Evaluate long-term safety, tolerability and efficacy of iptacopan in study participants with aHUS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

8 Jan 2025 → ongoing

Decision date (initial)

2024-10-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2022-502965-34-00

ClinicalTrials.gov

NCT05795140

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Others

To evaluate the long-term safety and tolerability of iptacopan in study participants with aHUS

Secondary objectives 5

1. - To evaluate the proportion of participants free of thrombotic microangioathy (TMA) manifestation yearly throughout the study.
2. To assess the proportion of participants treated with iptacopan who meet complete TMA response criteria over time
3. To assess the effect of iptacopan study treatment on estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) stage
4. To assess the effect of iptacopan study treatment on dialysis requirement status
5. To evaluate proportion of participants with Thrombotic Microangiopathy (TMA) related events

Conditions and MedDRA coding

Atypical Hemolytic Uremic Syndrome (aHUS)

Regulatory references

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Signed informed consent must be obtained prior to participation in the open label extension study
2. Willing and able to comply with the study Schedule of Activities (Section 1.3 of the protocol)
3. Participants who have completed the full study treatment period of any prior "Novartis sponsored" iptacopan Phase 3 clinical trial in aHUS (e.g. CLNP023F12301, CLNP023F12302) are still on iptacopan study treatment and derive benefit from it as per Investigator's judgement
4. Prior vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections should be up to date (i.e. any boosters required should be administered according to local guidelines)

Exclusion criteria 6

1. Concomitant treatment with any complement inhibitor as well as concomitant treatment with any of the drugs listed in Section 6.8.2
2. Any comorbidity or medical condition (including but not limited to any active systemic bacterial, viral or fungal infection or malignancy) that, in the opinion of the Investigator could put the participant at risk
3. Active infection or history of recurrent invasive infections caused by encapsulated bacteria such as Neisseria meningitidis, Streptococcus pneumoniae or Haemophilus influenzae
4. History of hypersensitivity to iptacopan or its excipients or to drugs of similar chemical classes
5. Pregnant or nursing (lactating) women
6. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of investigational drug and for 1 week after stopping of investigational drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety evaluations including adverse events (AE) /serious adverse events (SAE), safety laboratory parameters, vital signs and electrocardiograms (ECGs) through study duration.

Secondary endpoints 5

1. Absence of TMA manifestation without use of anti-C5 antibody throughout the study. TMA manifestation defined by the coexistence of min. two of the three criteria at the same visit attributable to aHUS: ● thrombocytopenia (platelet count decrease of ≥ 25% compared to baseline and < LLN), ● microangiopathic hemolytic anemia (hemoglobin ≤ LLN for age and gender and LDH ≥ 1.5 x ULN), ● worsening kidney function (serum creatinine increase of >25% compared to baseline levels)
2. Complete TMA response status without the use of anti-C5 antibody therapy through study duration. Complete TMA Response is defined as: hematological normalization in platelet count (platelet count ≥150 x 109 /L) and LDH (below ULN), and improvement in kidney function (≥ 25% serum creatinine reduction from baseline or ≥ 25% serum creatinine reduction compared to serum creatinine values prior to initiation of anti-C5 antibody therapy)
3. Observed value and change from baseline in eGFR and CKD stage (1-5) based on eGFR categories through study duration
4. Dialysis requirement status through study duration
5. TMA related events during the study defined as any of the following: ● Irreversible (>3 months) reduction in eGFR rate by ≥20%, not attributable to another cause ● An episode of acute kidney injury (AKI) attributed to a TMA that requires renal replacement therapy ● A non-renal manifestation of a TMA that requires hospitalization or causes irreversible organ damage or death

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 4

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications