Study of efficacy and safety of iptacopan in complement 3 glomerulopathy patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

28 Jul 2021 → ongoing

Decision date (initial)

2024-07-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-509331-83-00

EudraCT number

2020-004589-21

ClinicalTrials.gov

NCT04817618

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy, Pharmacodynamic

Primary objective in adult participants:
To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria.

Primary objective in adolescent participants:
To evaluate the effect of iptacopan on proteinuria at 6 months.

Secondary objectives 9

1. Secondary objectives for adult participants: - To demonstrate the superiority of iptacopan vs. placebo in improving eGFR.
2. Secondary objectives for adult participants: - To demonstrate the superiority of iptacopan vs. placebo in the proportion of participants who achieved a composite renal endpoint.
3. Secondary objectives for adult participants: - To demonstrate the effect of iptacopan vs placebo in reducing glomerular inflammation in the kidney.
4. Secondary objectives for adult participants: - To assess the effect of iptacopan compared to placebo in improvement of patient reported fatigue.
5. Secondary objectives for adult participants: - To evaluate the safety and tolerability of iptacopan compared to placebo.
6. Secondary objectives in adolescent participants: - To evaluate the effect of iptacopan in improving eGFR.
7. Secondary objectives in adolescent participants: - To evaluate the effect of iptacopan on a composite renal endpoint.
8. Secondary objectives in adolescent participants: - To evaluate the effect of iptacopan in improvement of patient-reported fatigue.
9. Secondary objectives in adolescent participants: - To evaluate the safety and tolerability of iptacopan compared to placebo during the 6-month double-blind period.

Conditions and MedDRA coding

complement 3 glomerulopathy

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002705-PIP01-19

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 9

1. Male and female participants age ≥ 18 and ≤ 60 years (adult cohort) or age ≥ 12 and ≤ 17 years (adolescent cohort) at screening.
2. Diagnosis of C3G as confirmed by renal biopsy within 12 months prior to screening in adults and within 3 years of screening in adolescents (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available, confirmation may be obtained using tissue from the Day -45 biopsy (adults only) for local assessment (tissue may be processed, evaluated, and reported by Arkana Laboratories but eligibility is determined by the Investigator).
3. Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of renin-angiotensin system inhibitors (RASi), e.g., an angiotensin converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) for at least 90 days. The doses of other antiproteinuric medications including mycophenolic acids, corticosteroids, and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization.
4. Reduced serum C3 (defined as less than 0.85 x lower limit of the central laboratory normal range) at Screening.
5. UPCR ≥ 1.0 g/g sampled from the first morning void urine sample at Day -75 and Day -15.
6. Estimated GFR (using the CKD-EPI formula for adults and modified Schwartz formula for adolescents) or measured GFR ≥ 30 ml/min/1.73m2 at Screening and Day -15.
7. Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, the vaccine should be given according to local guidelines at least 2 weeks prior to the first administration of study treatment. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
8. Vaccination against Haemophilus influenzae infections is recommended according to local guidelines, at least 2 weeks prior to the first study treatment administration.
9. In Germany only, adolescent participants must also have reached Tanner stage IV or V at the Screening visit to be enrolled in the study.

Exclusion criteria 9

1. Participants who have received any cell or organ transplantation, including kidney transplantation.
2. Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with renal biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli.
3. Renal biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%.
4. Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care.
5. Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration or the presence of fever ≥ 38°C (100.4°F) within 7 days prior to study treatment administration.
6. A history of recurrent invasive infections caused by encapsulated organisms, e.g., meningococcus or pneumococcus.
7. The use of inhibitors of complement factors (e.g., Factor B, Factor D, C3 inhibitors, anti Complement component 5 (C5) antibodies, C5a receptor antagonists) within 6 months prior to the Screening visit.
8. The use of immunosuppressants (except mycophenolic acids), cyclophosphamide or systemic prednisone at a dose >7.5 mg/day (or equivalent for a similar medication) within 90 days of study drug administration. The use of mycophenolic acids is not permitted within 90 days prior to randomization in India.
9. Acute post-infectious glomerulonephritis at screening based upon the opinion of the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint for adult participants: - Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection) Primary endpoint for adolescent participants: - Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection).

Secondary endpoints 9

1. Secondary endpoint for adult participants: - Change from baseline in eGFR.
2. Secondary endpoint for adult participants: - A participant meets the requirements of the composite renal endpoint if he/she satisfies: (1) a stable or improved eGFR compared to the baseline visit (≤15% reduction in eGFR), and (2) a ≥50% reduction in UPCR compared to the baseline visit.
3. Secondary endpoint for adult participants: - Change from baseline in disease total activity score in a renal biopsy.
4. Secondary endpoint for adult participants: - Change in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT Fatigue) score.
5. Secondary endpoint for adult participants: - Occurrence of clinically significant vital signs (msDBP, msSBP, heart rate), ECGs, and safety laboratory measurements, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE.
6. Secondary endpoint for adolescent participants: - Change from baseline in eGFR.
7. Secondary endpoint for adolescent participants: - A participant meets the requirements of the composite renal endpoint if he/she satisfies the following criteria at the 6-month time point: (1) a stable or improved eGFR compared to the baseline visit (≤15% reduction in eGFR), and (2) a ≥50% reduction in UPCR compared to the baseline visit.
8. Secondary endpoint for adolescent participants: - Change from baseline to 6 months in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.
9. Secondary endpoint for adolescent participants: - Occurrence of clinically significant vital signs, ECGs, and safety laboratory measurements, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE (or any safety issue) during the double-blind period of the study.

Investigational products

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

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

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 18

Locations

7 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 81 files

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

Application history

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