 internalization and CD147-G3BP1 complex translocation to lysosomes induce cytoprotective autophagy, reducing chemotherapy sensitivity by suppressing mTOR activity. It is also shown that chemotherapy drugs combined with autophagy inhibitors can improve the therapeutic effect of cancer, providing new insights into potential targeted therapeutic approaches in treating HCC.

The findings of our research suggest that hydroxychloroquine may be used as a potential therapeutic agent in the treatment of sepsis. Hydroxychloroquine may have an important effect in the pathogenesis of sepsis-associated CINM by reducing cytokine production and oxidative stress.

P2, N=211, Completed, Edesa Biotech Inc. | Active, not recruiting --> Completed | N=126 --> 211

P4, N=58, Completed, Guizhou Provincial People's Hospital (Single center research); Guizhou Provincial People's Hospital

P2, N=300, Recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Feb 2024 --> Apr 2025

P3, N=60, Recruiting, University of California, San Francisco | Trial completion date: Jul 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jul 2025

The findings from this study offered robust evidence supporting the use of hydroxychloroquine as a treatment for non-small cell lung cancer (NSCLC). Consequently, hydroxychloroquine emerges as a potential therapeutic agent for the treatment of this cancer.

P=N/A, N=796, Not yet recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

She was diagnosed with rheumatoid arthritis with Castleman like histopathology in lymph nodes and was treated with methotrexate and hydroxychloroquine sulfate combined with glucocorticoids. In the first year after sur-gery, the patient' s condition remained stable and there was no growth of lymph nodes in the right axilla. The patient passed away due to severe infection in the second year after the surgery.

P2/3, N=200, Recruiting, Tongji Hospital | Trial completion date: Jun 2025 --> Nov 2025 | Trial primary completion date: Jun 2024 --> Sep 2024

Rbbp6 overexpression similarly suppressed inflammatory activation of RAW264.7 cells, which was counteracted by Pla2g7 or Spi1 upregulation. In summary, this study demonstrates that the Pla2g7 loss and Spi1 upregulation participate in inflammatory responses in sepsis by elevating the Lp-PLA2 levels.

P2/3, N=10, Terminated, Columbia University | N=1600 --> 10 | Recruiting --> Terminated; The Institutional Review Board closed the study

P2, N=600, Active, not recruiting, ProgenaBiome | Recruiting --> Active, not recruiting | Phase classification: P2a --> P2 | Trial completion date: Jul 2025 --> Dec 2024

P=N/A, N=188, Not yet recruiting, Dongzhimen Hospital, Beijing University of Chinese Medicine; Dongzhimen Hospital, Beijing University of Chinese Medicine

P=N/A, N=65, Terminated, University of California, San Francisco | Trial completion date: Feb 2025 --> Feb 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2025 --> Feb 2024; Study investigators became aware of an internal error that overrode randomization of providers; therefore, the study randomization for this study was no longer present.

These findings support that HCQ plays a role in the treatment of mice colitis possibly by altering the gut microbiota.

In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA.

A double-blind multicenter study of adults with active Crohn's disease, (i.e., Crohn's Disease Activity Index [CDAI] 220-450 plus C-reactive protein ≥ 1.0 mg/dL, fecal calprotectin (FCP) >162.9 µg/g stool, or recent endoscopic or radiographic confirmation of active disease) receiving concomitant standard-of-care Crohn's disease treatment (Clinicaltrials.gov: NCT01951326) were stratified by anti-tumor necrosis factor use and randomized (1:1) to anti-MAP RHB-104 (clarithromycin 95 mg, rifabutin 45 mg, and clofazimine 10 mg per capsule) (n = 166), resulting in clarithromycin 950 mg/day, rifabutin 450 mg/day, and clofazimine 100 mg/day, or placebo (n = 165) for up to 52 weeks. No patient died during the study. Antimicrobial therapy directed against MAP resulted in significantly greater improvement in clinical and laboratory (FCP) measures of active Crohn's disease.

The autophagy inhibition of HFn@HCQ has been demonstrated, which is a major pathway to induce cancer cell death. According to current findings, HFn based drug delivery is a promising strategy to target and kill TfR1 overexpressing tumor cells.

P=N/A, N=50, Recruiting, University Hospital, Toulouse | Trial completion date: May 2024 --> Dec 2024 | Trial primary completion date: May 2024 --> Dec 2024

Simultaneously, in order to refrain from mitophagy, hydroxychloroquine is mixed with NBE to form a combo with strength pyroptosis. As a result, NBE/combo improves the PAFerroptosis obviously by activation of CD8+T cells and inactivation of MDSC cells, up-regulating expression of caspase-3 signal pathway, intercepting DHODH pathway to arrive excellent antitumor effect (93%). Therefore, this study establishes a rational nanoenzyme for mitochondrial dysfunction without mitophagy for effective antitumor therapy.

P1, N=20, Not yet recruiting, Lionel.D.Lewis, MD | Initiation date: Jun 2024 --> Sep 2024

P4, N=24, Terminated, Duke University | Active, not recruiting --> Terminated; Showed no benefit

P1/2, N=31, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

After internalization and lysosomal escape, the nanoparticle disassembles in response to the reactive oxygen species (ROS), subsequently releasing the iron chelator Dp44mT and autophagy-inhibitory drug hydroxychloroquine (HCQ)...Consequentially, Dp44mT@HTH induces irreversible mitochondrial impairments, in this respect creating a substantial toxic stack state that induces apoptosis and cell death. Initiating from the perspective of endogenous substances, this strategy illuminates the promise of iron depletion therapy via irreversible mitochondrial damage induction for anticancer treatment.

P2, N=64, Active, not recruiting, The University of Texas Health Science Center at San Antonio | Recruiting --> Active, not recruiting | Trial completion date: Mar 2025 --> Jun 2025 | Trial primary completion date: Mar 2024 --> Jun 2025

P4, N=25, Recruiting, Alimera Sciences

A hydroxychloroquine (HCQ) platinum(IV) complex with autophagy suppressing potency was developed, which displayed potent antitumor activities with a TGI rate of 44.2% against 4T1 tumors in vivo and exhibited a rather lower toxicity than cisplatin. Adaptive immune response was improved by inhibiting the immune checkpoint PD-L1 and further increasing CD4+ and CD8+ T cells in tumors. Then, tumor metastasis was effectively inhibited by restraining angiogenesis through inhibiting VEGFA, MMP-9, and CD34.

Then, the thermosensitive liposome modified with FAP-α-responsive peptide (CAP) was used as a carrier to encapsulate autophagy inhibitor hydroxychloroquine (HCQ) and Tf-Te, to obtain an intelligent TT@CH delivery system...Meanwhile, lung metastatic nodules of TT@CH treated mice reduced by 124.33 compared with that of mice in control group. Overall, TT@CH provided an effective therapy strategy for melanoma.

Most importantly, PLAG4B was independently related to longer disease-free survival. This is the first study exploring comprehensively the expression levels of PLA2 in PCa, showing that the higher expression of some PLA2 should be used as biomarkers of good prognosis and longer disease-free survival.

P2, N=334, Not yet recruiting, Centre Hospitalier Universitaire de Saint Etienne | Initiation date: Jun 2024 --> Sep 2024

P=N/A, N=140, Recruiting, King's College Hospital NHS Trust | Not yet recruiting --> Recruiting | Trial completion date: Nov 2025 --> May 2026 | Trial primary completion date: Nov 2025 --> May 2026

P=N/A, N=56, Recruiting, Erasmus Medical Center

P=N/A, N=315, Completed, Erasmus Medical Center

P3, N=60, Recruiting, University of California, San Francisco | Not yet recruiting --> Recruiting

P3, N=234, Recruiting, Mannkind Corporation | Not yet recruiting --> Recruiting

P4, N=43, Active, not recruiting, Guy's and St Thomas' NHS Foundation Trust | Recruiting --> Active, not recruiting | N=76 --> 43 | Trial primary completion date: Sep 2024 --> May 2025

P2, N=140, Recruiting, Ophirex, Inc. | Trial completion date: Dec 2024 --> Jul 2025 | Trial primary completion date: Dec 2024 --> Mar 2025